Diaminotriazoles, suitable as inhibitors of protein kinases

FIELD: medicine.

SUBSTANCE: formula bond

or it pharmaceutically comprehensible salt where value of radicals are specified in the invention formula is described. The bonds are effective as inhibitors of protein kinases FLT-3 or KIT. A way of inhibition of activity kinases FLT-3 or KIT in the biological sample in vitro and application of bonds for manufacture of a medical product, suitable for treatment or simplification of gravity of disease or a condition, the chosen acute myelogenetic leukosis, acute progranulocytic leukemia or acute lymphocytic leukosis or cancer of ovaries are described also.

EFFECT: rising of efficiency of a composition and the method of treatment.

11 cl, 86 ex

 

In the present application claims priority under 35 U.S.C. § 119 provisional applications U.S. number 60/426681 registered November 15, 2002 and entitled "Compositions Useful as Inhibitors of Protein Kinase", and 60/447705, registered on February 11, 2003 and entitled "Compositions Useful as Inhibitors of Protein Kinase", and the full content of each of these applications, therefore, included as a reference.

The present invention relates to inhibitors of protein kinases. The invention relates also to pharmaceutical compositions containing compounds of the invention and methods of using the compositions in the treatment of various diseases.

The search for new therapeutic agents has helped considerably in recent years a better understanding of the structure of enzymes and other biomolecules associated with diseases. One important class of enzymes that have been the subject of extensive research, are protein kinases.

Protein kinases constitute a large family of structurally close enzymes, which are responsible for the control of various processes of signal transduction in the cell. (See Hardie, G. and Hanks, S. The Protein Kinase Facts Book, I and II, Academic Press, San Diego, CA: 1995). It is believed that protein kinases have emerged out of the ordinary ancestral gene due to conservation of their structure and catalytic function. Almost all kinases contain similar kata is eticheski domain of 250-300 amino acids. Kinases can be grouped into classes on the substrates they phosphorylate (e.g., proteinkinases, proteinsin/threonine, lipids and the like). The identified sequence motifs, which typically correspond to each of these families of kinases (see, for example, Hanks, S.K. Hunter, T., FASEB J. 1995, 9, 576-596; Knighton et al., Science, 1991, 253, 407-414; Hiles et al., Cell 1992, 70, 419-429, Kunz et al., Cell 1993, 73, 585-596; Carcia-Bustos et al., EMBO J. 1994, 13, 2352-2361).

In General, protein kinases mediate intracellular signal transmission effect transfer of phosphoryla from nucleosidase to the acceptor-protein, which is involved in the migration paths of the signal. These phenomena phosphorylation act as molecular inclusions/off, which can modulate or regulate the biological function of the target protein. These phosphorylation events eventually triggered in response to various extracellular and other incentives. Examples of such incentives include signals stresses environmental and chemical stress (e.g., osmotic shock, heat shock, ultraviolet radiation, bacterial endotoxin, and N2About2), cytokines (e.g. interleukin-1 (IL-1) and factor α tumor necrosis (TNF-α)) and growth factors (for example, the cofactor of colony-granulocyte-macrophage (GM-CSF), and fibroblast growth factor (FGF)). Uncle cnie incentives can act on one or more cellular responses, related to growth, migration, cell differentiation, hormone secretion, activation of transcription factors, muscle contraction, glucose metabolism, regulation of protein synthesis and cell cycle regulation.

Many diseases are associated with abnormal cellular responses triggered mediated by protein kinases events, as described above. These diseases include, but are not limited to, autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies and asthma, Alzheimer's disease and hormone-related diseases. In accordance with this significant efforts in medicinal chemistry focused on finding inhibitors of protein kinases, which are effective as therapeutic agents.

Family of receptor type III tyrosinekinase, including Flt3, c-Kit, PDGF-receptor and c-Fms, plays an important role in the preservation, growth and development of hematopoietic and megamarketinc cells [Scheijen, B, Criffin JD, Oncogene, 2002, 21, 3314-3333 and Reille, JT, British Journal of Haematology, 2002, 116, 744-757]. FLT-3 and C-Kit regulate the conservation pools of stem cells/early progenitor cells, and the development of Mature lymphoid and myeloid cells [Lyman, S. Jacobsen, S, Blood, 1998, 91, 1101-1134]. Both PE is aptara contain inherent domain of the kinase, which is activated when mediated by the ligand of receptor dimerization. When the activation domain of the kinase induces autophosphorylation of the receptor and phosphorylation of various cytoplasmically proteins, which help to spread the activation signal, resulting in growth, differentiation and survival. Some of transmitting a signal of negative regulators of FLT-3 and C-Kit include PLCγ, PI3-kinase, Grb-2, SHIP and Sre related kinase [Scheijen, B. Griffin, JD, Oncogene, 2002, 21, 3314-3333]. Found that both receptor tyrosine kinase play a role in various hematopoietic and megamarketinc tumors. Mutations that induce ligandability activation of FLT-3 and c-Kit, are involved in acute myelogenous leukemia (AML), acute linfocitos leukemia (ALL), mastocytosis and tumor gastrointestinal stromal (GIST). These mutations include single amino acid change in the kinase domain or internal tandem duplications, point mutations or deletions in the reading frame located near the region of membrane receptors. In addition to activating mutations lanzavecchia (autocrine or paracrine) stimulation sverkhekspressiya FLT3 wild-type or c-Kit may contribute to the malignant phenotype [Scheijen, B. Griffin JD, Oncogene, 2002, 21, 3314-3333].

C-fms encodes the receptor for colony stimulating factor macrophage (M-CSF-1R), to the which is expressed mainly in the line of differentiation of monocytes/mariahof [Dai, XM et al., Blood, 2002, 99, 111-120]. M-CSF-1R and its ligands regulate line growth and differentiation of macrophages. Like other members of the family of M-CSF-1R contains the inherent domain of the kinase, which is activated by ligand-induced dimerization of the receptor. M-CSF-1R is expressed in megamarketinc cells, including epithelial cells of the mammary gland and neurons. Mutations in this receptor are potentially associated with myeloid leukemia and its expression correlates with metastatic carcinoma of the breast, ovary and endometrium ['reilly, JT, British Journal of Haematology, 2002, 116, 744-757 and Kacinski, BM, Mol. Reprod. and Devel., 1997, 46, 71-74]. Another possible indication for antagonists of M-CSF-1R is osteoporosis [Teitelbaum, S., Science 2000, 289, 1504-1508].

PDGF-receptor (DERIVED) has two subunits, DERIVED-α and DERIVED-βthat can form Homo - or heterodimer when the binding of the ligand. There are several ligands DERIVED: AB, BB, CC and DD. DERIVED is expressed on early stem cells, mast cells, myeloid cells, mesenchymal cells and smooth muscle cells [Scheijen, B. Griffin, JD, Oncogene, 2002, 21, 3314-3333]. Only DERIVED-β involved in myeloid leukemia, usually as a translocation partner with Tel, protein interaction Huntington (HIP1) or rebaptism 5. Recently it was discovered that activating mutations in the kinase domain DERIVED-α occurs in tumors gastrointestinal stromal (GIST) [Heirich, MC et al., Sciencexpress, 2003].

Cyclin-dependent kinases (CDKs) are serine/trainingmaterial consisting of enriched β-fold aminocentesis and a large share of carboxykinase share, which is basically α-spiral. CDKs detects 11 subdomains involved in all protein kinases and having the range of molecular masses from 33 to 44 KD. This family of kinases, which includes CDK1, CDK2, CDK4 and CDK6, requires phosphorylation at the residue corresponding to Thr 160 CDK2 to be fully active [Meijer, L., Drug Resistance Updates 2000, 3, 83-88].

Each CDK complex is formed from a regulatory subunit cyclina (for example, cyclina a, B1, B2, D1, D2, D3 and E) and catalytic subunit of the kinase (such as CDK1, CDK2, CDK4, CDK5 and CDK6). Each different pair kinase/cyclin operates to regulate different and specific phases of the cell cycle, known as phases G1, S, G2 and M [Nigg, E., 2001 Nature Reviews, 2, 21-32; Flatt, P., Pietenpol, J. Drug Metabolism Reviews 2000, 32, 283-305].

CDKs are involved in disorders of cell proliferation, especially in cancer. Cell proliferation is a result of direct or indirect deregulation of the division cell cycle, CDKs plays a critical role in the regulation of various phases of this cycle. For example, overexpression of cycline D1 is usually associated with various cancer diseases, including carcinomas and gliomas, breast cancer, colon Ki is Ki and hepatocellular carcinoma and glioma [Flatt, P., Pietenpol, J., Drug Metabolism Rewiews 2000, 32, 283-305]. The complex CDK2/cyclin E plays a key role in the development from early phase G1prior to the S phase of the cell cycle, and overexpression of cycline E has been associated with various solid tumors. Therefore, inhibitors of tsiklonov D1, E, or their associated CDKs are suitable targets for cancer therapy [Kaubisch, A. Schwartz, G., The Cancer Journal 2000, 6, 192-212].

CDKs, especially CDK2, also plays a role in apoptosis and the development of T cells. CDK2 was identifitsirovan as a key regulator of apoptosis thymocyte [Williams, O., et al., European Journal of Immunology 2000, 709-713]. Stimulation of the activity of CDK2-kinase associated with the development of apoptosis in thymocytes in response to specific stimuli. Inhibition of the activity of CDK2-kinase blocks the apoptosis that leads to the protection of thymocytes.

In addition to cell cycle regulation and apoptosis CDKs are directly involved in the transcription process. Different viruses CDKs require for their replication process. Examples in which the CDK inhibitors limit viral replication include cytomegalovirus human herpes virus and varicella zoster virus [Meijer, L., Drug Resistance Updates 2000, 3, 83-88].

Inhibition of CDK is also suitable for the treatment of neurodegenerative disorders, such as Alzheimer's disease. The appearance of paired helical filaments (PHF), associated with Alzheimer's disease, called the ISU is fosfaurilirovaniem Tau protein CDK5/P25 [Meijer, L., Drug Resistance Updates, 2000, 3, 83-88].

Another particularly interesting family of kinases is the family of Src kinases. These kinases involved in cancer, immune dysfunction and resurfacing bone diseases. For General surveys, see Thomas and Brugge, Annu. Rtv. Cell Dev. Biol. 1997, 13, 513; Lawrence and Niu, Pharmacol. Ther. 1998, 77, 81; Tatosyan and Mizenina, Biochemistry (Moscow), 2000, 65, 49; Boschelli et al., Drugs of The Future 2000, 25(7), 717, (2000).

Members of the Src family include the following eight kinases in mammals: Src, Fyn, Yes, Fgr, Lyn, Hck, Lck and Blk. These preceptory protein kinases have a range of molecular weights from 52 to 62 KD. All of them are characterized by the General structural organization, which consists of six specific functional domains: the domain of Src homology 4 (SH4), a unique domain, SH3 domain, SH2 domain, a catalytic domain (SH1) and C-terminal regulatory region. Tatosyan et al. Biochemistry (Moscow), 2000, 65, 49-58.

Based on published studies of Src kinase considered as potential therapeutic targets for various diseases. Mice that lack in Src, characterized by the development of osteoporosis or build bones due to low bone resorption by osteoclasts. This suggests that osteoporosis resulting from abnormally high bone resorption, can be treated by inhibition of Src. Soriano et al., Cell 1992, 69, 551 and Soriano et al., Cell 199, 64, 693.

Suppression of destruction of arthritic bones was achieved by overexpression of CSK in rheumatoid synoviocytes and osteoclasts. Takayanagi et al., J. Clin Invest. 1999, 104, 137. CSK or C-terminal Src kinase phosphorylates and thereby inhibits the catalytic activity of Src. This means that inhibition of Src can prevent the degradation of the joint, which is characteristic of patients suffering from rheumatoid arthritis. Boschelli et al., Drugs of the Future 2000, 25(7), 717.

Src also plays a role in viral replication of hepatitis C. virus Encoded transcription factor NVH activates Src in stages required for propagation of the virus. Klein et al., EMBO J. 1999, 18, 5019 and Klein et al., Mol. Cell. Biol. 1997, 17, 6427.

Several studies have linked the expression of Src with cancer, such as colon cancer, breast cancer, liver and pancreas, certain b-cell leukemias and lymphomas. Talamontiet al., J. Clin. Invest.1993,91,53; Lutzet al., Biochem. Biophys. Res.1998243,503; Rosenet al., J. Biol. Chem.1986,261,13754; Bolenet al., Proc. Natl. Acad. Sci. USA1987,84,2251; Masakiet al., Hepatology1998,27,1257; Biscardiet al., Adv. Cancer Res.1999,76,61; Lynchet al., Leukemia, 1993, 7, 1416.In addition, it was found that antisense Src, expressed in the tumor cells of the ovaries and rectum, inhibits tumor growth. Wiener et al., Clin Cancer Res., 1999, 5, 2164; Staley et al., Cell Growth Diff., 1997, 8, 269.

Other kinase families who STV Src are also potential therapeutic targets. Lck plays a role in signaling T cells. A mouse lacking the gene Lck, have a weak ability to develop tomatito. The Lck function as a positive activator of the transmission signal T cells confirms that inhibitors of Lck may be applicable for the treatment of autoimmune diseases such as rheumatoid arthritis. Molina et al., Nature, 1992, 357, 161. Hck, Fgr and Lyn have been identified as important mediators of signal transmission integrin in myeloid leukocytes. Lowell et al., J. Leukoc. Biol., 1999, 65, 313. Inhibition of these mediators kinase may therefore be useful for treatment of inflammation. Boschelli et al., Drugs of the Future 2000, 25(7), 717.

Syk is a receptor that plays a critical role in mediated FcεRI degranulation of mast cells and activation of eosinophils. In accordance with this kinase Syk is involved in various allergic disorders, in particular asthma. It was found that Syk binds to phosphorylated gamma chain of Fc receptorεRI through the N-terminal SH2 domains and is essential for subsequent transmission of the signal [Taylor et al., Mol. Cell. Biol. 1995, 15, 4149].

Inhibition of apoptosis of eosinophils was proposed as a key mechanism for the development of eosinophilia in the blood and tissues in asthma. IL-5 and GM-CSF positively regulated in asthma and are offered for the induction of eosinophilia in the blood and tissues ing is the repression of apoptosis of eosinophils. Inhibition of apoptosis of eosinophils was proposed as a key mechanism for the development of eosinophilia in the blood and tissues in asthma. Indicates that the kinase Syk is required for prevention of apoptosis of eosinophils cytokines (using antisense sequences) [Yousefi et al., J. Exp Med 1996, 183, 1407].

The role of Syk in FcγR-dependent and-independent responses in bone-marrow-derived macrophages was determined using irradiated mouse chimeras, reconstructed cells derived from fetal liver of Syk-/-embryos. SYK-deficient macrophages were defective in phagocytosis induced by FcγR, but showed normal phagocytosis in response to the complement [Kiefer et al., Mol Cell Biol. 1998, 18, 4209]. It was also noted that the antisense sequence harrisoniana Syk suppresses the expression of Syk and releases the mediator of macrophage (Stenton et al., Immunology 2000, 164, 3790].

The Janus kinase (JAK) are a family consisting of JAK1, JAK2, JAK3 and TYK2. JAK play a critical role in the signaling of cytokines. Subsequent downstream events substrates family kinases JAK include transducer signal and activator protein transcription (STAT). Signaling JAK/STAT is involved in mediating many abnormal immune responses such as allergies, asthma, autoimmune diseases such as transplant rejection, rheumatoid arthritis, side is howling amyotrophic sclerosis and multiple sclerosis, as well as solid and hematological malignancy, such as leukemia and lymphoma. Pharmaceutical intervention in the path of the JAK/STAT indicated in the reviews [Frank Mol. Med. 5, 432-456 (1999) & Seidel et al., Oncogene 19, 2646-2656 (2000)].

JAK1, JAK2 and TYK2 are expressed ubiquitously, whereas Jak3 is predominantly expressed in hematopoietic cells. JAK3 is associated with exclusive gamma chain (γcregular cytokine receptor and activates IL-2, IL-4, IL-7, IL-9 and IL-15. Proliferation and survival of murine mast cells induced by IL-4 and IL-9 in fact, as we have seen, depends on the signal JAK3 and γc[Suzuki et al., Blood 96, 2172-2180 (2000)].

Binding receptors of the immunoglobulin (Ig) E with high affinity sensitized mast cells leads to the release of proinflammatory mediators, including a number of vasoactive cytokines, resulting from acute allergic or intermediate (type I) hypersensitivity reactions [Gordon et al., Nature 346, 274-276 (1990) & Galli, N. Engl. J. Med., 328, 257-265 (1993)]. Was established the critical role of JAK3 in receptor-mediated IgE responses of mast cells in vitro and in vivo [Malaviya, et al., Biochem. Biophys. Res. Commun. 257, 807-813 (1999)]. It also describes the prevention of hypersensitivity reactions type I, including anaphylaxis mediated activation of mast cells through inhibition of JAK3 [Malaviya et al., J. Biol. Chem. 274, 2702827038 (1999)]. Targeting fat cells JAK3 inhibitors modulates mast cell degranulation in vitro and prevents mediated IgE-receptor/antigen anaphylactic reactions in vivo.

In a recent study described the successful "targeting" JAK3 for immune suppression and tolerance of the allograft. The study shows the dose-dependent survival of cardiac allograft Buffalo recipients Wistar Furth with the introduction of JAK3 inhibitors, indicating the possibility of regulating unwanted immune reactions in homologous disease [Kirken Transpl. Proc. 33, 3268-3270 (2001)].

IL-4-mediated STAT-phosphorylation participated as a mechanism included in the early and late stages of rheumatoid arthritis (RA). Positive regulation of proinflammatory cytokines in the synovial membrane and synovial fluid in RA is characteristic of this disease. It was shown that IL-4-mediated activation pathway of IL-4/STAT mediated through the Janus kinase (JAK 1 & 3) and that associated with IL-4 JAK kinase is expressed in the synovial membrane of RA [Muller-Ladner, et al., J. Immunol. 164, 3894-3901 (2000)].

Family amyotrophic lateral sclerosis (FALS) is a fatal neurodegenerative disorder, affecting approximately 10% of ALS patients. The degree of survival of mice with FALS were increased in the treatment of JAK3-specific inhibitor. This item is tverdal, that JAK3 plays a role in FALS [Trieu, et al., Biochem. Biophys. Res. Commun. 267, 22-25 (2000)].

Proteins that are transduction signal and activator of transcription (STAT), are activated among other kinases of the JAK family. The results of recent studies have confirmed the possibility of interference in the transmission signal JAK/STAT via pritsenivayutsya" in the kinase family of JAK-specific inhibitors for the treatment of leukemia [Sudbeck, et al., Clin. Cancer Res. 5, 2569-1582 (1999)]. Discovered that JAR3-specific compounds inhibit count of clonogenic growth JAK3-expressing cell lines DAUDI, RAMOS, LC1; 19, NALM-6, MOLT-3 and HL-60.

In animal models of proteins merge TEL/JAK2 caused myeloproliferative disorders and in hematopoietic cell lines introduction TEL/JAK2 resulted in activation of STAT1, STAT3, STAT5 and cytokine-independent growth [Schwaller, et al., EMBO J. 17, 5321-5333 (1998)].

Inhibition of JAK3 and TYK 2 abolishes the phosphorylation of tyrosine STAT3 and inhibits the growth of cells in mycosis fungoides, a form of cutaneous lymphoma T-cells. These results imply the involvement of kinases of the JAK family in significantly activated the pathway JAK/STAT, which is present in mycosis fungoides [Neilsen, et al., Proc. Nat Acad. Sci. U.S.A. 94, 6764-6769 (1997)]. Similarly, it was shown that STAT3, STAT5, JAK1 and JAK2 significantly activated in lymphoma T-cell mice, initially characterized by overexpression of LCK, thereby further engaging way of JAK/STAT in abnormal growth of cells [Yu, et al., J. Immunol. 159, 5206-5210 (1997)]. In addition, IL-6 mediated STAT3 activation is blocked by JAK inhibitor that leads to sensitization of myeloma cells to apoptosis [Catlett-Falcone, et al., Immunity 10, 105-115 (1999)].

One of interest family kinases is Rho-associated forms handed superhelix proteinsin/trionychinae (ROCK), which is considered, is an effector of Ras-related small GTP Rho. The ROCK collection includes p160ROCK (ROCK-1) (Ishizaki et al., EMBO J 1996, 15, 1885-1893) and ROKα/Rho-kinase/ROCK-II (Leunget al., J. Biol. Chem.1995,270,29051-29054; Matsuiet al., EMBO J.1996,15,2208-2216; Nakagawaet al., FEBS Lett.1996,392,189-193), protein kinase PKN (Amanoet al., Science1996,271,648-650; Watanabeet al., Science1996,271,645-648), and citron and citrocasa (Madauleet al. Nature,1998,394,491-494; Madauleet al., FEBS Lett.1995,377,243-248). It was found that the kinase family of ROCK involved in the implementation of various functions, including Rho-induced formation of actin stress fibers and focal adhesi, (Leunget al., Mol. Cell Biol.1996,16,5313-5327; Amanoet al., Science,1997,275,1308-1311; Ishizakiet al., FEBS Lett.1997,404,118-124) and in the regulation on the type of feedback myinfosafe (Kimuraet al., Science,1996,273,245-248), activated platelets (Klages et al., J. Cell Biol., 1999, 144, 745-754), the contraction of the smooth muscle of the aorta under the influence of various stimuli (Fuet al., FEBS Lett.,1998,440,183-187), induserve the major thrombin reaction of the smooth muscle cells of the aorta, (Seasholtzet al., Cir. Res.,1999,84,1186-1193),hypertrophy of cardiomyocytes (Kuwaharaet al., FEBS Lett.,1999,452,314-318), contraction of bronchial smooth muscle (Yoshiiet al., Am. J. Respir. Cell Mol. Biol,1999,20,1190-1200), smooth muscle contraction and cytoskeletal reorganization of second cells (Fukataet al., Trends in Pharm. Sci2001,22,32-39),the activation is regulated by the amount of anionic channels (Niliuset al., J. Physiol.,1999,516,67-74),trigeminus retraction (Hirose et al., J. Cell. Biol., 1998, 141, 1625-1636), chemotaxis of neutrophils (Niggli et al,FEBS Lett.,1999,445,69-72),wound healing (Nobes and Hall, J. Cell. Biol., 144, 1235-1244), invasion of the tumor (Itohet. al., Nat. Med.,1999, 5, 221-225)and cellular transformation(Sahai trustet al., Curr. Biol,1999,9,136-145)).More specifically, the ROCK is involved in various diseases and disorders, including hypertension (Satohet al., J. Clin. Invest.1994,94,1397-1403; Mukaiet al., FASEB J.2001, 75, 1062-1064; Uehataet al., Nature1997,389,990-994; Masumotoet al., Hypertension,2001,38,1307-1310),cerebral vasospasm (Satoet al., Circ. Res.2000, 87,195-200; Miyagiet al., J. Neurosurg.2000,93,471-476; Tachibanaet al., Acta Neurochir (Wien)1999,141,13-19),coronary vasospasm (Shimokawaet al., Jpn. Cir. J.2000,64,1-12; Kandabashiet al., Circulation2000,101,1319-1323; Katsumataet al., Circulation1997,96,4357-4363; Shimokawaet al., Cardiovasc. Res.2001,51,169-177; Utsunomiyaet al., J. Pharmacol.2001,134,1724-1730; Masumotoet al., Circulation202, 105,1545-154),bronchial asthma (Chibaet al., Comp. Biochem. Physiol. C Pharmacol. Toxicol. Endocrinol.1995,11,351-357; Chibaet al., Br. J. Pharmacol.1999,127,597-600; Chibaet al., Br. J. Pharmacol.2001,133,886-890; Iizukaet al., Eur. J. Pharmacol.2000,406,273-279),premature birth (Niroet al., Biochem. Biophys. Res. Commun.1997,230,356-359; Taharaet al., Endocrinology2002,143,920-929; Kupittayanantet al., Pflugers Arch.2001,443,112-114),erectile dysfunction (Chitaleyet al., Nat. Med.2001, 7, 119-122; Millset al., J. Appl. Physiol.2001,91,1269-1273),glaucoma (Honjoet al., Arch. Ophthalmol.2001,1171-1178; Raoet al. Invest. Ophthalmol. Vis. Sci.2001,42,1029-1037),cell proliferation of vascular smooth muscle (Shimokawaet al., Cardiovasc. Res.2001,51,169-177; Morishigeet al., Arterioscler. Thromb. Vase. Biol.2001,21,548-554; Etoet al., Am. J. Physiol. Heart Circ. Physiol2000,278,H1744-H1750; Sawadaet al., Circulation2000,101,2030-2023; Shibataet al., Circulation2001,103,284-289),myocardial hypertrophy (Hoshijimaet al., J. Biol. Chem.1998,273,7725-77230; Sahet al., J. Biol. Chem.1996,271,31185-31190; Kuwaharaet al. FEBS Lett.1999,452,314-318; Yanazumeet al. J. Biol. Chem.2002,277,8618-8625),malignoma (Itohet al. Nat. Med.1999,5,221-225; Gendaet al. Hepatology1999,30,1027-1036; Somlyoet al. Biochem., Biophys. Res. Commun.2000,269,652-659),damage caused by ischemia/reperfusion (Ikedaet al. J. of Surgical Res.2003,109,155-160; Miznumaet al. Transplantation2003,75,579-586),andote the territorial dysfunction (Hernandez-Perera et al. Circ. Res.2000,87,616-622; Laufset al., J. Biol. Chem.1998,273,24266-24271; Etoet al., Circ. Res.2001,89,583-590),Crohn's disease and colitis (Segainet al. Gastroenterology2003,124(5),1180-1187),the sprouting of neurites (Fournieret al. J. Neurosci.2003,23,1416-1423),Raynaud's disease (Shimokawaet al. J. Cardiovasc. Pharmacol.2002,39,319-327) and atherosclerosis (Retzeret al. FEBS Lett.2000,466,70-74; Ishibashiet al. Biochim. Biophys. Acta2002,1590,123-130).In accordance with this development of inhibitors of kinases ROCK can be used as therapeutic agents for treating disorders involved in the way kinase ROCK.

ERK2 (kinase that regulates extracellular signal) is a member of the family of mitogen-activated protein kinases (MAR)1 mammals. Kinase (MAR)1 are serine/trionychinae, which mediate the path of intracellular signal transduction (Cobb and Goldsmith,J Biol. Chem.,1995,270,14843;Davis,Mol. Reprod. Dev.1995,42,459) and are activated by mitogens and growth factors (Bokemeyeret al. Kidney Int.1996,49,1187).Members of the family kinases MAR similarly have a common sequence and conserved structural domains and in addition ERK2 include kinase JNK (N-terminal Jun kinase) and R. Kinases JNKs and R activated in response to the proinflammatory cytokines TNF-alpha and interleukin-1 and cellular stress such as heat shock, gitarooman most, ultraviolet radiation, lipopolysaccharide and inhibitors of protein synthesis (Derijardet al., Cell1994,76,1025; Hanet al., Science1994,265,808; Raingeaudet al., J Biol. Chem.1995,270,7420; Shapiro and Dinarello,Proc. Natl. Acad. Sci. USA1995,92,12230).In contrast, ERK is activated by mitogens and growth factors (Bokemeyeret al., Kidney Int.1996,49,1187).

ERK2 is a widespread protein kinase, which reaches maximum activity when Thr183 and Tyr185 fosfauriliruyutza kinase MAR preceding events, MEK (Anderson et al.,Nature1990,343,651; Crewset al., Science1992, 255, 478).When activated ERK2 phosphorylates many regulatory proteins, including protein kinases Rsk90 (Bjorbaeket al., J. Biol. Chem.1995,270,18848) and MARKER (Rouseet al., Cell1994,78,1027),and transcription factors such as ATF2 (Raingeaudet al., Mol Cell Biol.1996,16,1247),Elk-1 (Raingeaudet al., Mol. Cell Biol.1996,16,1247),c-Fos (Chenet al., Proc. Natl Acad. Sci. USA1993,90,10952),and with the ICC (Oliveret al., Proc. Soc. Exp. Biol. Med.1995,210,162). ERK2 is also a target in the subsequent event of the Ras/Raf-dependent pathways (Moodieet al., Science1993,260,1658) and can help to replace the signals from these potentially oncogenic proteins. Found that ERK2 plays a role in the negative control growth of cancer cells of the breast (Frey and Mulder,Cancer Res.1993,57,628), and described the overexpression of ERK2 in cancer of the breast man (Sivraman et al., J Clin. Invest.1997,99,1478).Activated ERK2 was also involved in proliferation endothelin-stimulated cells of smooth muscles of the Airways, which confirms the role of this kinase for the treatment of asthma (Whelchelet al., Am. J. Respir. Cell Mol. Biol.1997,16,589).

Glikogensintetazy kinase-3 (GSK-3) is a serine/trainingtraining consisting of αand β-isoforms, each of which are encoded by specific genes (Coghlanet al., Chemistry & Biology2000, 7, 793-803; and Kim and Kimmel,Curr. Opinion Genetics Dev.,200010,508 to 514).GSK-3 is involved in various diseases, including Alzheimer's disease, disorders of the Central nervous system, such as manic depressive disorder, and neurodegenerative disease, and cardiomyocyte hypertrophy [PCT Application Nos.: WO 99/65897 and WO 00/38675; and Haqet al., J. Cell Biol.2000,151,117-130].These diseases are associated with abnormal operation of some routes of transmission signals of cells in which GSK-3 plays a role. Found that GSK-3 phosphorylates and simulates the activity of a number of reguljatornyh proteins. These proteins include glikogensintetazy, which is limiting the speed of an enzyme necessary for glycogen synthesis, associated with the microtubule protein Tau, a transcription factor gene β-catenin, the factor of transcription initiation 1F2B, as well as ATP citrate lyase, axinom factor-1 heat energy to what about the shock, C-Jun, c-myc, c-myb, CREB, and SERVAα. These diverse protein targets involve GSK-3 in many aspects of cellular metabolism, proliferation, differentiation and development.

In mediated GSK-3 way, which is acceptable for treatment of type II diabetes induced by insulin signaling leads to cellular glucose uptake and glycogen synthesis. Along with this by GSK-3 is a negative regulator of insulin-induced signal. Usually the presence of insulin causes inhibition mediated by GSK-3 phosphorylation and deactivation glikogensintetazy. Inhibition of GSK-3 leads to increased glycogen synthesis and glucose uptake [Kleinet al., PNAS1996,93,8455-8459; Crosset al., Biochem. J.1994,303,21-26; Cohen,Biochem. Soc. Trans.1993,21,555-567; and Massillonet al., Biochem J.1994,299,123-128].However, the diabetic patient whose insulin response is weakened, glycogen synthesis and glucose uptake is not increased despite the presence of relatively high levels of insulin in the blood. This leads to abnormally high levels of blood glucose with a sharp and prolonged effects that can eventually lead to cardiovascular disease, kidney failure and blindness. In these patients, normal, induced insulin inhibition of GSK-3 has no place. Opvantage, in patients with type II diabetes GSK-3 sverkhekspressiya [see PCT application: WO 00/38675]. Therapeutic inhibition of GSK-3, therefore, are potentially applicable for the treatment of diabetic patients suffering from impaired response to insulin.

The activity of GSK-3 is also associated with Alzheimer's disease. This disease is characterized by a well-known β-amyloid peptide and the formation of intracellular neurofibrillary tangles. Peptides Andβ formed from the amyloid protein precursor (APP) by the sequential proteolysis catalyzed by aspirinplease VASE, with subsequent cleavage presenilin-dependent γ-secretases. It was shown that antibodies against β-amyloid plaques can slowly reduce cognitive ability in patients with Alzheimer's disease (Hocket al., Neuron,2003,38,547-554) and, thus, other reducing β-amyloid strategies (for example, the development of agents capable of inhibiting β-amyloid peptide) may be applicable in the treatment of Alzheimer's disease and other psychotic and neurodegenerative disorders. In addition, neurofibrillary tangles contain hyperphosphorilated protein Tau, which fosfauriliruetsa on anomalous sites, and these agents are capable of inhibiting hyperphosphorylated protein Tau, can be applied to cured and Alzheimer's disease and other psychotic and neurodegenerative disorders.

It is known that GSK-3 phosphorylates these anomalous sites in cells in animal models. In addition, we discovered that inhibition of GSK-3 prevents hyperphosphorylated Tau in cells [Lovestoneet al., Current Biology1994,4,1077-86; and Brownleeset al., Neuroreport1997,8,3251-55]. Therefore, the activity of GSK-3 stimulates the generation of neurofibrillary tangles and the development of Alzheimer's disease. Also found that GSK-3 facilitates the processing of APP and the inhibitor of GSK-3 (lithium) inhibits the generation of Aβ-peptides by inhibiting GSK-3 (Phielet al. Nature2003,423,435-439). Thus, the development of inhibitors of GSK-3 can be applied to reduce the formation of amyloid plaques and neurofibrillary tangles, the pathological hallmark symptoms of Alzheimer's disease, and may be applicable to other treatment of psychotic and neurodegenerative disorders.

Another substrate of GSK-3 is β-catenin, which degraded after phosphorylation of GSK-3. Decreased levels β-catenin was detected in schizophrenic patients and were associated with other diseases related to increased death of neural cells [Zhonget al., Nature1998,395,698-702; Takashimaet al., PNAS1993,90,7789-93; and Peiet al., J. Neuropathol. Exp1997,56,70-78].

The activity of GSK-3 is also associated with stroke [Wanget al., Brain Res2000,859,381-5; Sasakiet al., Neurol Res2001,23,58-92; Hashimotoet al., J. Biol. Chem2002,277,32985-32991].

Subfamily of AGC kinases phosphorylate their substrates at residue serine and threonine and participates in various well-known processes transmission signals, including, but not limited to the above, the signal transmission cyclic ATP, a reaction to insulin, protection apoptosis, signal transmission diacylglycerol and regulation of translation protein (Petersonet al., Curr. Biol.1999,9,R521).This subfamily includes the RCA RCO (p-Akt), PCK, PRK1, 2, p70S6Kand PDK.

Found that the ACT (also known as RKV or Rac-PK beta), serine/trainingtraining, sverkhekspressiya in several types of cancer and is a mediator of the functions of normal cells [(Khwaja, A.,Nature1999,401,33-34); (Yuan, Z.Q.,et al., Oncogene2000,19,2324-2330); (Namikawa, K.,et al., J Neurosci.2000,20,2875-2886)].The ACT contains domain N-terminal homology Plaksina (PH), kinase domain and C-terminal "tail" region. So far found three isoforms ACT-kinase person (ACT-1, -2 and -3) [(Cheng, J.Q.,Proc. Natl. Acad. Sci. USA1992,89,9267-9271); (Brodbeck, D.et al., J. Biol. Chem.1999,274,9133-9136)]. Domain PH binds 3-phosphoinositides, which synthesized phosphatidylinositol-3-kinase (PI3K) upon stimulation by growth factors, such as obtained from platelet growth factor (PDGF), nerve growth factor (NGF) and insulin-like growth factor (FG-1) [(Kulik et al., Mol Cell. Biol,1997,17,1595-1606,); (Hemmings, B.A.,Science,1997,275,628-630)].The lipid binding domain of PH stimulates translocation of the ACT on the plasma membranes and facilitates the phosphorylation of other PH-demenagerait by protein kinases, PDK1 at Thr308, Thr309 and Thr305 for isoforms ACT 1, 2 and 3, respectively. The second is still unknown kinase is required for the phosphorylation of Ser473, Ser474 or Ser472 in the C-terminal "tails" of the ACT-1, -2 and -3, respectively, to create a fully activated enzyme ACT.

After location on the membrane ACT mediates several functions in the cell, including the metabolic actions of insulin (Calera, M.R.et al., J. Biol. Chem.1998,273,7201-7204),induction of differentiation and/or proliferation, protein synthesis and the stress response (Alessi, D.R.et al., Curr. Opin. Genet. Dev.1998,8,55-62).

Manifestations regulations amended the ACT appear as if the damage, and disease, and the most important is the manifestation of his cancer. The first assessment INSTRUMENT was associated with ovarian carcinoma person, when it was found that the expression of the ACT amplificare in 15% of cases (Cheng, J.Q.et al., Proc. Natl. Acad. Sci. U.S.A.1992,89,9267-9271). It was also discovered that she sverkhekspressiya in 12% of cases of pancreatic cancer (Cheng, J. Q.et al., Proc. Natl. Acad. Sci. U.S.A.1996,93,3636-3641).It was shown that the ACT-2 over xpresroute in 12% of ovarian carcinomas and that the amplification of the ACT was particularly frequent in 50% of undifferentiated tumors, confirming that the INSTRUMENT can also be associated with aggressiveness of the tumor (Bellacosa,et al., Int. J. Cancer1995,64,280-285).

Found that the RCA (also known as camp-dependent protein kinase) regulates many vital functions, including energy metabolism, gene transcription, proliferation, differentiation, reproductive function, secretion, and neural activity, memory, contractility and motor function (Beebe, S.J.,Semin. Cancer Biol.1994,5, 285-294).PKA is a tetramer hooperman, which contains two catalytic subunits, associated with homodimeric regulatory subunit (which is valid for the inhibition of the catalytic subunits). Upon binding of camp (activating enzyme) catalytic subunits dissociate from the regulatory subunits with the formation of the active serine/trionychinae (McKnight, G.S.et al., Recent Prog. Horm. Res.1988,44,pp. 307).Today found three isoforms of the catalytic subunit (C-α,-β and-γ) (Beebe, S.J.et al., J. Biol. Chem.1992,267,25505-25512),With-α-subunit is the most extensively studied mainly due to its high expression in primary and metastatic melanomas (Becker, D.et al., Oncogene1990, J, 1133).To date, strategies to modulate the activity of C-α-subunit including the Ute use of antibodies, molecules that block the activity of PKA by "targeting" on regulatory dimers and expression of antisense oligonucleotides.

Ribosomal protein kinase RS6K-1 and -2 are also members of the AGC subfamily of protein kinases and catalyze the phosphorylation and subsequent activation of ribosomal protein S6, which participated in positive translational regulation of mRNAs encoding components of the equipment of protein synthesis. These mRNAs contain oligopyrimidine tract in their 5'-transcriptional start site called TOR, which, as it was discovered, is essential for their regulation at the translational level (Volarevic, S.et al., Prog. Nucleic Acid Res. Mol. Biol.2001,65,101-186).RS6K-dependent phosphorylation of S6 is stimulated in response to various hormones and growth factors mainly through the PI3K path (Coffer, P.J.et al., Biochem. Biophys. Res. Commun,1994198,780-786), which may be under the regulation of mTOR, as rapamycin acts by inhibition activity RS6Kand blocking proteinkinase, especially in the regulation according to the type of feedback broadcast these mRNAs encoding ribosomal proteins (Kuo, C.J.et al., Nature1992, 555, 70-73).

In vitro PDK1 catalyzes the phosphorylation Thr252 in the activation loop of the catalytic domain R, which is redispensing for activity R (Alessi, D.R.,Curr. Biol,1998,i> 8,69-81).The study of rapamycin and deletion of the gene dp70S6K from Drosophila and RS6Kof mice have established the Central role R as in cell growth and signaling of cell proliferation.

3-Phosphoinositide-dependent protein kinase-1 (PDK1) plays a key role in regulating the activity of several kinases belonging to the AGC subfamily of protein kinases (Alessi, D.et al., Biochem. Soc. Trans2001,29,1). These include isoforms of protein kinase B (RCO), also known as the ACT), ribosomal S6-kinase R (S6K) (Avruch, J.et al., Prog. Mol. Subcell. Biol.2001,26,115) and ribosomal S6-kinase P90 (Frödin, M.et al., EMBO J.2000,19,2924-2934).PDK1, mediating the transmission signal, is activated in response to insulin and growth factors and the addition of cells to the extracellular matrix (signal transmission integrin). Once activated, these enzymes mediate many other cellular events by phosphorylation of key regulatory proteins that play an important role in the regulation of processes such as survival, growth, cell proliferation and regulation of glucose [(Lawlor, M.A.et al., J. Cell Sci.2001,114,2903-2910), (Lawlor, M.A.et al., EMBO J.2002,21,3728-3738)]. PDK1 is a protein of 556 amino acids from the N-terminal catalytic domain and C-terminal homology domain of pleckstrin (PH), which activates its substrate phosphorylation of these kinases in their loop activate the (Belham, C.et al., Curr. Biol.1999, 9, R93-R96).Many cancer in humans, including prostate and NSCL, have enhanced the function of the transmission path signal PDK1 due to a number of specific genetic events such as mutations of PTEN and overexpression of some key regulatory proteins [(Graff, J.R.,Expert Opin. Ther. Targets2002,6,103-113), (Brognard, J.,et al., Cancer Res.2001,61,3986-3997)].Inhibition of PDK1 as a potential mechanism for cancer treatment was demonstrated by transferowania PTEN-negative cancer cell line person (U87MG) antimyeloma the oligonucleotides directed against PDK1. The resulting decrease in the levels of PDK1 protein leads to reduced cell proliferation and survival (Flynn, P.,et al., Curr. Biol.2000,10,1439-1442). Therefore, the design of inhibitors of the ATP binding site PDK1 provides among other treatments target for cancer chemotherapy.

Another range of genotypes of cancer cells refers to the manifestation of the following six significant alternations in cellular physiology: self-sufficiency in the supply of the signal growth, evasion of apoptosis, the intensity for filing inhibitory growth signals, limitless replicative potential, continuous angiogenesis and invasion of tissue, leading to metastasis (Hanahan, D. et al., Cell 2000, 100, 57-70). PDK1 is a critical mediator of the path signal PI3K to the th regulates multitude cellular functions, including growth, proliferation and survival. Therefore, inhibition of this pathway may affect four of the six specific conditions for the development of cancer. It is assumed that as such, the PDK1 inhibitor may have an effect on the growth of a very wide range of human cancers.

In particular, elevated levels of activity of the PI3K pathway directly related to the development of a number of human cancers, the development of resistant to aggressive state (acquired resistance to chemotherapy and poor prognosis. This increased activity was attributed to a number of key events, including reduced activity of negative regulators of the pathway, such as the phosphatase PTEN, activating mutations in positive regulators of the pathway, such as Ras, and overexpression of components of the path, such as RCO, and examples include the brain (glioma), breast, head and neck, kidney, lung, liver, melanoma, ovary, pancreas, prostate, sarcoma, thyroid [(Teng, D. H.et al., Cancer Res.,199757,5221-5225), (Brognard, J.et al., Cancer Res.,2001,61,3986-3997), (Cheng, J.Q.et al., Proc. Natl. Acad.Sci.1996,93,3636-3641),(Int. J. Cancer1995,64,280), (Graff, J.R.,Expert Opin. Ther. Targets2002,6,103-113),(Am. J. Pathol.2001,159,431)].

In addition, the reduced path through gene "knockout"gene "knockdown", dominant from catalinae research and inhibitors in the form of small molecules ways demonstrated the reversal of many cancer phenotypes in vitro (some studies also demonstrated a similar effect in vivo), such as blocking proliferation, reduced survival and senzibilizirani cancer cells to the effects of chemotherapy of various types in a number of cell lines, related to cancer of the following organs: pancreas [(Cheng, J.Q.et al., Proc. Natl. Acad. Sci.1996,93,3636-3641),(Neoplasia2001,3,278)],lung [(Brognard, J.et al., Cancer Res.2001,61,3986-3997),(Neoplasia2001,3,278)],ovarian [(Hayakawa, J.et al., Cancer Res.2000,60,5988-5994),(Neoplasia2001,3,278)],breast cancer (Mol.Cancer Ther.2002,1,707),rectum [(Neoplasia2001,3,278), (Arico, S.et al., J. Biol. Chem.2002,277,27613-27621)], neck (Neoplasia2001,3,278),prostate [(Endocrinology2001,142,4795), (Thakkar, H.et al. J. Biol. Chem.2001,276,38361-38369), (Chen, X.et al., Oncogene2001,20,6073-6083)] and brain (glioblastoma) [(Flynn, P.et al., Curr. Biol.2000,10,1439-1442)].

Accordingly there is a need to develop inhibitors of the subfamilies of protein kinases FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), protein kinases CDK, GSK, SRC, ROCK, and/or SYK, which are applicable in the treatment of various diseases or conditions associated with activation of the subfamily of protein kinases FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), CDK, GSK, SRC, ROCK, and/or SYK, especially committed to the inadequate treatments currently suitable for most of these diseases.

T is now detected, the compounds of this invention and their pharmaceutically acceptable compositions are useful as inhibitors subfamily of protein kinases FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), protein kinases CDK, GSK, SRC, ROCK, and/or SYK. In some embodiments, the implementation of these compounds are effective as inhibitors of protein kinases FLT-3, JAK-3, PDK-1 and/or SYK. These compounds have the General formula I:

or are their pharmaceutically acceptable salts, where R1, R2, R3, R4and R5have the meanings specified below.

These compounds and their pharmaceutical compositions are applicable for the treatment or prevention of various diseases, including, but not limited to the above, heart disease, diabetes, Alzheimer's disease, immunodeficiency disorders, inflammatory diseases, hypertension, allergic diseases, autoimmune diseases, destructive bone disorders such as osteoporosis, proliferative diseases, infectious diseases, immunologically mediated, and viral diseases. These compositions are also applicable in the methods of preventing cell death and hyperplasia and therefore can be used for the treatment or prevention of reperfusion/ishem and upon impact, heart attacks and hypoxia body. Compositions are also applicable in the ways of prevention of thrombin-induced platelet aggregation. The compositions are particularly applicable to the treatment of such disorders as chronic myelogenous leukemia (CML), acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), rheumatoid arthritis, asthma, osteoarthritis, ischemia, cancer (including but not limited to the above, ovarian cancer, breast cancer and endometrial cancer), liver disease, including hepatic ischemia, heart disease, such as myocardial infarction and congestive heart failure, pathogenic immune status, including activation of T cells, and neurodegenerative disorders.

1. A General description of the compounds of the invention:

The present invention relates to a compound of the formula I:

or its pharmaceutically acceptable salt,

where R1represents hydrogen or Y-R', where Y is an optionally substituted C1-6-alkylidenes a circuit in which up to two methylene units optionally and independently replaced by-O-, -S-, -NR-, -OCO-, -COO - or-CO;

each R independently represents hydrogen or optionally substituted C1-6aliphatic group, each R' is independently ol dstanley a hydrogen or optionally substituted group selected from C1-6aliphatic group, a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic system ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or R and R', two cases of R, or two instances of R' taken together with the atom(s)with which they are associated, with the formation of the optional substituted 3-12-membered saturated, partially unsaturated, or fully unsaturated monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R2represents a -(T)nAr1or -(T)nCy1where T represents optionally substituted C1-4alkylidenes a circuit in which one methylene link T optionally replaced by-NR-, -S-, -O-, -CS-, -CO2-, -OCO-, -CO-, -COCO-, -CONR-, -NRCO-, -NRCO2-, -SO2NR-, -NRSO2-, -CONRNR-, -NRCONR-, -OCONR-, -NRNR-, -NRSO2NR-, -SO-, -SO2-, -PO-, -PO2- or-POR-; n is 0 or 1; Ar1represents an optionally substituted aryl group selected from 5-6-membered monocyclic or 8-12 membered bicyclic ring having 0-5 heteroatoms independently you the security of nitrogen, oxygen or sulfur; and Cy1is an optionally substituted group selected from a 3-7-membered saturated or partially unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-12 membered saturated or partially unsaturated bicyclic system ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

or R1and R2taken together with the nitrogen atom, form an optionally substituted 5-8-membered monocyclic or 8-12 membered bicyclic saturated, partially unsaturated or fully unsaturated ring having 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;

where Ar1Cy1or any ring formed by R1and R2taken together, are, each independently, optionally substituted x independent groups Q-Rxwhere x is 0-5, Q is a bond or C1-6-alkylidenes a circuit in which up to two methylene units of Q optionally replaced by-NR-, -S-, -O-, -CS-, -CO2-, -OCO-, -CO-, -COCO-, -CONR-, -NRCO-, -NRCO2-, -SO2NR-, -NRSO2-, -CONRNR-, -NRCONR-, -OCONR-, -NRNR-, -NRSO2NR-, -SO-, -SO2-, -PO-, -PO2- or-POR-; and each Rxis independently R', halogen, NO2, CN, OR', SR', N(R')2, NR'r COR', NR'r CONR'2, N CO 2R', COR', CO2R', OCOR', CON(R')2, OCON(R')2, SOR', SO2R', SO2N(R')2, NR'r SO2R', NR'r SO2N(R')2, COCOR', or the PINES2COR';

R3linked to the nitrogen atom either in 1-or 2-position of the ring and represents a (L)mAr2or (L)mCy2where L represents an optionally substituted C1-4alkylidenes a circuit in which one methylene link L is optionally replaced by-NR-, -S-, -O-, -CS-, -CO2-, -OCO-, -CO-, -COCO-,-CONR-, -NRCO-, -NRCO2-, -SO2NR-, -NRSO2-, -CONRNR-, -NRCONR-, -OCONR-, -NRNR-, -NRSO2NR-, -SO-, -SO2-, -PO-, -PO2- or-POR-; m is 0 or 1; Ar2represents an optionally substituted aryl group selected from 5-6-membered monocyclic or 8-12 membered bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and Cy2is an optionally substituted group selected from a 3-7-membered saturated or partially unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-12 membered saturated or partially unsaturated bicyclic system ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; where Ar2and Cy2each independently optionally substituted groups Z-Rywhere y is 0-5, Z isone communication or 1-6-alkylidenes a circuit in which up to two methylene units of Z optionally replaced by-NR-, -S-, -O-, -CS-, -CO2-, -OCO-, -CO-, -COCO-, -CONR-, -NRCO-, -NRCO2-, -SO2NR-, -NRSO2-, -CONRNR-, -NRCONR-, -OCONR-, -NRNR-, -NRSO2NR-, -SO-, -SO2-, -PO-, -PO2- or-POR-; and each Ryis independently R', halogen, NO2, CN, OR', SR', N(R')2, NR'r COR', NR'r CONR'2, NR'r CO2R', COR', CO2R', OCOR', CON(R')2, OCON(R')2, SOR', SO2R', SO2N(R')2, NR'r SO2R', NR'r SO2N(R')2, COCOR', or the PINES2COR';

R4represents hydrogen or C1-6alkyl, provided that when R5represents hydrogen, then R4also represents hydrogen;

R5represents hydrogen or R3and R5taken together, form an optionally substituted group selected from a 5-7-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10-membered saturated, partially unsaturated, or fully unsaturated bicyclic system ring having 0-3 heteroatoms independently selected from nitrogen, oxygen or sulfur, and

where any ring formed by R3and R5taken together, is optionally substituted with up to five substituents, selected and from W-R wwhere W represents a bond or C1-6-alkylidenes a circuit in which up to two methylene units of W are not necessarily replaced by-NR-, -S-, -O-, -CS-, -CO2-, -OCO-, -CO-, -COCO, -CONR-, -NRCO-, -NRCO2-, -SO2NR-, -NRSO2-, -CONRNR-, -NRCONR-, -OCONR-, -NRNR-, -NRSO2NR-, -SO-, -SO2-, -PO-, -PO2- or-POR-; and each RWis independently R', halogen, NO2, CN, OR', SR', N(R')2, NR'r COR', NR'r CONR'2, NRCO2R', COR', CO2R', OCOR', CON(R')2, OCON(R')2, SOR', SO2R', SO2N(R')2, NR'r SO2R', NR'r SO2N(R')2, COCOR', or the PINES2COR'.

In some embodiments, implementation of the compounds of the formula I observed one or more or all of the following conditions:

a) when R3represents unsubstituted phenyl and R1represents hydrogen, then R2is not

i) unsubstituted phenyl;

ii) the unsubstituted pyridium;

iii) a benzyl, substituted o-OMe;

iv) -(C=S)NH(C=O)phenyl;

v); or

vi) -(C=S)NH-naphthyl, or -(C=O)naphthyl, or

b) when R3represents a substituted or unsubstituted phenyl, then R2is not phenyl substituted in paraprotein oxazole, thiazole, thiadiazole, oxadiazole, tetrazole, triazole, diazelam or pyrazole;

(C) when R3represents phenyl, pyridyl, pyrimidinium or C is clohessy and R 1represents hydrogen, then R2does not represent phenyl, simultaneously substituted by one OMe group in metaprogram and one group of oxazole in paraprotein;

d) when R3is a 4-Cl-phenyl or 3,4-di-Cl-phenyl, then R2is not a p-Cl-phenyl;

e) when R3represents an unsubstituted pyrimidinyl, then R2is not unsubstituted phenyl, p-OMe-substituted by phenyl, p-OEt-substituted phenyl or o-OMe-substituted phenyl, or, when R3is a 4-IU-pyrimidinyl or 4,6-dimethylpyrimidine, then R2is not unsubstituted phenyl;

f) excludes compounds of formula I:

g) when R2is a 3-pyridinyl and R1represents hydrogen, then R3is not trimethoxybenzoyl;

h) when R3represents optionally substituted phenyl and R1represents hydrogen, then R2may not be -(C=S)NH(C=O)phenyl, -(C=O)NH, -(C=S)NH or -(C=O)CH2(C=O)phenyl;

i) when R1represents hydrogen, R2represents unsubstituted benzyl, then R3can't be thiadiazole, substituted by an optionally substituted phenyl;

j) when R1represents hydrogen, R2represents p is Ridel and R 3represents pyridyl, then R2may not be substituted by one or more CF3, Me, OMe, Br or Cl;

k) when R1represents hydrogen, R2represents pyridyl, then R3is not unsubstituted pyridium, unsubstituted quinoline, unsubstituted phenyl or unsubstituted isoquinoline;

l) when R1represents hydrogen and R2represents an unsubstituted quinoline, then R3there can be unsubstituted pyridium or unsubstituted quinoline;

m) when R1represents hydrogen, R2represents unsubstituted isoquinoline or unsubstituted naphthyl, then R3is not unsubstituted pyridium;

n) are excluded the compounds of formula I, having the General structure:

,

in which R1,R2and R3have the meanings specified above, M and K represent O or H2provided that K and M are different, a and b are each-CH2-, -NH-, -N-alkyl, N-aralkyl, -NCORa, -NCONHRbor NCSNHRbwhere Rarepresents a lower alkyl or aralkyl and Rbrepresents alkyl with an unbranched or branched chain, aralkyl or aryl, which may be either unsubstituted or substituted by one or more alkyl and/or halogenating is advised deputies;

about) are excluded the compounds of formula I, having the General structure:

,

in which R1and R2have the meanings indicated above, and r and s are equal, each independently, 0, 1, 2, 3, or 4, provided that the sum of s and r is at least 1;

p) excluded any one or more or all of the compounds of formula I having the following structure:

where R2represents NH(CH)(Ph)C=O(Ph);

where R2represents unsubstituted phenyl or phenyl substituted OMe, Cl or Me;

,

where R2represents unsubstituted phenyl or phenyl substituted OMe, Cl, Me, OMe, or R2represents unsubstituted benzyl;

,

where R2represents an optionally substituted aralkyl and Rcand Rdrepresent, each independently, IU, hydrogen, CH2Cl or Cl;

where Rerepresents optionally substituted phenyl;

,

where R2represents phenyl, optionally substituted Me, OMe, Br or Cl; or

q) when R1before the hat is hydrogen and R 2represents phenyl or optionally substituted phenyl and m is 1, then L cannot be a-CO-, -PINES2or PINES=CH-.

In some other embodiments, implementation of the compounds of formula I, when R1represents hydrogen and R2represents phenyl or optionally substituted phenyl and m is 1, then L cannot be a-CO-, -CS-, -CONR-, -CSNR-, -SO2-, -SO2NR-, -COSO2or CSSO2-.

The compounds of this invention include compounds described in General above, and additionally described here is illustrated by the classes, subclasses and species. Will be used herein the following definitions, unless otherwise noted. For the purposes of this invention, the chemical elements are identified in accordance with the Periodic table of the elements, CAS version, Handbook of Chemistry and Physics, 75thEd. In addition, General principles of organic chemistry are described in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry, 5thEd., Ed.: Smith, M.B. and March, J., John Wiley & Sons, New York: 2001, the full content of which is hereby incorporated by reference.

As described herein, compounds of the invention can be optionally substituted by one or more substituents, such as illustrated in the above General or cited as examples of particular classes, subclasses and in the DAMI invention. Should be taken that the phrase "optionally substituted" is used interchangeably with the phrase "substituted or unsubstituted". In General, the term "substituted" regardless of, precedes him, the term "optionally" or not, refers to the replacement of hydrogen radicals in a given structure with the radical of a particular Deputy. Unless otherwise noted, optionally substituted group may have a Deputy at each substitutable position of the group, and when more than one position in any given structure may be substituted by more than one Deputy, selected from a particular group, the substituents may be the same or different in different positions. Combinations of substituents addressed by the present invention are preferably such that they led to the formation of a stable or chemically possible connections. The term "stable", as used here, refers to compounds, which essentially do not change when they are subjected to processing requirements, definitions, and preferably their separation, purification, and use for one or more purposes described here. In some embodiments, the implementation of a stable compound or chemically possible connection is a connection that essentially does not change when the temperature is 40°or lower in the absence of moisture or other chemically reactive conditions, for at least one week.

The term "aliphatic" or "aliphatic group", as used here, means a straight (i.e. unbranched) or branched, substituted or unsubstituted hydrocarbon chain that is completely saturated or which contains one or more unsaturated chains, or a monocyclic hydrocarbon or bicyclic hydrocarbon that is completely saturated or that contains one or more unsaturated chains, but which is not aromatic (also here to "carbocycle", "cycloaliphatic" or "cycloalkyl"), which has one attachment point to the rest of the molecule. Unless otherwise noted, aliphatic groups contain 1-20 aliphatic carbon atoms. In some embodiments, the implementation of the aliphatic groups contain 1-10 aliphatic carbon atoms. In other embodiments, implementation of the aliphatic groups contain 1-8 aliphatic carbon atoms. In other embodiments, implementation of the aliphatic groups contain 1-6 aliphatic carbon atoms and in other embodiments, implementation of the aliphatic groups contain 1-4 aliphatic carbon atoms. In some embodiments, the implementation of the term "cycloaliphatic" (or "carbocycle" or "cycloalkyl"refers to monocyclic3-C8 8-C12the hydrocarbon that is completely saturated or that contains one or more unsaturated chains, but which is not aromatic, and which has one attachment point to the rest of the molecule and in which any individual ring in the specified bicyclic ring system has 3-7 members. Suitable aliphatic groups include, but are not limited to, an unbranched or branched, substituted or unsubstituted alkyl, alkeline, alkyline groups and their combinations (hybrids), such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl.

The term "heteroaromatics"used herein means an aliphatic group in which one or two carbon atoms are independently replaced by one or more atoms of oxygen, sulfur, nitrogen or silicon. Heteroaromatics groups can be substituted or unsubstituted, branched or unbranched, cyclic or acyclic, and include "heterocycle", "heterocyclyl", "heterocyclizations" or "heterocyclic" group.

The term "heterocycle", "heterocyclyl", "heterocyclizations" or "heterocyclic group"used herein means non-aromatic monocyclic, bicyclic or tricyclic system of rings, in kataraktis or more members of the ring are independently selected heteroatoms. In some embodiments, the implementation of the "heterocycle", "heterocyclyl", "heterocyclizations" or "heterocyclic" group has from three to fourteen members, where one or more ring members are heteroatoms independently selected from oxygen, sulfur, nitrogen or phosphorus, and where each ring is 3-7-mi membered ring.

The term "heteroatom" means one or more atoms of oxygen, sulfur, nitrogen, phosphorus, or silicon (including, any oxidized form of nitrogen, sulfur, phosphorus or silicon, quaternion the form of any nitrogenous base or substitutable nitrogen atom of the heterocyclic ring, for example N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl) or NR+(as in N-substituted pyrrolidinyl)).

The term "unsaturated"as used here, means that the group has one or more unsaturated chains.

The term "alkoxy" or "thioalkyl", as used here, refers to an alkyl group as defined earlier, is attached to the main carbon chain through an oxygen atom ("alkoxy") or sulfur ("thioalkyl").

The term "halogenated", "halogenoalkanes and halogenoalkane" means alkyl, alkenyl or alkoxy depending on what the case may be, substituted with one or more halogen atoms. The term "halogen" means F, Cl, Br or I.

The term "aryl", IP is olshey separately or as part of a larger group, as in "aralkyl", "arakaki" or "aryloxyalkyl", refers to monocyclic, bicyclic and tricyclic systems of the rings, having only five to fourteen members of the rings, where at least one ring in the system is aromatic and where each ring in the system contains 3 to 7 members. The term "aryl" may be used interchangeably with the term "aryl ring". The term "aryl" refers to heteroaryl ring systems, as described here above.

The term "heteroaryl", used alone or as part of a larger group, as in "heteroalkyl" or "heteroaromatics", refers to monocyclic, bicyclic and tricyclic systems of the rings, having only five to fourteen members in the ring, where at least one ring in the system is aromatic, at least one ring in the system contains one or more heteroatoms, and where each ring in the system contains 3 to 7 members. The term "heteroaryl" may be used interchangeably with the term "heteroaromatic ring" or the term "heteroaromatic".

Aryl (including kalkilya, Alcoxy, aryloxyalkyl and the like) or heteroaryl (including heteroalkyl, heteroaromatics and the like) group may contain one or a few is to deputies and, thus, it may be "optionally substituted". Unless otherwise noted above and herein, suitable substituents on the unsaturated carbon atom aryl or heteroaryl groups are selected from halogen; -R°; -OR°; -SR°; phenyl (Ph), optionally substituted-R°; -O(Ph), optionally substituted-R°; -(CH2)1-2(Ph), optionally substituted-R°; -CH=CH(Ph), optionally substituted-R°; -NO2; -CN; -N(R°)2, -NR°C(O)R°; -NR°C(S)R°; -NR°C(O)N(R°)2; -NR°C(S)N(R°)2; -NR°CO2R°; -NR°NR°C(O)R°; -NR°NR°C(O)N(R°)2; -NR°NR°CO2R°; -C(O)C(O)Ro; -C(O)CH2C(O)R°; -CO2R°; -C(O)R°; -C(S)R°; -C(O)N(R°)2; -C(S)N(R°)2; -OC(O)N(R°)2; -OC(O)R°; -C(O)N(OR°R°; -C(NOR°R°; -S(O)2R°; -S(O)3R°; -SO2N R°)2; -S(O)R°; -NR°SO2N R°)2, -NR°SO2R°; -N(ORoRo, -C(=NH)-N(R°)2, -P(O)2R°; -PO(R°)2, -OPO(R°)2; -(CH2)0-2NHC(O)R°; phenyl (Ph), optionally substituted by R°; -O(Ph), optionally substituted by R°; -(CH2)1-2(Ph), optionally substituted by R°or-CH=CH(Ph), optionally substituted by R°where each independent R° selected from hydrogen, optionally zameshennoj 1-6aliphatic group, an unsaturated 5-6 membered heteroaryl or heterocyclic ring, phenyl, -O(Ph), or-CH2(Ph), or, notwithstanding the above values, two independent R° at the same Deputy or different substituents, taken together with the atom(s)to which each R° bound, form an optionally substituted 3-12-membered saturated, partially unsaturated, or fully unsaturated monocyclic or bicyclic ring having 0-4 heteroatoms selected from nitrogen, oxygen or sulfur.

Optional substituents on the aliphatic group of R° selected from NH2, NH(C1-4aliphatic group), N(C1-4aliphatic)2group, halogen, C1-4aliphatic group, HE, (C1-4aliphatic) groups, NO2CN, CO2N, CO2(C1-4aliphatic) groups, (Halogens1-4aliphatic), or halo(C1-4aliphatic) groups, where each of the above With1-4aliphatic groups R° is unsubstituted.

Aliphatic or heteroaromatics group or non-aromatic heterocyclic ring may contain one or more substituents and, thus, may be "optionally substituted". Unless otherwise noted above and herein, suitable substituents on a saturated carbon atom aliphatic who or heteroaromatics group or non-aromatic heterocyclic ring selected from substituents listed above for the unsaturated carbon atoms of aryl or heteroaryl group and additionally include the following substituents: =O, =S, =NNHR*, =NN(R*)2, =NNHC(O)R*, =NNHCO2(alkyl), =NNHSO2(alkyl), or =NR*, where each R* is independently selected from hydrogen or optionally substituted C1-6aliphatic group.

Unless otherwise noted above and herein, optional substituents on the nitrogen atom non-aromatic heterocyclic ring is usually selected from R+, -N(R+)2, -C(O)R+, -CO2R+, -C(O)C(O)R+, -C(O)CH2C(O)R+, -SO2R+, -SO2N(R+)2, -C(=S)N(R+1)2, -C(=NH)N(R+)2or-NR+SO2R+where R+represents hydrogen, optionally substituted C1-6aliphatic group, optionally substituted phenyl, optionally substituted-O(Ph), optionally substituted-CH2(Ph), optionally substituted -(CH2)1-2(Ph); optionally substituted-CH=CH(Ph) or an unsubstituted 5-6-membered heteroaryl or heterocyclic ring having from one to four heteroatoms independently selected from oxygen, nitrogen or sulfur, or, notwithstanding the above values of two independent groups of R+at the same Deputy or different substituents, taken together with the atom(s), which is each R +bound, form an optionally substituted 3-12-membered saturated, partially unsaturated, or fully unsaturated monocyclic or bicyclic ring having 0-4 heteroatoms selected from nitrogen, oxygen or sulfur.

Optional substituents on the aliphatic group or the phenyl ring of R+selected from-NH2, -NH(C1-4aliphatic), N(C1-4aliphatic)2groups, halogen, C1-4aliphatic group, -OH, -O(C1-4aliphatic) groups, -NO2, -CN, -CO2H, -CO2(C1-4aliphatic), -O(Halogens1-4aliphatic), or halo(C1-4aliphatic) groups, where each of the above With1-4aliphatic groups of R+is unsubstituted.

The term "Allenova chain" refers to an unbranched or branched carbon chain, which may be fully saturated or have one or more unsaturated chains and has two points of connection to the rest of the molecule.

As detailed above, in some embodiments, the implementation of two independent R° (or R+, R, R' or any other characters, similar to those specified herein) are taken together with the atom(s)to which they are attached, education optionally substituted 3-12-membered saturated, partially unsaturated or fully unsaturated, Monaci the symbolic or bicyclic ring, having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

Examples of rings that are formed when two independent R° (or R+, R, R' or any other characters, similar to those specified herein) are taken together with the atom(s)with which they are associated, include rings, but are not limited to the above: a) when two independent R° (or R+, R, R' or any other character, similarly referred to here) are associated with the same atom and are taken with that atom to form a ring, for example, N(R°)2where both R° taken together with the nitrogen atom to form piperidine-1-ilen, piperazine-1-ilen, or morpholine-4-ilen group; and b) two independent R° (or R+, R, R' or any other characters, similarly referred to here) are associated with different atoms and are taken together with these atoms forming a ring, for example, when the phenyl group is substituted by two OR°these two R° taken together with the oxygen atoms to which they are attached, with the formation of a condensed 6-membered oxygen-containing ring. It should be clear that a variety of other rings can be formed when two independent R° (or R+, R, R' or any other character, similar to those specified herein) are taken together with the atom(s)to which the WMD each symbol is attached, and examples of rings that are specified in detail above, are not intended to limit.

Have in mind that unless otherwise noted, the patterns shown here, include all isomeric (e.g., enantiomeric, diastereomeric and geometric (or conformational) forms of the structure; for example, R and S configurations for each asymmetric center, (Z)- (E)-isomers on double bond, and (Z)- and (S)-conformational isomers. Thus, individual stereochemical isomers as well as mixtures of enantiomeric, diastereomeric, and geometric (or conformational) isomers of the present compounds are within the scope of the invention. Unless otherwise noted, all tautomeric forms of the compounds of the invention are within the scope of the invention. In addition, unless otherwise noted, there is also aware that the structure shown here, include compounds that differ only in the presence of one or more enriched isotopes of atoms. For example, compounds having the above structure, except for the replacement of hydrogen by deuterium or tritium, or the replacement of carbon-carbon enriched13With or14With, are within the scope of the invention. Such compounds are applicable, for example, as analytical tools or probes in biological assays.

As the op is Sano in General above for compounds of formula I, in some embodiments, the implementation of R2represents a -(T)nAr1. In some embodiments, the implementation of Ar1selected from one of the following groups:

where the values of Q and Rxstated in General above and listed here in classes and subclasses, and x is 0-5.

In other embodiments, the implementation of Ar1represents phenyl (a), pyridyl (b) (preferably attached in the 2-, 3 - or 4-position as shown in b-i, b-ii and b-iii), pyrimidinyl (s) (preferably attached in the 2-, 4 - or 5-position, as shown in C-i, C-ii and C-iii)

In the following embodiments, the implementation of R1represents a hydrogen, Ar1represents phenyl (a) and the compounds have the formula I-A or I-A':

In other embodiments, implementation of R2is a (T)nCy1. In preferred embodiments, the implementation of Cy1selected from one of the following groups:

where any substitutable carbon atom or nitrogen optionally substituted QRxand where Q and Rxmatter, in General above and shown here in classes and subclasses, and x is 0-5.

In the following embodiments, the implementation of Cy1selected from one of the following is x groups:

In other embodiments, implementation of R1represents hydrogen, Cy1represents cyclohexyl (v), tetrahydrofuranyl (her) (preferably attached in the 2-position) or cyclopropyl (ff), and compounds have one of the following formulas I-B, I-C, I-D, I-B', I-C or I-D':

In some embodiments, the implementation of R1represents hydrogen, C1-4alkyl, -CH2OCOR', -CH2OCOCHRNRR', COOR', -COCHROCOR', COR', -CO(CH2)3Other', where R' represents a C1-6alkyl or arcidiacono. In the most preferred options for implementation of R1represents hydrogen.

Examples of the groups T, when they are present, include CH2and CH2CH2-. In some other embodiments, the implementation of n is 0 and T is missing.

As detailed above, Ar1or Cy1may be optionally substituted at one or more substitutable carbon atoms or nitrogen up to 5 groups QRx. In some embodiments, the realization of x is 0-3 and Ar1or Cy1each independently substituted by 0-3 groups QRx. In the following embodiments, the implementation of x is 0 and Ar1or Cy1is unsubstituted.

In some embodiments, the implementation group QRxrepresent, each independently, R', ha is oven, CN, NO2, -N(R')2, -CH2N(R')2, -OR', CH2OR', -SR', -CH2SR', -COOR', -NRCOR', -CON(R')2, -SO2N(R')2, -CONR(CH2)2N(R')2, -CONR(CH2)3N(R')2, -CONR(CH2)4N(R')2, -O(CH2)2OR', -O(CH2)3OR', -O(CH2)4OR', -O(CH2)2N(R')2, -O(CH2)3N(R')3or-O(CH2)4N(R')2. In other embodiments, the implementation group QRxrepresent, each independently, Cl, Br, F, CF3, Me, Et, CN, -COOH, -N(CH3)2, -N(Et)2, -N(iPr)2, -O(CH2)Och3, -CONH2, -COOCH3, -OH, -CH2HE, -NHCOCH3, -SO2NH2methylendioxy, Ethylenedioxy, -O(CH2)2N-morpholino, -O(CH2)3N-morpholino, -O(CH2)4N-morpholino, -O(CH2)2N-piperazinil, -O(CH2)3N-piperidinyl, -O(CH2)4N-piperidinyl, -NHCH(CH2OH)phenyl, -CONH(CH2)2N-morpholino, -CONH(CH2)2N-piperazinil, -CONH(CH2)3N-morpholino, -CONH(CH2)3N-piperazinil, -CONH(CH2)4N-morpholino, -CONH(CH2)4N-piperazinil, -SO2NH(CH2)2N-morpholino, -SO2NH(CH2)2N-piperazinil, -SO2NH(CH2)3N-morpholino, -SO2NH(CH2)3N-piperazinil, -SO2NH(CH2)4N-morpholino, -SO2NH(CH2)4N-p is pyrazinyl, where each of the above phenyl, morpholino, piperazinilnom or piperidinyl groups is optionally substituted or optionally substituted group selected from C1-4alkoxy, phenyl, phenyloxy, benzyl, piperidinyl, piperazinil, morpholino or benzyloxy. In some embodiments, the implementation of the nitrogen atom piperidinyloxy or piperazinilnom group optionally substituted-COR'. In some other embodiments, the implementation of the nitrogen atom piperidinyloxy or piperazinilnom group optionally substituted-PINES2CN or-PINES3. Examples of groups QRxalso include the groups shown below in table 1.

It should be clear that certain classes of compounds of General formula I are particularly interesting. In some embodiments, the implementation of the present invention offers a monocyclic derivatives of triazole, in which R4and R5are, each, hydrogen, these compounds have the General formula II or II':

where R1and R2have the values stated above in General and are listed here in classes and subclasses; R3is a (L)mAr2or (L)mCy2where L represents an optionally substituted C1-4alkylidenes a circuit in which one methylene link L optional Zam is NENO-NR-, -S-, -O-, -CS-, -CO2-, -OCO-, -CO-, -COCO-, -CONR-, -NRCO-, -NRCO2-, -SO2NR-, -NRSO2-, -CONRNR-, -NRCONR-, -OCONR-, -NRNR-, -NRSO2NR-, -SO-, -SO2-, -PO-, -PO2- or-POR-; m is 0 or 1; Ar2represents an optionally substituted aryl group selected from 5-6-membered monocyclic or 8-12 membered bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and Cy2is an optionally substituted group selected from a 3-7-membered saturated or partially unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-12 membered saturated or partially unsaturated bicyclic system ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; where Ar1and Cy2each independently optionally substituted by y group Z-Rywhere y is 0-5, Z is a bond or C1-6-alkylidenes a circuit in which up to two methylene units of Z optionally replaced by-NR-, -S-, -O-, -CS-, -CO2-, -OCO-, -CO-, -COCO-, -CONR-, -NRCO-, -NRCO2-, -SO2NR-, -NRSO2-, -CONRNR-, -NRCONR-, -OCONR-, -NRNR-, -NRSO2NR-, -SO-, -SO2-, -PO-, -PO2- or-POR-; and each Ryis independently R', halogen, NO2, CN, OR', SR', N(R')2, NR'r COR', NR'r CONR'2, NR'r CO2R', COR', CO2R', OCOR', CON(R')2 , OCON(R')2, SOR', SO2R', SO2N(R')2, NR'r SO2R', NR'r SO2(R')2, COCOR', or the PINES2COR';

each R independently represents hydrogen or optionally substituted C1-6aliphatic group, each R' independently represents hydrogen or optionally substituted group selected from C1-6aliphatic group, a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic system ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or R and R', R two or R' in two cases, taken together with the atom(s)with which they are associated, with the formation of the optional substituted 3-12-membered saturated, partially unsaturated, or fully unsaturated monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

In some embodiments, implementation of the compounds of formula II, described above, takes into account one or more or all of the following conditions:

a) when R3represents unsubstituted phenyl and R1is the Wallpaper hydrogen, then R2is not

i) unsubstituted phenyl;

ii) the unsubstituted pyridium;

iii) a benzyl, substituted o-OMe;

iv) -(C=S)NH(C=O)phenyl;

v)or

vi) -(C=S)NH-naphthyl, or -(C=O)NH, or

b) when R3represents a substituted or unsubstituted phenyl, then R2is not phenyl substituted in paraprotein oxazole, thiazole, thiadiazole, oxadiazole, tetrazole, triazole, diazelam or pyrrole;

(C) when R3represents phenyl, pyridyl, pyrimidinium or cyclohexyl and R1represents hydrogen, then R2does not represent phenyl, simultaneously substituted by one OMe group in metaprogram and one group of oxazole in paraprotein;

d) when R3is a 4-Cl-phenyl, or 3,4-Cl-phenyl, then R2is not a p-Cl-phenyl;

e) when R3represents an unsubstituted pyrimidinyl, then R2is not unsubstituted phenyl, p-OMe-substituted by phenyl, p-OEt-substituted phenyl or o-OMe-substituted phenyl, or when R3is a 4-IU-pyrimidinyl or 4,6-dimethylpyrimidine, then R2is not unsubstituted phenyl;

f) excludes compounds of formula I:

g) when R2is a 3-pyridinyl and R1before the hat is hydrogen, then R3is not trimethoxybenzoyl;

h) when R3represents optionally substituted phenyl and R1represents hydrogen, then R2may not be -(C=S)NH(C=O)phenyl, -(C=O)NH, -(C=S)NH or -(C=O)CH2(C=O)phenyl;

i) when R1represents hydrogen, R2represents unsubstituted benzyl, then R3can't be thiadiazole, substituted by an optionally substituted phenyl;

j) when R1represents hydrogen, R2represents pyridyl and R3represents pyridyl, then R2may not be substituted by one or more CF3, Me, OMe, Br or Cl;

k) when R1represents hydrogen, R2represents pyridyl, then R3is not unsubstituted pyridium, unsubstituted quinoline, unsubstituted phenyl or unsubstituted isoquinoline;

l) when R1represents hydrogen and R2represents an unsubstituted quinoline, then R3there can be unsubstituted pyridium or unsubstituted quinoline;

m) when R1represents hydrogen and R2represents unsubstituted isoquinoline or unsubstituted naphthyl, then R3is not unsubstituted pyridium; or

n) when R1represents hydrogen and R2is the battle phenyl or optionally substituted phenyl and m is 1, then L cannot be a-CO-, -PINES2or PINES=CH-.

In some other embodiments, implementation of the compounds of formula I, when R1represents hydrogen and R2represents phenyl or optionally substituted phenyl and m is 1, then L cannot be a-CO-, -CS-, -CONR-, -CSNR-, -SO2-, -SO2NR-, -COSO2or CSSO2-.

As described in General above, in some embodiments, the implementation of Ar1selected from any one of the formulas from a to u, pictured above (including some sub-groups b-i, c-i, b-ii, b-iii, c-ii or c-iii) and in some other embodiments, the implementation of Cy1selected from any one of formulae v to ff, pictured above. However, it should be clear that for compounds of formula II described above, some additional connections are of special interest. For example, some are given as examples of options for implementation of the above compounds of General formula II or II' has a specific interest compounds include those compounds in which R1represents a hydrogen, Ar1represents optionally substituted phenyl and R3represents -(L)mAr2or -(L)mCy2these compounds have the formula II-A-(i), (II-A-(ii), II-A-(i)' or II-A-(ii)':

In some the option exercise for connections described directly above, m and n are both equal to 0.

Some other are provided as examples of embodiments, R1represents hydrogen, Cy1is an optionally substituted cyclohexyl, tetrahydrofuranyl or cyclopropyl and R3represents -(L)mAr2or -(L)mCy2these compounds have the formula II-B(i), (II-B-(ii), II-C(i), (II-c(ii), II-D-(i), (II-D-(ii)', II-B-(i)', II-B-(ii)', II-C(i)', II-C(ii)', II-D-(i)' or II-D-(ii)'.

In some embodiments, the implementation for compounds described directly above, m and n are both equal to 0.

In some other embodiments, implementation of the compounds of the General formula II and subgroup II-A-(i), (II-B(i), (II-C(i), (II-D-(i), (II-A-(i)', II-B-(i)', II-C(i)', II-D-(i)', described immediately above, Ar2selected from one of the following groups:

where any substitutable carbon atom or nitrogen optionally substituted by ZRYwhere Z and RYhave the meanings described in General above and described here in classes and subclasses, and y is 0-5.

In more preferred embodiments, the implementation of Ar2selected from one of the following groups:

In some embodiments, implementing the tvline for compounds of formula II and subgroup II-A-(ii), II-B-(ii), II-C(ii), II-D-(ii), II-A-(ii)', II-B-(ii)', II-C(ii)', II-D-(ii)' R3represents -(L)mCy2and Cy2selected from one of the following groups:

where any substitutable carbon atom or nitrogen optionally substituted by ZRYwhere Z and RYhave the meanings described in General above and described here in classes and subclasses, and y is 0-5.

In the following embodiments, the implementation of Cy2selected from one of the following groups i-b, or viii-b:

In some embodiments, the implementation of m is 1 and L represents-O-, -NR -, or-CH2-. In other embodiments, the implementation of m is 0.

In some other embodiments, implementation of the compounds of the General formula II, R1and R2have the meanings described in General above, and defined in classes and subclasses here, m is 0 and Ar2represents optionally substituted phenyl, 2-pyridyl, 2-thiazolyl, 2-pyrimidinyl, 6-pyrimidinyl, 4-pyridyl, benzothiazolyl or 2-chinoline, these compounds have one of the structures II-E-(i), (II-E-(ii), II-F-(i), (II-F-(ii), II-G-(i), (II-G-(ii), II-G'-(i), II-G'-(ii), II-H-(i), (II-H-(ii), II-I-(i), (II-I-(ii), II-I'-(i), (II-I'-(ii), II-J-(i), (II-J-(ii), II-E-(i)', II-E-(ii)', II-F-(i)', II-F-(ii)', II-G-(i)', II-G-(ii)', II-G'-(i)', II-G'-(ii)', II-H-(i)', II-H-(ii)', II-I-(i)', II-I-(ii)', II-I'-(i)', II-I'-(ii)', II-J-(i)', II-J-(ii)':

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In the following preferred embodiments implement Cy2represents cyclohexyl, and the compounds have the formula II-K-(i), (II-K-(ii), II-K-(i)' or II-K-(ii)':

As described above, Ar2or Cy2may be optionally substituted at any substitutable carbon atom or nitrogen up to 5 substituents ZRy. In some preferred embodiments, the realization of y is 0-3, and therefore Ar2or Cy2each independently substituted by 0-3 substituents ZRy. In other preferred embodiments, the realization of y is 0 and Ar2or Cy2is unsubstituted.

In preferred embodiments, the implementation of each of the groups ZRYindependently represents R', halogen, CN, NO2N(R')2, -CH2N(R')2, -OR', -CH2OR', -SR', -CH2SR', -COOR', -NRCOR', -CON(R')2, -SO2N(R')2, -CONR(CH2)2N(R')2, -CONR(CH2)3N(R')2, -CONR(CH2)4N(R')2, -O(CH2)2OR', -O(CH2)3OR', -O(CH2)4OR', -O(CH2)2N(R')2, -O(CH2)3N(R')2or-O(CH2)4N(R')2. In other embodiments, the implementation of the group ZRYrepresent, each independently, Cl, Br, F, CF3, Me, Et, CN, -COOH, -N(CH3)2, -N(Et)2-N(iPr) 2, -O(CH2)2Och3, -CONH2, -COOCH3, -OH, -CH2HE, -NHCOCH3, -SO2NH2methylendioxy, Ethylenedioxy, -O(CH2)2N-morpholino, -O(CH2)3N-morpholino, -O(CH2)4N-morpholino, -O(CH2)2N-piperazinil, -O(CH2)3N-piperazinil, -O(CH2)4N-piperazinil, -NHCH(CH2OH)phenyl, -CONH(CH2)2N-morpholino, -CONH(CH2)2N-piperazinil, -CONH(CH2)3N-morpholino, -CONH(CH2)3N-piperazinil, -CONH(CH2)4N-morpholino, -CONH(CH2)4N-piperazinil, -SO2NH(CH2)2N-morpholino, -SO2NH(CH2)2N-piperazinil, -SO2NH(CH2)3N-morpholino, -SO2NH(CH2)3N-piperazinil, -SO2NH(CH2)4N-morpholino, -SO2NH(CH2)4N-piperazinil, where each of the above phenyl, morpholino, piperazinilnom and piperidinium groups is optionally substituted or optionally substituted group selected from C1-4alkoxy, phenyl, phenyloxy, benzyl, piperidinyl, piperazinil, morpholino or benzyloxy. In some embodiments, the implementation of the nitrogen atom piperidinyloxy or piperazinilnom group optionally substituted-COR'. In some other embodiments, the implementation of the nitrogen atom piperidinyloxy or piperazinilnom group optional is entrusted substituted-PINES 2CN or-PINES3. Examples of groups ZRYalso include the groups shown below in table 1.

It should be clear that some subclasses of the above compounds of formulas II, II-A-(i), (II-A-(ii), II-B-(i), (II-B-(ii), II-C(i), (II-C(ii), II-D-(i), (II-D-(ii), II-E-(i), (II-E-(ii), II-F-(i) II-F-(ii), II-G-(i), (II-G-(ii), II-G'-(i), II-G'-(ii), II-H-(i), (II-H-(ii), II-I-(i), (II-I-(ii), II-I'-(i), (II-I'-(ii), II-J-(i) II-J-(ii), II-K-(i), (II-K-(ii), II', II-A-(i)', II-A-(ii)' II-B-(i)' II-B-(ii)' II-C(i)' II-C(ii)' II-D-(i)', II-D-(ii)', II-E-(i)', II-E-(ii)', II-F-(i)', II-F-(ii)', II-G-(i)', II-G-(ii)', II-G'-(i)', II-G'-(ii)', II-H-(i)', II-H-(ii)', II-I-(i)', II-I-(ii)', II-I'-(i)', II-I'-(ii)', II-J-(i)', II-J-(ii)', II-K-(i)', II-K-(ii)' are of particular interest.

For example, in some preferred embodiments, the implementation of the compounds of formulas II-A-(i), (II-A-(ii), II-B-(i), (II-B-(ii), II-C(i), (II-C(ii), II-D-(i), (II-D-(ii), II-A-(i)', II-A-(ii)', II-B-(i)'II-B-(ii)', II-C(i)', II-C(ii)', II-D-(i)' or II-D-(ii)' Ar2represents phenyl, pyridyl, pyrimidinyl (more preferably 2 - go 6-pyrimidinyl), chinoline, thiazolyl or benzothiazolyl, each of which is optionally substituted by 0-3 groups ZRYand Cy2represents cyclohexyl, optionally substituted by 0-3 groups ZRY. In a more preferred options for implementation of the compounds described above, n is 0 or n is 1 and T represents CH2; m is 0, x is 0-3; y is 0-3, and in each case QRxor ZRYindependently represents R', halogen, CN, NO2N(R')2, -CH2N(R')22OR', -SR', -CH2SR', -COOR', -NRCOR', -CON(R')2, -SO2N(R')2, -CONR(CH2)2N(R')2, -CONR(CH2)3N(R')2, -CONR(CH2)4N(R')2, -O(CH2)2OR', -O(CH2)3OR', -O(CH2)4OR', -O(CH2)2N(R')2, -O(CH2)2N(R')3or-O(CH2)4N(R')2. In more preferred embodiments, the implementation group QRXor ZRYrepresent, each independently, Cl, Br, F, CF3, Me, Et, CN, -COOH, -N(CH3)2, -N(Et)2, -N(iPr)2, -O(CH2)Och3, -CONH2, -COOCH3, -OH, -CH2HE, -NHCOCH3, -SO2NH2methylendioxy, Ethylenedioxy, -O(CH2)2N-morpholino, -O(CH2)3N-morpholino, -O(CH2)4N-morpholino, -O(CH2)2N-piperazinil, -O(CH2)3N-piperazinil, -O(CH2)4N-piperazinil, -NHCH(CH2OH)phenyl, -CONH(CH2)2N-morpholino, -CONH(CH2)2N-piperazinil, -CONH(CH2)3N-morpholino, -CONH(CH2)3N-piperazinil, -CONH(CH2)4N-morpholino, -CONH(CH2)4N-piperazinil, -SO2NH(CH2)2N-morpholino, -SO2NH(CH2)2N-piperazinil, -SO2NH(CH2)3N-morpholino, -SO2NH(CH2)3N-piperazinil, -SO2NH(CH2)4N-morpholino, -SO2NH(CH2)4N-piperazinil, DG is each of the above phenyl, morpholino, piperazinilnom and piperidinyl groups is optionally substituted or optionally substituted group selected from C1-4alkoxy, phenyl, phenyloxy, benzyl, piperidinyl, piperazinil, morpholino or benzyloxy. In some embodiments, the implementation of the nitrogen atom piperidinyloxy or piperazinilnom group optionally substituted-COR'. In some other embodiments, the implementation of the nitrogen atom piperidinyloxy or piperazinilnom group optionally substituted-PINES2CN or-PINES3.

For compounds of formula II-E-(i), (II-E-(ii), II-F-(i), (II-F-(ii), II-G-(i), (II-G-(ii), II-G'-(i), II-G'-(ii), II-H-(i), (II-H-(ii), II-I-(i), (II-I-(ii)II-I'-(i), (II-I'-(ii), II-J-(i), (II-J-(ii), II-K-(i), (II-K-(ii), II-E-(i)', II-E-(ii)', II-F-(i)', II-F-(ii)', II-G-(i)', II-G-(ii)', II-G'-(i)', II-G'-(ii)', II-H-(i)', II-H-(ii)', II-I-(i)', II-I-(ii)', II-I'-(i)', II-I'-(ii)', II-J-(i)', II-J-(ii)', II-K-(i)' or II-K-(ii)' Ar1is an optionally substituted group selected from phenyl and Cy1selected from cyclohexyl, furanyl or cyclopropyl, optionally substituted by 0-3 groups QRX. In a more preferred options for implementation of the compounds described above, n is 0 or n is 1 and T represents CH2; x is 0-3, y is 0-3, and in each case QRXor ZRYrepresents independently R', halogen, CN, NO2, -N(R')2, -CH2N(R')2, -OR', -CH2OR', -SR', -CH2SR', -COOR', -NRCOR', -CON(R')2, -SO2N(R')2/sub> , -CONR(CH2)2N(R')2, -CONR(CH2)3N(R')2, -CONR(CH2)4N(R')2, -O(CH2)2OR', -O(CH2)3OR', -O(CH2)4OR', -O(CH2)2N(R')2, -O(CH2)3N(R')2or-O(CH2)4N(R')2. In more preferred embodiments, the implementation group QRXor ZRYrepresent, each independently, Cl, Br, F, CF3, Me, Et, CN, -COOH, N(CH3)2, -N(Et)2, -N(iPr)2, -O(CH2)2Och3, -CONH2, COOCH3, -OH, -CH2HE, -NHCOCH3, SO2NH2methylendioxy, Ethylenedioxy, -O(CH2)2N-morpholino, -O(CH2)3N-morpholino, -O(CH2)4N-morpholino, -O(CH2)2N-piperazinil, -O(CH2)3N-piperazinil, -O(CH2)4N-piperazinil, -NHCH(CH2OH)phenyl, -CONH(CH2)2N-morpholino, -CONH(CH2)2N-piperazinil, -CONH(CH2)3N-morpholino, -CONH(CH2)3N-piperazinil, -CONH(CH2)4N-morpholino, -CONH(CH2)4N-piperazinil, -SO2NH(CH2)2N-morpholino, -SO2NH(CH2)2N-piperazinil, -SO2NH(CH2)3N-morpholino, -SO2NH(CH2)3N-piperazinil, -SO2NH(CH2)4N-morpholino, -SO2NH(CH2)4N-piperazinil, where each of the above phenyl, morpholino, piperazinilnom piperidinyl groups is optionally substituted or optionally substituted group selected from C1-4alkoxy, phenyl, phenyloxy, benzyl, piperidinyl, piperazinil, morpholino or benzyloxy. In some embodiments, the implementation of the nitrogen atom piperidinyloxy or piperazinilnom group optionally substituted-COR'. In some other embodiments, the implementation of the nitrogen atom piperidinyloxy or piperazinilnom group optionally substituted-PINES2CN or-PINES3.

In the following embodiments, implementation of the proposed compounds having one of the formulas:

In some preferred embodiments, the implementation of the compounds of formulas III, IV, V, VI, VII, VIII, IX, X or XI of x is 0-3, y is 0-3, and in each case QRXor ZRYare independently R', halogen, CN, NO2, -N(R')2, -CH2N(R')2, -OR', -CH2OR', -SR', -CH2SR', -COOR', -NRCOR', -CON(R')2, -SO2N(R')2, -CONR(CH2)2N(R')2, -CONR(CH2)3N(R')2, -CONR(CH2)4N(R')2, -O(CH2)2OR', -O(CH2)3OR', -O(CH2)4OR', -O(CH2)2N(R')2, -O(CH2)3N(R')2or-O(CH2)4N(R')2. In more preferred embodiments, the implementation group QRXor ZRYrepresent, each independently, Cl, Br, F, CF3, Me, Et, CN, -COOH, N(CH3)2, -N(Et)2, -N(iPr)2, -O(CH2)2Och3, -CONH2, COOCH3, -OH, -CH2HE, -NHCOCH3, -SO2NH2methylendioxy, Ethylenedioxy, -O(CH2)2N-morpholino, -O(CH2)3N-morpholino, -O(CH2)4N-morpholino, -O(CH2)2N-piperazinil, -O(CH2)3N-piperazinil, -O(CH2)4N-piperazinil, -NHCH(CH2OH)phenyl, -CONH(CH2)2N-morpholino, -CONH(CH2)2N-piperazinil, -CONH(CH2)3N-morpholino, -CONH(CH2)3N-piperazinil, -CONH(CH2)4N-morpholino, -CONH(CH2)4N-piperazinil, -SO2NH(CH2)2N-morpholino, -SO2NH(CH2)2N-piperazinil, -SO2NH(CH2)3N-morpholino, -SO2NH(CH2)3N-piperazinil, -SO2NH(CH2)4N-morpholino, -SO2NH(CH2)4N-piperazinil, where each of the above phenyl, morpholino, piperazinilnom and piperidinyl groups is optionally substituted or optionally substituted group selected from C1-4alkoxy, phenyl, phenyloxy, benzyl, piperidinyl, piperazinil, morpholino or benzyloxy. In some embodiments, the implementation of the nitrogen atom piperidinyloxy or piperazinilnom group optionally substituted-COR'. In some other embodiments, the implementation of the nitrogen atom piperidinyloxy or piperazinilnom group optionally substituted-PINES2CN or-WITH THE H 3.

In the following embodiments, the implementation of the compounds of formulas III, VI, VIII, IX, X and XI (including subgroups) are preferred as inhibitors of PDK-1.

In the following embodiments, the implementation of the compounds of formulas VI and VII (including subgroups) are preferred as inhibitors JAC-3. In some preferred embodiments, the implementation of the formulas VI and VII, applicable as inhibitors JAC-3, are replaced by at least one group ZRywhere ZRYrepresents N(R'), and compounds have the structure

In the following embodiments, the implementation of the compounds of formulas III, IV, VI and VII (including subgroups) are preferred as inhibitors of FLT-3.

Some other classes of compounds of the formula I, with a particular interest, include bi - or tricyclic derivatives of triazole, which

R1and R2have the meanings specified in the General above and described in classes and subclasses herein;

R4represents hydrogen or C1-4alkyl;

R3and R5taken together, form an optionally substituted group selected from a 5-7-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen or sulfur, and the 8-10-membered saturated, partially unsaturated, or fully unsaturated bicyclic system ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R3and R5taken together, form an optionally substituted group selected from a 5-7-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10-membered saturated, partially unsaturated, or fully unsaturated bicyclic system ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

where any ring formed by R3and R5taken together, optionally substituted with up to five substituents selected from W-RWwhere W represents a bond or C1-6-alkylidenes a circuit in which up to two methylene units of W are not necessarily and independently replaced by-NR-, -S-, -O-, -CS-, -CO2-, -OCO-, -CO-, -COCO-, -CONR-, -NRCO-, -NRCO2-, -SO2NR-, -NRSO2-, -CONRNR-, -NRCONR-, -OCONR-, -NRNR-, -NRSO2NR-, -SO-, -SO2-, -PO-, -PO2- or-POR-; and each Rwis independently R', halogen. NO2, CN, OR', SR', N(R')2, NR'r COR', NR'r CONR'2, NR'r CO2R', COR', CO2R', OCOR', CON(R')2, OCON(R')2, SOR', SO2R', SO2N(R')2, NR'r SO2R', NR'r SO2N(R')2, COCOR', or COCH2COR'./p>

In some embodiments, the communication described immediately above include one or more or all of the following constraints:

a) the compounds of formula I exclude compounds having the General structure:

in which R1, R2and R3have the above values, M and K represent O or H2provided that K and M are different, a and b are each-CH2-, -NH-, -N-alkyl-, -N-aralkyl-, -NCORa, -NCONHRbor NCSNHRbwhere Rarepresents a lower alkyl or aralkyl and Rbrepresents alkyl with an unbranched or branched chain, aralkyl or aryl, which may be either unsubstituted, or substituted by one or more alkyl and/or halogenoalkane deputies;

b) the compounds of formula I exclude compounds having the General structure:

in which R1and R2have the above meanings and r and s are equal, each independently, 0, 1, 2, 3, or 4, provided that the sum of s and r is at least 1;

C) the compounds of formula I exclude any one or more or all of the following connections:

,

in which R2represents NH(CH)(Ph)C=O(Ph);

,

in which R2represents unsubstituted phenyl or phenyl substituted OMe, Cl or Me;

,

in which R2represents unsubstituted phenyl or phenyl substituted OMe, Cl, Me, OMe, or R2represents unsubstituted benzyl;

,

in which R2represents an optionally substituted aralkyl and Rcand Rdrepresent, each independently, IU, hydrogen, CH2Cl or Cl;

in which Rerepresents optionally substituted phenyl;

,

in which R2represents phenyl, optionally substituted Me, OMe, Br or Cl, or

In some preferred embodiments, the communication have one of the following formulas:

where W and RWhave the meanings specified in the General above and described here in classes and subclasses, and R is 0-5.

As described in General above, in some preferred embodiments, the implementation of Ar1selected from any one of the formulas from a to u above (including some sub-groups b-i, c-i, b-ii, b-iii, c-ii or c-iii) and in some other embodiments, the implementation of Cy 1selected from any one of formulae v to ff, above. It should be clear, however, that for compounds described directly above, some additional compounds are compounds of special interest. For example, some are given as examples of options exercise of special interest are those compounds in which R1represents hydrogen and Ar1represents optionally substituted phenyl.

It should be clear that for compounds described above, some additional compounds are of particular interest. For example, some other are provided as examples of embodiments of particular interest are those compounds in which R1represents hydrogen and Ar1represents optionally substituted pyridyl.

It should be clear that for compounds described above, some additional connections are of special interest. For example, some other are provided as examples of embodiments, the implementation of special interest are those compounds in which R1represents voderady Ar 1is an optionally substituted cyclohexyl.

It should be clear that for compounds described above, some additional connections are of special interest. For example, in other cited as examples of options exercise of compounds of special interest includes those compounds in which R1represents hydrogen and Ar1represents an optionally substituted tetrahydrofuryl.

It should be clear that for compounds described above, some additional connections are of special interest. For example, in other cited as examples of options exercise of compounds of special interest includes those compounds in which R1represents hydrogen and Ar1represents an optionally substituted cyclopropyl.

As described above, any ring formed by R3and R5taken together, may be optionally substituted by up to 5 groups WRW. In some preferred embodiments, the implementation of p is 0-3. In other preferred embodiments, the implementation of p is 0 and the ring formed by R3and R 5is unsubstituted.

In preferred embodiments, the implementation group WRWrepresent, each independently R', halogen, CN, NO2N(R')2, -CH2N(R')2, -OR', -CH2OR', -SR', -CH2SR', -COOR', -NRCOR', -CON(R')2, -SO2N(R')2, -CONR(CH2)2N(R')2, -CONR(CH2)3N(R')2, -CONR(CH2)4N(R')2, -O(CH2)2OR', -O(CH2)3OR', -O(CH2)4OR', -O(CH2)2N(R')2, -O(CH2)3N(R')2or-O(CH2)4N(R')2. In other embodiments, the implementation group WRWrepresent, each independently, Cl, Br, F, CF3, Me, Et, CN, -COOH, N(CH3)2, -N(Et)2, -N(iPr)2, -O(CH2)Och3, -CONH2, COOCH3, -OH, -CH2HE, -NHCOCH3, -SO2NH2methylendioxy, Ethylenedioxy, -O(CH2)2N-morpholino, -O(CH2)3N-morpholino, -O(CH2)4N-morpholino, -O(CH2)2N-piperazinil, -O(CH2)3N-piperazinil, -O(CH2)4N-piperazinil, -NHCH(CH2OH)phenyl, -CONH(CH2)2N-morpholino, -CONH(CH2)2N-piperazinil, -CONH(CH2)3N-morpholino, -CONH(CH2)3N-piperazinil, -CONH(CH2)4N-morpholino, -CONH(CH2)4N-piperazinil, -SO2NH(CH2)2N-morpholino, -SO2NH(CH2)2N-piperazinil, -SO2 2)3N-morpholino, -SO2NH(CH2)3N-piperazinil, -SO2NH(CH2)4N-morpholino, -SO2NH(CH2)4N-piperazinil, where each of the above phenyl, morpholino, piperazinilnom and piperidinyl groups is optionally substituted or optionally substituted group selected from C1-4alkoxy, phenyl, phenyloxy, benzyl, piperidinyl, piperazinil, morpholino or benzyloxy. In some embodiments, the implementation of the nitrogen atom piperidinyloxy or piperazinilnom group optionally substituted-COR'. In some other embodiments, the implementation of the nitrogen atom piperidinyloxy or piperazinilnom group optionally substituted-PINES2CN or-PINES3. Examples of groups ZRWalso include the groups shown below in table 1.

In a more preferred options for implementation of the compounds described above, n is 0 or n is 1 and T represents CH2; p=0-3, y is 0-3; and in each case WRWor ZRYis independently R', halogen, CN, NO2, -N(R')2, -CH2N(R')2, -OR', CH2OR', -SR', -CH2SR', -COOR', -NRCOR', -CON(R')2, -SO2N(R')2, -CONR(CH2)2N(R')2, -CONR(CH2)3N(R')2, -CONR(CH2)4N(R')2, -O(CH2)2OR', -O(CH2)3OR', -O(CH2)4OR', -O(CH2)2(R') 2, -O(CH2)3N(R')2or-O(CH2)4N(R')2.

In more preferred embodiments, the implementation group WRWor ZRYrepresent, each independently, Cl, Br, F, CF3, Me, Et, CN, -COOH, N(CH3)2, -N(Et)2, -N(iPr)2, -O(CH2)2Och3, -CONH2, COOCH3, -OH, -CH2HE, -NHCOCH3, -SO2NH2methylendioxy, Ethylenedioxy, -O(CH2)2N-morpholino, -O(CH2)3N-morpholino, -O(CH2)4N-morpholino, -O(CH2)2N-piperazinil, -O(CH2)3N-piperazinil, -O(CH2)4N-piperazinil, -NHCH(CH2OH)phenyl, -CONH(CH2)2N-morpholino, -CONH(CH2)2N-piperazinil, -CONH(CH2)3N-morpholino, -CONH(CH2)3N-piperazinil, -CONH(CH2)4N-morpholino, -CONH(CH2)4N-piperazinil, -SO2NH(CH2)2N-morpholino, -SO2NH(CH2)2N-piperazinil, -SO2NH(CH2)3N-morpholino, -SO2NH(CH2)3N-piperazinil, -SO2NH(CH2)4N-morpholino, -SO2NH(CH2)4N-piperazinil, where each of the above phenyl, morpholino, piperazinilnom and piperidinyl groups is optionally substituted, or an optionally substituted group selected from C1-4alkoxy, phenyl, phenyloxy, benzyl, piperidinyl, piperaz the Nile, morpholino or benzyloxy. In some embodiments, the implementation of the nitrogen atom piperidinyloxy or piperazinilnom group optionally substituted-COR'. In some other embodiments, the implementation of the nitrogen atom piperidinyloxy or piperazinilnom group optionally substituted-PINES2CN or-PINES3.

In other preferred embodiments, the implementation of R4represents hydrogen or C1-4alkyl. In more preferred embodiments, the implementation of R4represents hydrogen or methyl. In the most preferred options for implementation of R4represents hydrogen.

Representative examples of compounds of formula I are summarized in table 1.

Table 1. Examples of compounds of the formula I:

III. General synthetic methodology:

The compounds of this invention can be obtained in General by methods known to experts in the field for similar compounds, as shown in the following General scheme and the following examples.

Scheme 1:

(I)=isopropanol at 100 degrees Celsius for 1 hour.

(II)=isopropanol at 100 degrees Celsius during the night.

The above scheme I shows the General method of obtaining connection the settings of the formula I. For example, the compounds of the invention can be obtained by the interaction of the source material (Q) with the appropriate amine with the formation of the intermediate compound (A). The subsequent interaction (A) with a suitable hydrazine get the described compounds of formula I.

The following scheme 2 shows the synthesis of some are given as examples of compounds in which R3represents -(L)mAr2these compounds also receive General procedures described above.

Scheme 2:

(I)=isopropanol at 100 degrees Celsius for 1 hour.

(II)=isopropanol at 100 degrees Celsius during the night.

In schemes 3, 4 and 5 shows the synthesis of some are given as examples of compounds in which R3and R5taken together, form an optionally substituted ring, as is indicated here. Although the following is a synthesis of some compounds, it should be clear that other bi - and tricyclic compounds, defined here in General, can also be obtained here described method.

Scheme 3:

In schemes 4 and 5 shows a General synthesis of compounds having the General formula:

Scheme 4:

Figure 5:

Although some are provided as examples of embodiments of the depicted and described above and herein, it should be clear that the compounds of the invention can be obtained according to the methods described in General terms above, using appropriate starting materials.

Pharmaceutically acceptable compositions

As described above, the present invention provides compounds that are inhibitors of protein kinases, and therefore these compounds are suitable for treating diseases, disorders and conditions, including, but not limited to the above, a heart breach, neurodegenerative violation, psychotic disorders, autoimmune disorder, a condition associated with organ transplantation, inflammatory violation, immunologically mediated violation, viral disease, or a bone disorder. In preferred embodiments, the implementation of the compounds are useful for the treatment of allergies, asthma, diabetes, Alzheimer's disease, Huntington's disease, Parkinson's disease, AIDS-associated dementia, amyotrophic lateral sclerosis (AML, disease, Lou Gehrig), multiple sclerosis (MS), schizophrenia, cardiomyocyte hypertrophy, reperfusion/ischemia (e.g. stroke), alopecia, cancer, hepatomegaly, cardiovascular disease, including cardiomegaly is, cystic fibrosis, viral disease, autoimmune diseases, atherosclerosis, restenosis, psoriasis, inflammation, hypertension, angina pectoris, cerebrovascular contraction, peripheral circulatory disorders, premature birth, atherosclerosis, vasospasm (cerebral vasospasm, coronary vasospasm), retinopathy, erectile dysfunction (ED), AIDS, osteoporosis, Crohn's disease and colitis, growth of Narita and disease Reno. In preferred embodiments, the implementation of a disease, condition or disorder is atherosclerosis, hypertension, erectile dysfunction (ED), reperfusion/ischemia (e.g. stroke) or vasospasm (cerebral vasospasm, coronary vasospasm).

Accordingly, in another aspect of the present invention proposed pharmaceutically acceptable compositions that contain any of the described compounds and optionally a pharmaceutically acceptable carrier, excipient or filler. In some embodiments, the implementation of these compositions optionally further comprise one or more additional therapeutic agents.

Must also be known that some of the compounds of the present invention may exist for treatment in free form or, if required, in the form of their pharmaceutically acceptable proizvodnju accordance with the present invention, pharmaceutically acceptable derivatives include, but not limited to, pharmaceutically acceptable prodrugs, salts, esters, salts of such esters, or any other adduct or derivative which upon administration to a patient in need this, capable of providing directly or indirectly the formation of compound otherwise described herein, or a metabolite or residue.

Used herein, the term "pharmaceutically acceptable salt" refers to those salts which are within the scope of sound medical judgment, are appropriate for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like and are commensurate with the acceptable benefit/risk. The term "pharmaceutically acceptable salt" means any non-toxic salt or salt of ester compounds of the present invention that when administered to a recipient is able to provide education either directly or indirectly, the compounds of this invention or its inhibition of the active metabolite or residue. Used herein, the term "its inhibitory active metabolite or residue" means that a metabolite or residue also is an inhibitor of the subfamilies of protein kinases FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), protein kinases CDK, GSK, SRC, RCK and/or SYK.

Pharmaceutically acceptable salts are well known in this field. For example, S.M Berge et al. described in detail pharmaceutically acceptable salt publishing Pharmaceutical Sciences, 1977, 66, 1-19, incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of this invention include salts derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid additive salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, Hydrobromic acid, phosphoric acid, sulfuric acid, Perlina acid, or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods known in this field, such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, bansilalpet, benzoate, bisulfate, borate, butyrate, comfort, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulphate, aconsultant, formate, fumarate, glucoheptonate, glycerol, gluconate, polysulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxyethanesulfonic, laktobion is t, lactate, laurate, lauryl, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toolswhat, undecanoate, valerate, and the like. Salts derived from appropriate bases include salts of alkaline metal, alkaline earth metal, ammonium and N+(C1-4alkyl)4. This invention also considers the quaternization of any basic nitrogen-containing groups of the compounds described herein. Soluble or dispersible in water or oil products can be obtained by such quaternization. Representative salts of alkaline or alkaline earth metals include sodium, lithium, potassium, calcium, magnesium and the like. These pharmaceutically acceptable salts include, if appropriate, nontoxic ammonium cations, Quaternary ammonium and amine formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkylsulfonate and arylsulfonate.

As described above, the pharmaceutically acceptable compositions of the present invention optionally contain a pharmaceutically acceptable carrier, excipient or n is politely, which, when used here includes any and all solvents, diluents, or other liquid fillers, auxiliaries for dispersion or suspension, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, solid binders, lubricants and the like, which is suitable for the required specific dosage forms. In Remington''s Pharmaceutical Sciences, Sixteenth Edition, E. W. Martin (Mack Publishing Co., Easton, Pa., 1980) described the various media used in the manufacture of pharmaceutically acceptable compositions, and different ways of their receipt. Except that any common the carrier medium is incompatible with the compounds of the invention, e.g. by producing any undesirable biological effect or otherwise harmful interactions with any other component(s) of the pharmaceutically acceptable composition, it is assumed that its application is within the scope of this invention. Some examples of materials which can serve as pharmaceutically acceptable carriers include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, such as albumin human serum, buffer substances, still is as phosphates, glycine, sorbic acid or potassium sorbate, and mixtures incomplete glyceridic esters of saturated vegetable fatty acids, water, salts or electrolytes, such as Protamine sulfate, sodium phosphate, potassium phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, polyacrylates, waxes, block copolymers, polyethylene-polyoxypropylene, lanolin, sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethylcellulose and cellulose acetate, powdered tragakant; Malte; gelatin; talc, excipients such as cocoa butter and waxes suppositories; oils such as peanut oil, cottonseed oil; safflower oil; sesame oil; olive oil; corn oil and soybean oil; glycols, such as propylene glycol or polyethylene glycol; esters, such as etiloleat and tillaart; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; water without pyrogen; isotonic saline; ringer's solution; ethyl alcohol and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, and colouring agents, visualaids the e agents, agents for coatings, sweeteners, giving a taste of agents and flavouring agents, preservatives and antioxidants can also be present in the composition in accordance with the decision of the manufacturer.

The use of compounds and pharmaceutically acceptable compositions

In another aspect, a method of treating or reducing the severity of proliferative disorders, cardiac disorders, neurodegenerative disorders, psychotic disorders, autoimmune disorders, conditions associated with organ transplantation, inflammatory disorders, and immunologically mediated disorders, viral diseases and bone disorders introducing an effective amount of a compound or pharmaceutically acceptable composition containing a compound, which requires the subject. In some embodiments, implementation of the present invention an "effective amount" of a compound or pharmaceutically acceptable composition is that amount which is effective to treat or reduce the severity of proliferative disorders, cardiac disorders, neurodegenerative disorders, psychotic disorders, autoimmune disorders, conditions associated with organ transplantation, inflammatory disorders, and immunologically mediated disorders, viral diseases and bone disorders. With the unity and composition by the method of the present invention can be introduced using any amount and any route of administration, effective to treat or reduce the severity of proliferative disorders, cardiac disorders, neurodegenerative disorders, autoimmune disorders, conditions associated with organ transplantation, inflammatory disorders, and immunologically mediated disorders, viral diseases and bone disorders. The exact quantity required will vary from subject to subject, depending on the species, age and General condition of the subject, the severity of the infection, the particular agent, its mode of administration and the like. Compounds of the invention are preferably manufactured in a uniform dosage form for ease of administration and uniformity of dosage. The expression "uniform dosage form", as used here, refers to a physically discrete unit agent, suitable for being treated patient. It should be clear, however, that the total daily dose required to receive the compounds or compositions of the present invention, is solved by the regular physician within the scope of sound medical judgment. A certain level of effective dose for any particular patient or organism will depend on various factors, including being treated with the violation and the seriousness of the violation; the specific activity of the applied compounds; certain applied the composition; age, body weight, General health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific applicable connection; the duration of the treatment; drugs used in combination or in conjunction with certain applicable connection and like factors well known in the medical field. The term "patient"as used here, means an animal, preferably a mammal, most preferably a human.

Pharmaceutically acceptable compositions of this invention can be injected into humans and other animals orally, rectally, parenterale, by intracavitary, intrawaginalno, intraperitoneally, topically (e.g., in the form of powders, ointments or drops), transbukkalno, in the form of an oral or nasal spray, or the like, depending on the severity of the exposed treatment of infection. In some embodiments, the implementation of the compounds of the invention can be administered orally or parenterally at dosage from about 0.01 mg/kg to about 50 mg/kg and preferably from 1 mg/kg to about 25 mg/kg of body weight of the subject per day one or more times per day to obtain the desired therapeutic effect.

Liquid dosage forms for oral administration include, but are not limited to the PE chislennym, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in this field, such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethylcarbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyleneglycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters and sorbitan and mixtures thereof. Besides inert diluents, the oral compositions can also include ancillary tools, such as wetting agents, emulsifying and suspendresume agents, sweeteners, flavorings and fragrances.

Injectable preparations, for example sterile injectable aqueous or oily suspensions, can be made known in this region methods using suitable dispersing or wetting agents and dispersing agents. The sterile injectable preparation may also be a sterile injectable solution, suspension or emulsion in a nontoxic parenterally is acceptable diluent or solvent, for example in the form of a solution in 1,3-butanediol. As an acceptable fillers and solvents may be used water, ringer's solution, U.S.P. (USP) and isotonic sodium chloride solution. In addition, as a solvent or suspendida environment usually apply sterile liquid fat. For this purpose, you can apply any mixed fatty oils, including synthetic mono - and diglycerides. In addition, when receiving an injectable drug use fatty acids such as oleic acid.

Injectable compositions can be sterilized, for example, by filtration through a retaining bacteria filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use.

In order to prolong the effect of the compounds of the present invention, it is often desirable to slow the absorption of the compound from subcutaneous or intramuscular injection. This can be done by applying a liquid suspension of crystalline or amorphous material with poor water solubility. The absorption rate of the connection then depends upon its rate of dissolution which, in turn, depends on the crystal size and crystalline form. Alternative options the ante slow the absorption of parenteral introduced forms the connection is achieved by dissolving or suspendirovanie compounds in the oil filler. Injectable forms depot receive education microcapsule matrix connection biorazlagaemykh polymers, such as polylactide-polyglycolide. The rate of release of the connection can be adjusted depending on the relationship of the connection to the polymer and the applied nature of the particular polymer. Examples of other biorazlagaemykh polymers include poly(orthoevra) and poly(anhydrides). Injectables type depot also get the capture compounds in liposomes or microemulsions which are compatible with body tissues.

Compositions for rectal or vaginal injection are preferably suppositories which can be obtained by mixing the compounds of this invention with suitable non-irritating with excipients or carriers such as cocoa butter, polyethylene glycol or waxes for suppositories, which are solid at ambient temperature but become liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound.

Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms the active compound is mixed, with at least one inert, pharmaceutically acceptable uh what scipionum or carrier, such as sodium citrate or calcium phosphate, and/or a) fillers or fillers, such as starches, lactose, sucrose, glucose, mannitol and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and the Arabian gum, (C) humectants, such as glycerol, d) dezinfeciruyuhimi agents such as agar-agar, calcium carbonate, potato starch or tapioca starch, alginic acid, certain silicates and sodium carbonate, e) agents, retarding dissolution such as paraffin, f) dissolution accelerators, such as Quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricating agents such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills dosage form may also contain buffering agents.

Solid compositions of a similar type may also be employed as fillers in soft and hard gelatin capsules using such excipients as lactose or milk sugar, as well as glycols of high molecular weight and the like. Solid is e dosage forms of tablets, tablets, capsules, pills and granules can be obtained with coatings and shells, such as intersolubility coatings and other coatings well known in the field of manufacturing of pharmaceutical preparations. They may not necessarily contain agents which impart opacity, and can also be a composition that releases the active ingredient(s) only, or predominantly, in certain part of the intestinal tract, optionally, the slow way. Examples covering compositions that can be used include polymeric substances and waxes. Solid compositions of a similar type may also be employed as fillers in soft and hard gelatin capsules using such excipients as lactose or milk sugar, as well as glycols of high molecular weight and the like.

The active compounds can also be in microencapsulated form with one or more excipients as noted above. Solid dosage forms such as tablets, pills, capsules, pills and granules can be obtained with coatings and shells, such as intersolubility coverage, regulating the release coatings and other coatings well known in the field of manufacturing of pharmaceutical preparations. In such solid dosage forms the active compound may be the mixed at least one inert diluent such as sucrose, lactose or starch. Such dosage forms can also contain, as it happens in normal practice, additional substances other than inert diluents, such as lubricant for tableting and other AIDS for tableting, such as magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. They may not necessarily contain agents which impart opacity, and can also be a composition that releases the active ingredient(s) only, or predominantly, in certain part of the intestinal tract, optionally, the slow way. Examples covering compositions that can be used include polymeric substances and waxes.

Dosage forms for local or percutaneous introduction of the compounds of this invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, forms for inhalation or patches. The active ingredient is mixed under sterile conditions with a pharmaceutically acceptable carrier and, when required, with any needed preservatives or buffers. Ophthalmic medication, eye drops, ear drops are also considered as being in predlagajem of the present invention. In addition, the present invention considers the use of transdermal patches, which have the added advantage of providing controlled delivery of the compound into the body. Such dosage forms can be manufactured by dissolving or distribution of compounds in a suitable medium. You can also use amplifiers absorption to increase flow connections flowing through the skin. You can adjust the speed of any provision regulating the speed of the membrane, or the distribution of compounds in a polymer matrix or gel.

As described in General above, the compounds of the invention can be investigated as inhibitors of protein kinases. In one embodiment, compounds and compositions of the invention are inhibitors of one or more of the subfamilies of protein kinases FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), CDK, GSK, SRC, ROCK, and/or SYK, and thus, without regard to any particular theory, the compounds and compositions are particularly applicable for treating or reducing the severity of the disease, condition or violation, when a disease, condition or violation involved the activation of one or more subfamilies of protein kinases from FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), protein kinases CDK, GSK, SRC, ROCK, and/or SYK. When the activation treatment tip can what astom protein kinases FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), CDK, GSK, SRC, ROCK, and/or SYK occurs when a particular disease, condition or violation of this disease, condition or disorder may be referred to as "indirect subfamily of protein kinases FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), CDK, GSK, SRC, ROCK, and/or SYK disease or symptom. Accordingly, in another aspect of the present invention, a method of treating or reducing the severity of the diseases, conditions or disorders where, in this pathological condition activation takes place by subfamily of protein kinases FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), CDK, GSK, SRC, ROCK, and/or SYK. The potency of the compound used in this invention as an inhibitor of the subfamily of protein kinases FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), CDK, GSK, SRC, ROCK, and/or SYK, can be analyzed in vitro, in vivo or in cell lines. The in vitro tests include assays that determine either the phosphorylation activity or ATPase activity, activated by subfamily of protein kinases FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), CDK, GSK, SRC, ROCK, and/or SYK. Other in vitro quantify the ability of the inhibitor to contact the subfamily of protein kinases FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), CDK, GSK, SRC, ROCK, and/or SYK. The binding of the inhibitor can be measured by labeling with radioactive isotope of the inhibitor prior to binding, highlighting the complex inhibitor subfamily of protein kinases/FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), CDK, GSK, SRC, ROCK, and/or SYK and measuring the amount of bound radioactive label. In the alternative case, the binding of the inhibitor can be determined by conducting competition experiment where new inhibitors are incubated with the subfamily of protein kinases FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), CDK, GSK, SRC, ROCK, and/or SYK associated with known radioactive labels.

The term "inhibits the measured image"used herein means a measurable change in activity of the subfamily of protein kinases FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), CDK, GSK, SRC, ROCK, and/or SYK between the sample containing the specified composition and kinase FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), CDK, GSK, SRC, ROCK, and/or SYK, and an equivalent sample containing kinase FLT-3, FMS, c-KIT, DERIVED, JAK, subfamily of AGC protein kinases (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), CDK, GSK, SRC, ROCK, and/or SYK in the absence of a specified composition.

The term "FLT-3-mediated disease"as used here, means any disease or worsened the condition in which, as is known, the kinase SEM is istwa FLT-3 plays a role. Such conditions include, without limitation, geopoliticheskie disorders, particularly acute myelogenous leukemia (AML), acute promyelocytic leukemia (APL) and acute limfotsity leukemia (ALL).

In accordance with another embodiment the invention provides treating or reducing the severity of FMS-mediated disease or condition in a patient, containing the stage of introduction of the indicated patient a composition according to the present invention.

The term "FMS-mediated disease"as used here, means any disease or worsened the condition in which, as is known, the kinase family of FLT-3 plays a role. Such conditions include, without limitation, cancer (including but not limited to the above, ovarian cancer, endometrial, breast cancer), inflammatory disorders and hypertension.

In accordance with another embodiment the invention provides treating or reducing the severity of C-KIT-mediated disease or condition in a patient, containing the stage of introduction of the indicated patient a composition according to the present invention.

The term "C-KIT-mediated disease"as used here, means any disease or worsened the condition in which, as is known, the kinase family of c-KIT plays a role. Such conditions include, without limitation, AML, chronic myelogenous leukemia (CML), m is stories, anaplastic both lymphoma, ALL, tumor gastrointestinal stromal (GIST), T-cell lymphoma, adenomatosnuu carcinoma, angiosarcoma, endometrial carcinoma, small cell lung cancer, prostate cancer, ovarian cancer, carcinoma of the breast, thyroid carcinoma, malignant melanoma and carcinoma of the colon.

In accordance with another embodiment the invention provides a method of treating or reducing the severity of CDK-2-mediated disease or condition in a patient, containing the stage of introduction of the indicated patient a composition according to the present invention.

The term "CDK-2-mediated disease"as used here, means any disease or worsened the condition in which, as is known, the kinase family of CDK-2 plays a role. Accordingly, these compounds are applicable for the treatment of diseases or conditions that are known to influence the activity of CDK-2 kinase. Such diseases and conditions include cancer, Alzheimer's disease, restenosis, angiogenesis, glomerulonephritis, cytomegalovirus disease, HIV disease, herpes, psoriasis, atherosclerosis, alopecia and autoimmune diseases such as rheumatoid arthritis, viral infections, neurodegenerative diseases, diseases associated with thymocytes apoptosis or proliferative what arsenia, resulting from the deregulation of the cell cycle, particularly the progression from phase G1to phase S.

In accordance with another embodiment the invention provides a method of treating or reducing the severity of GSK-3-mediated disease or condition in a patient, containing the stage of introduction of the indicated patient a composition according to the present invention.

In accordance with another embodiment the invention provides a method of treating or reducing the severity of Src-mediated disease or condition in a patient, containing the stage of introduction of the indicated patient a composition according to the present invention.

The term "Src-mediated disease"as used here, means any disease or worsened the condition in which, as you know, plays the role of Src. Such conditions include, without limitation, cancers, such as colon cancer, breast cancer, liver and pancreatic cancer, autoimmune diseases such as transplant rejection, allergies, rheumatoid arthritis, leukemia, disease, consisting in the reconstruction of bone, such as osteoporosis, and viral diseases, such as infection with hepatitis C.

In accordance with another embodiment the invention provides a method of treating or reducing the severity of Syk-mediated disease or condition is Oia patient, containing the stage of introduction of the indicated patient a composition according to the present invention.

The term "Syk-mediated disease" or "Syk-mediated condition", used here, means any disease or other degraded state in which, as you know, plays the role of Syk. Such conditions include, without limitation, allergic disorders, especially asthma.

The term "JAK-mediated disease"as used here, means any disease or other degraded state in which, as you know, plays the role of JAK. Such conditions include, without limitation, immune reactions, such as allergic reactions or hypersensitivity reactions (type I, asthma, autoimmune diseases such as transplant rejection, homologous disease, rheumatoid arthritis, side lateral sclerosis and multiple sclerosis, neurodegenerative disorders, such as family lateral lateral sclerosis (FALS), as well as solid and hematological malignancy, such as leukemia and lymphoma.

The term "PDK1-mediated condition" or "disease"as used here, means any disease or other degraded state in which, as you know, plays the role of PDK1. The term "PDK1-mediated condition" or "disease" means those diseases or conditions that facilitate the treatment of the receiving inhibitor of PDK1. PDK1-mediated disease or condition includes, but is not limited to, proliferative disorders and cancer. Specified cancer is preferably selected from pancreatic cancer, prostate cancer or ovarian cancer.

The term "PKA-mediated condition" or "disease"as used here, means any disease or other degraded state in which, as you know, plays the role of PKA. The term "PKA-mediated condition" or "disease" means those diseases or conditions that facilitate treatment by an inhibitor of PKA. PKA-mediated disease or condition includes, but is not limited to, proliferative disorders and cancer.

The term "p70S6K-mediated condition" or "disease"as used here, means any disease or other degraded state in which, as you know, plays the role of p70S6K. The term "p70S6K-mediated condition" or "disease" means those diseases or conditions that facilitate the treatment of inhibitor of p70S6K. p70S6K-mediated disease or condition includes, but is not limited to, proliferative disorders such as cancer and tuberose sclerosis.

The term "GSK-3-mediated disease"as used here, means any disease or other degraded the second state, which, as you know, plays the role of GSK-3. Such diseases or conditions include, without limitation, autoimmune diseases, inflammatory diseases, metabolic, neurological and neurodegenerative diseases (such as Alzheimer's, Huntington's disease, Parkinson's disease and movement disorders of basal nuclei, horey, dystonia, Wilson disease, the disease Peak, degeneration of the frontal part (brain), progressive supranuclear palsy (PSP), a disease Breitfeld-Jakob, thaumatology and corticobasal degeneration (CBD)), psychotic disorders (e.g. schizophrenia, AIDS-associated dementia, depression, bipolar disorder, and anxiety), cardio disease, allergies, asthma, diabetes, amyotrophic lateral sclerosis (AML, disease, Lou Gehrig), multiple sclerosis (MS), cardiomyocyte hypertrophy, reperfusion/ischemia, stroke and alopecia.

The term "ROCK-mediated condition" or "disease"as used here, means any disease or other degraded state in which, as you know, plays the role of a ROCK. The term "ROCK-mediated condition" or "disease" means those diseases or conditions that facilitate the treatment with ROCK inhibitor. ROCK-mediated disease or condition includes, but is not limited to, is hypertensia, angina, cerebrovascular contraction, asthma, impaired peripheral circulation, premature birth, cancer, erectile dysfunction, atherosclerosis, spasm (cerebral vasospasm and coronary vasospasm), retinopathy (e.g., glaucoma), inflammatory disorders, immune disorders, AIDS, osteoporosis, myocardial hypertrophy, the damage induced by ischemia/reperfusion, and endothelial dysfunction.

In other embodiments implementing the invention relates to a method of enhancing glycogen synthesis and/or lowering the levels of blood glucose in a patient in need thereof, introducing the indicated patient a therapeutically effective amount of a composition containing the compound of formula I. This method is particularly applicable to diabetic patients.

In another embodiment, the invention relates to a method of inhibiting the production of hyperphosphorylated Tau-protein in a patient in need thereof, introducing the indicated patient a therapeutically effective amount of a composition containing the compound of formula I. This method is particularly applicable when you stop the development or slow the progress of Alzheimer's disease.

In another embodiment, the invention relates to a method of inhibiting the phosphorylation β-catenin in a patient needs is the existing, introducing the indicated patient a therapeutically effective amount of a composition containing the compound of formula I. This method is particularly applicable for the treatment of schizophrenia.

It should be clear that the compounds and pharmaceutically acceptable compositions of the present invention can be used in combination therapies, that is, the compounds and pharmaceutically acceptable compositions can be introduced simultaneously with one or more other desired therapeutics or medical procedures, before or after such therapies or procedures. In particular combinations of treatments (therapies or procedures), which is used in the Raman scheme such treatments should take into account compatibility of the desired therapeutics and/or procedures and the desired therapeutic effect to be achieved. It should be clear that the applied treatment can achieve the desired action for the same violation (for example, the compound of the invention can be introduced with another agent used to treat the same disorder), or they can lead to different actions (for example, suppressing any negative actions). Used herein, additional therapeutic agents that are normally administered to treat or prevent a specific disease or condition, are known for the AK "suitable for being treated with disease or condition".

For example, chemotherapeutic agents or other anti-proliferative agents may be combined with the compounds of the present invention to treat proliferative diseases and cancer. Examples of known chemotherapeutic agents include, but are not limited to, for example, other treatment or anticancer agents that may be used in combination with anticancer patentable agents of the present invention may also be applied surgery, radiotherapy (several examples are gamma-radiation, neutron beam radiotherapy, electron beam radiotherapy, proton therapy, brachytherapy, and systemic treatment with radioactive isotopes, not to mention other therapies), endocrine therapy, treatment with biological response modifiers (interferons, interleukins and factor tissue necrosis (TNF), not to mention others), hyperthermia and cryotherapy, treatment agents to mitigate negative actions (e.g., antiemetics means) and other approved chemotherapeutic drugs, including, but not limited to the above, alkylating drugs (meteoritemen, chlorambucil, cyclophosphamide, melphalan, ifosfamide), antimetabolites(methotrexate), purine antagonists and Piri is dinovia antagonists (6-mercaptopurine, 5-fluorouracil, cytarabin, gemcitabine), spindle poisons (vinblastine, vincristine, vinorelbine, paclitaxel), podophyllotoxins (etoposide, irinotecan, topotecan), antibiotics (doxorubicin, bleomycin, mitomycin), nitrosoanatabine (carmustin, lomustin), inorganic ions (cisplatin, carboplatin), enzymes (asparaginase), and hormones (tamoxifen, leuprolide, flutamide and megestrol), GleevecTM, adriamycin, dexamethasone, and cyclophosphamide. For a more detailed discussion of updated cancer therapies see http://www.nci.nih.gov/, list of FDA approved medicines for Oncology in . and The Merck Manual, the seventeenth ed. 1999, the full contents of which are incorporated so as a reference.

Other examples of agents that can be combined with the inhibitors of this invention include, without limitation, agents for the treatment of Alzheimer's disease, such as aricept®and excelon®; agents for the treatment of Parkinson's disease such as L-DOPA/carbidopa, entacapone, ropinirol, pramipexol, parlodel, pergolid, trihexyphenidyl and amantadine; agents for treating multiple sclerosis (MS)such as beta interferon (e.g., Avonex®and Rebif®), Copaxone®and mitoxantrone; agents for the treatment of asthma, such as albuterol and singulair®; agents for treating schizophrenia such as zyprexa, risperdal, seroquel, and haloperidol; anti-inflammatory agents such as corticosteroids, TNF blockers, IL-1 RA, azathioprine, cyclophosphamide and sulfasalazine; immunomodulatory and immunosuppressive agents such as cyclosporine, tacrolimus, rapamycin, microfest mofetil, interferons, corticosteroids, cyclophosphamide, azathioprine and sulfasalazine; neurotrophic factors such as acetylcholinesterase inhibitors, MAO inhibitors, interferons, anti-convulsants, blockers of ion channels, riluzole, and agents against Parkinson's disease; agents for treating cardiovascular disease such as beta-blockers, ACE inhibitors, diuretics, nitrates, calcium channel blockers, and statins; agents for treating liver disease such as corticosteroids, cholestryamine, interferons and antiviral agents; agents for treating blood disorders such as corticosteroids, antileukemia agents and growth factors; and agents for treating disorders of the type of immunodeficiency, such as gamma globulin.

The amount of additional therapeutic agent present in the compositions of this invention should be not more than the amount that is usually administered in a composition containing such a therapeutic agent as the only active agent. The number of additional terapevticheskaja currently proposed compositions will be in the range from approximately 50% to 100% of the amount, usually present in the composition containing the agent as the sole therapeutically active agent.

The compounds of this invention or their pharmaceutically acceptable compositions can also be included in compositions for coating implantable medical devices such as prostheses, artificial valves, vascular grafts, stents and catheters. In accordance with this present invention, in another aspect, includes a composition for coating an implantable device containing the compound of the present invention, as described in General above and described in classes and subclasses here, and a carrier suitable for coating implantable devices. In another aspect of the present invention includes an implantable device coated with a composition comprising a compound of the present invention, as described in General above and in classes and subclasses, and a carrier suitable for coating implantable devices.

Vascular stents, for example, used to overcome restenosis (re-narrowing of the blood vessels after injury). However, patients using stents or other implantable devices, face the risk of clotting and platelet activation. These side effects can be prevented or weakened prewar the tion coating device pharmaceutically acceptable composition, containing the kinase inhibitor. Suitable coatings and the General getting coated implantable devices are described in U.S. patents 6099562, 5886026 and 5304121. Coatings are typically biocompatible polymeric materials, such as polymer hydrogel, polymethylsiloxane, polycaprolactone, polyethylene glycol, polylactic acid, ethylene vinyl acetate and mixtures thereof. The coating can be optionally additionally coated with a suitable top layer of Versiliana, polysaccharides, polyethylene glycol, phospholipids or combinations thereof to impart to the composition characteristics of the controlled release.

Another aspect of the invention relates to a method for inhibiting the activity of the subfamily of protein kinases FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), CDK, GSK, SRC, ROCK, and/or SYK in a biological sample or in a patient's body, which contains the introduction to the patient, or contacting the specified biological sample with a compound of formula I or a composition comprising the specified connection. The term "biological sample", as used here, includes, without limitation, cell cultures or extracts, the biopsy material obtained from the body of a mammal or extracts; blood, saliva, urine, feces, semen, tears, or other body fluids or extracts.

The inhibition activity of the subfamily PR is tenkins FLT-3, FMS, c-KIT, DERIVED, JAK, AGC (e.g., PKA, PDK, p70S6K-1 and -2 and RKV), CDK, GSK, SRC, ROCK, and/or SYK in a biological sample is useful for a variety of purposes that are known to the person skilled in the art. Examples of such purposes include, but are not limited to, blood transfusion, organ transplantation, storage of biological samples and biological tests.

EXAMPLES

A) Synthesis of compounds of the invention

Compounds of General formula I obtained according to the General procedure is as follows (schemes 1 and 2).

Source material (Q) was dissolved in 2-propanol to achieve a 1 M solution and the solution was heated to 100 degrees Celsius. The hot mixture was then added to the amine and the mixture was stirred for 1 hour in a sealed tube. HPLC showed that the reaction was complete and the reaction mixture was concentrated to dryness. The sample is then purified on a system of normal phase Combiflex. The solvent system was a mixture of dichloromethane:methanol. Elution was started with 0% methanol mixture and increased the content of methanol up to a maximum of 10% depending on the connection properties.

Source material (A) was dissolved in 2-propanol to achieve a 1 M solution. To this solution was then added 1 equivalent (In). The reaction was carried out in a sealed tube at 100 degrees Celsius during the night. When hydrazine was its HCl salt, EXT is ulali 1 equivalent of triethylamine.

The reaction was carried out as follows. The reaction mixture was concentrated to dryness, performed LC-MS to determine the completeness of the reaction. The remaining product was dissolved in methanol and washed through a pre-conditioned SCX column. The product was then suirable solution of methanol/ammonia. Product elution was concentrated to dryness and then purified by preparative chromatography with reversed phase Gilson.

The following examples describe as examples of the synthesis of various starting materials and compounds of the invention. After each series of procedures is a list of some are given as examples of compounds obtained by the methods of the invention.

Example 1

4-(3-Itfeel)morpholine. To a solution of 1,3-diiodobenzene (of 5.05 g of 15.3 mmol) in isopropanol (16 ml) under nitrogen atmosphere add morpholine (1,33 g of 1.33 ml of 15.3 mmol), potassium phosphate (6.50 g, 30,6 mol), ethylene glycol (1.90 g, 1.70 ml of 30.6 mmol) and copper iodide (I) (146 mg, 0,765 mmol). The mixture is heated at 80°C for 15 h and then cooled to room temperature. Solids are removed by filtration and the solution concentrated. The residue is purified column chromatography on silica gel, elwira a mixture of EtOAc:hexane (from 5 to 25% EtOAc), while receiving 4-(3-itfeel)morpholine (1,81 g, 41%) as a colourless oil. MS (ES+): m/z=290,0;1H NMR (CDCl 3, 500 MHz): δ a 3.15 (t, 4H), 3,85 (t, 4H), 6.87 in (DD, 1H), of 6.96-7,00 (m, 1H), 7,20 (m, 1H), 7,22-7,25 (m, 1H).

Example 2

Tert-Butyl ether N-(3-morpholine-4-ylphenyl)hydrazinecarboxamide acid. To a solution of 4-(3-itfeel)of the research (1,81 g, 6.26 mmol) in DMF (6.5 ml) in nitrogen atmosphere add tert-BUTYLCARBAMATE (993 mg, 7,52 mmol), copper iodide (I) (59,5 mg, 0,313 mmol), 1,10-phenanthroline (113 mg, 0,626 mmol) and cesium carbonate (2.85 g, 8,77 mmol). The mixture is heated at 80°C for 18 h and then cooled to room temperature. Add water (100 ml) and the mixture extracted with ethyl acetate. The organic layer is dried over MgSO4concentrate. The residue is purified column chromatography on silica gel with elution with a mixture of EtOAc:hexane (25 to 50% EtOAc), while receiving tert-butyl ether N-(3-morpholine-4-ylphenyl)hydrazinecarboxamide acid (1,14 g, 62%) as a yellow oil. MS (ES+): m/z=294,2;1H NMR (DMSO-d6, 500 MHz): δ the 1.44 (s, N), 3,06 (t, 4H), to 3.73 (t, 4H), equal to 4.97 (s, 2H), 6,66 (DD, 1H), 6,91 (d, 1H), 7,01-7,05 (m, 1H), 7,09-7,14 (m, 1H).

Example 3

Salt with HCl (3-morpholine-4-ylphenyl)of hydrazine. To a solution of tert-butyl ether N-(3-morpholine-4-ylphenyl)hydrazinecarboxamide acid (468 mg, 1,60 mmol) in methanol (20 ml) add a solution of 4 N. HCl in dioxane (10 ml). The mixture is stirred at room temperature overnight, then concentrated, recip what I Sol with 3 HCl (3-morpholine-4-ylphenyl)hydrazine (484 mg, 100%) as a yellow solid.

MS (ES+): m/z=194,1;1H NMR (CD3OD, 500 MHz): δ 3,60-3,71 (m, 4H), 4,06-to 4.15 (m, 4H), 7,06 (d, 1H), 7,26-7,35 (m, 2H), 7,50-7,58 (m, 1H).

Example 4

(6-Chloropyridin-3-yl)morpholine-4-ylmethanol. For the 6-chloronicotinamide (0,540 g of 3.07 mmol) in dichloromethane (10 ml) is added morpholine (0,294 g, 1.1 equivalents) followed by the addition of triethylamine (940 μl, 2.2 equivalents). The reaction mixture was stirred over night at room temperature, thus obtaining (6-chloropyridin-3-yl)morpholine-4-ylmethanol. Mass spectrometry showed the presence of starting material, 6-chloronicotinamide and showed accurate ion M+. Conduct water treatment product and raw material is transferred to the next stage. The crude residue (6-chloropyridin-3-yl)morpholine-4-ylmethanol has a lot 0,610 g (yield 88%) after water treatment.

Similarly receive the following connections:

/tr>
NameMS (M+N)Retention time (HPLC method)1H NMR, 500 MHz (solvent)
(6-(Chloropyridin-3-yl)morpholine-4-ylmethanol226,993,15
(6-Chloropyridin-3-yl)-(4-methylpiperazin-1-yl)methanon239,951,0
6-Chloro-N-(2-dimethylaminoethyl)-nicotinamide227,971,26

Example 5

(6-Hydrazinopyridazine-3-yl)morpholine-4-ylmethanol. To (6-chloropyridin-3-yl)morpholine-4-ylmethanone (0,649 g of 2.86 mmol) in ethanol (6 ml) is added 0,270 μl (3.0 equivalents) of hydrazine followed by the addition 438,9 μl of triethylamine (1.1 equivalent). The reaction mixture was stirred over night at 100°thus (6-hydrazinopyridazine-3-yl)morpholine-4-ylmethanol. The reaction mixture is filtered and then concentrated to dryness. The crude residue (6-hydrazinopyridazine-3-yl)morpholine-4-ylmethanol has a lot 0,372 g (yield 76%).

Similarly receive the following connections:

NameMS (M+N)
(6-Hydrazinopyridazine-3-yl)morpholine-4-ylmethanol222,92
(6-Hydrazinopyridazine-3-yl)-(4-methylpiperazin-1-yl)methanon236,00
N-(2-Dimethylaminoethyl)-6-hydrazinonicotinamide224,01

Example 6

6-Hydrazinonicotinamide (CF#H-1). A mixture of 6-chloronicotinamide (2,77 g, 20 mmol) and hydrazine hydrate (15 ml) was stirred at 100°C for 3 h and evaporated. The residue is suspended in afire filter, then suspended in sodium bicarbonate solution and filtered, washing with water, and dried, thus obtaining 6-hydrazinonicotinamide (1.25 g, yield 46%) as a reddish brown solid.

1H NMR (DMSO-d6, 500 MHz): 8,59 (s, 1H), 8,35 (s, 1H), 7,74 (d, 1H), 6.75 in (s, 1H), of 4.44 (s, 2H) ppm; MS (FIA) 135,1 (M+H).

Similarly receive the following connections

Name1H NMR
Benzothiazole-2-ilkerin(DMSO-d6, 500 MHz): 8,58 (s, 1H), 7,79 (d, 2H), was 7.36 (t, 2H), 7,25 (m, 1H), 7,10 (s, 1H), a 4.86 (s, 2H) ppm
(6-Triptorelin-2-yl)hydrazine(DMSO-d6, 500 MHz): of 8.04 (s, 1H), 7,65 (t, 1H), 6,97 (d, 1H), 6,92 (d, 1H), 4,25 (2N)

Example 7

(2-Chloropyrimidine-4-yl)hydrazine. To a solution of 2,4-dichloropyrimidine (1,49 g, 10.0 mmol) in ethanol (25 ml), add triethylamine (2,02 g, 2,78 ml, 20.0 mol) and hydrazine (321 mg 0,321 ml, 10.0 mmol). The mixture is stirred at room temperature for 2 hours. Water is added and the mixture extracted with dichloromethane. The organic layer is dried over MgSO4concentrate. The residue is purified column chromatography on silica gel with elution with a mixture of methanol:dichloromethane (2 to 5% methanol)to give (2-chloropyrimidine-4-yl)hydrazine (330 mg, 23%) as a white solid. MS (ES+): m/z=144,9.

<> Example 8

Pyrimidine-4-ilkerin. To a solution of (2-chloropyrimidine-4-yl)hydrazine in methanol added ammonium formate and Pd/C (10%). The mixture is heated at 55°C for 15 hours. The mixture is cooled to room temperature and filtered and the filtrate concentrated. Water is added and the mixture extracted with dichloromethane. The organic layer is dried over MgSO4and concentrate, while receiving pyrimidine-4-ilkerin (62,0 mg, 25%) as a yellow solid.

MS (ES+): m/z=111,3;1H NMR (CD3OD, 500 MHz): (s, W, 1H), of 8.06 (d, 1H), 8,39 (s, 1H)..

Scheme 6

Example 9

(3-Phenoxyphenyl)hydrazine. To a solution of 3-phenoxypyridine (2,32 g, 12.5 mmol) in methanol (5 ml), water (10 ml) and concentrated HCl (3 ml) at 0°add in the form of quick drops of a solution of sodium nitrite (0.87 g, 12.7 mmol) in water (2 ml). The reaction mixture was stirred 10 min, then treated by addition in the form of quick drops at 0°With solution of chloride dihydrate tin (6,77 g, 30 mmol) in concentrated HCl (25 ml). The reaction mixture is stirred for 1 hour then set the pH to ˜7 using 6 N. NaOH and sodium bicarbonate, filtered through celite, washed with a mixture of 1:3 methanol:dichloromethane. The filtrate is separated, the aqueous phase of the extras is giraut a mixture of 1:3 methanol:dichloromethane (2x). The combined organic layer is dried over sodium sulfate, evaporated, then purified flash chromatography (SiO2) with elution with a mixture of 35:65 ethyl acetate:hexane, while receiving (3-phenoxyphenyl)hydrazine (1.78 g, 71%yield) as an orange oil.1H-NMR (CDCl3, 500 MHz) 7,30 (m, 2H), 7,14 (t, 1H), was 7.08 (t, 1H), 7,00 (m, 2H), of 6.52 (m, 1H), 6,47 (m, 1H), 6,45 (m, 1H), 5,2 (Shir. 1H), 3,5 (Shir. 2H) ppm; MS (FIA) 201,1 (M+H); HPLC (method A) 2,887 minutes

Similarly receive the following connection:

NameMS (M+N)HPLC, method a1H NMR
(2-fluoro-4-itfeel)hydrazine253,02,373(CDCl3, 500 MHz) 7,28 (d, 1H), 7,18 (DD, 1H), PC 6.82 (t, 1H), 5,38 (s, 2H), 3,49 (s, 2H) ppm

Scheme 7

Example 10

4-Chloro-2-piperidine-1-Yeremey and 2-chloro-4-piperidine-1-Yeremey

These intermediate compounds receive procedure K. Yoshida et al., J. Chem. Soc. Perkins Transactions I., (1992), 919-922. A solution of 2,4-dichloropyrimidine (4,00 g, 26.8 mmol) and 1-methylpiperidine (of 3.25 ml, 29.5 mmol) in 1,4-dioxane (60 ml) was stirred at 100aboutC for 3 h, then cooled and evaporated. Purification with flash chromatography (SiO2) with elution with a mixture of 15:85 ethyl acetate:hexane gives 4-chloro-2-piperidine-1-and the pyrimidine (0,58 g, yield 12%) as a pale yellow solid:1H-NMR (CDCl3, 500 MHz) of 8.06 (d, 1H), 6,37 (d, 1H), 3,70 (m, 4H), to 1.61 (m, 2H), 1,53 (m, 4H) ppm; MS (FIA) 198,1(M+H);HPLC (method A) 3,550 min and 2-chloro-4-piperidine-1-Yeremey (1,87 g, yield 38%) as white solids:1H-NMR (CDCl3, 500 MHz) 8,01 (d, 1H), 6,41 (d, 1H), the 3.65 (m, 4H), at 1.73 (m, 2H), of 1.65 (m, 4H) ppm; MS (FIA) 198 (M+H); HPLC (method A) 2,583 minutes

Similarly receive the following connection:

NameMS (M+N)HPLC, method a1H NMR
4-Chloro-2-(4-methylpiperazin-1-yl)pyrimidine213,22,326(DMSO-d6, 500 MHz) 8,30 (d, 1H), of 6.71 (d, 1H), 3,70 (m, 4H), to 2.35 (m, 4H), of 2.21 (s, 3H) ppm

Scheme 8

4-Chloro-6-(4-methylpiperazin-1-yl)pyrimidine

4,6-Dichloropyrimidine (2 g, a 13.4 mmol) and N-methylpiperazine (1.5 ml, of 13.4 mmol) was dissolved in 20 ml of THF together with tea (1.9 ml, of 13.4 mmol) and stirred for 18 hours. THF is evaporated and add 10 ml of water and the mixture is then extracted with DCM. The DCM layer is dried over sodium sulfate, filtered and evaporated, thus obtaining 2.4 g of 4-chloro-6-(4-methylpiperazin-1-yl)pyrimidine as a yellow waxy solid, which is used without further purification.

[6-(4-Meth is piperazin-1-yl)pyrimidine-4-yl]hydrazine

4-Chloro-6-(4-methylpiperazin-1-yl)pyrimidine (200 mg, of 0.94 mmol) and hydrazine hydrate (200 μl, 4 mmol) is heated to 180aboutC for 6 min in a personal chemical microwave oven. The solvent is evaporated, thus obtaining [6-(4-methylpiperazin-1-yl)pyrimidine-4-yl]hydrazine as a yellow-brown crystals, which is used without further purification.

Similarly receive the following connections:

6-Morpholine-4-Yeremey-4-yl)hydrazineMS ES+ 196,2
N'-(6-Hydrazinopyridazine-4-yl)-N,N-dimethylated-1,2-diamineMS ES+ 197,1
[1-(6-Hydrazinopyridazine-4-yl)pyrrolidin-3-yl]dimethylamineMS ES+ 223,2

Example 11

[6-(4-Ethylpiperazin-1-yl)pyrimidine-4-yl]hydrazine

4,6-Dichloropyrimidine (1.1 g, 7.4 mmol) was dissolved in 20 ml of isopropanol, add potassium carbonate (2 g, 15 mmol) and N-ethylpiperazine (843 mg, 7.4 mmol). The mixture is stirred at room temperature for 18 h, then add hydrazine (1.6 g, 50 mmol) and heated to boiling under reflux for 22 hours. The mixture is cooled and filtered, then the filtrate is evaporated solvent. The residue is dissolved in 20 ml of boiling acetonitrile and filtered. Upon cooling, a white precipitate is formed. The precipitate is filtered off, get compressedfile 1 g of [6-(4-ethylpiperazin-1-yl)pyrimidine-4-yl]hydrazine as a white solid (60%). MS ES+ 223,2.

Scheme 9

(4-piperidine-1-Yeremey-2-yl)hydrazine. Specified in the header of the get connection, as described in example 10.

1H-NMR (DMSO-d6, 500 MHz) of 7.82 (width, 1H), 7,74 (width, 1H), 5,88 (s, 1H), 4,17 (s, 2H), the 3.65 (m, 4H), 1,58 (m, 2H), 1,45 (m, 4H) ppm; MS (FIA) 194,2 (M+H);HPLC (method A) 0,648 minutes

Similarly receive the following connections:

NameMS (M+N)HPLC, method a1H NMR
(2-piperidine-1-Yeremey-4-yl)hydrazine194,22,213(DMSO-d6, 500 MHz) 7,79 (d, 1H), 7,42 (s, 1H), 6,04 (d, 1H), 3,98 (s, 2H), 3,54 (m, 4H), to 1.61 (m, 2H), 1,48 (m, 4H) ppm
-Methylpiperazin-1-yl)-Yeremey-4-yl]hydrazine209,22,335(DMSO-d6, 500 MHz) of 7.8 (m, 2H), 4,8 (width, 2H), 4.2V (width, 1H), 3,63 (m, 4H), to 2.29 (m, 4H), to 2.18 (s, 3H) ppm

Scheme 10

Example 12

4-(tert-Butylthiazole-2-yl)hydrazine. A mixture of 1-bromo-3,3-dimethylbutan-2-it (1.35 ml, 10 mmol) and thiosemicarbazide (0,91 g, 10 mmol) in ethanol (35 ml) is refluxed for 1.5 hours and evaporated. Purification with flash chromatography (SiO2) gives 4-(tert-butylthiazole-2-yl)hydrazine (1.01 g, yield 59%) as orange Targovishte. 1H-NMR (DMSO-d6, 500 MHz) 9,0 (width, 1H), and 7.3 (width, 2H), 6,37 (s, 1H), 1,22 (s, N) ppm; MS (LC-MS) 172,1 (M+H); (method A) 2,520 minutes

Similarly receive the following connections:

NameMS (M+N)HPLC, method a1H NMR
(4-Utiltity-2-yl)hydrazine144, 0mm(DMSO-d6, 500 MHz) 8,21 (s, 1H), 6,18 (s, 1H), and 4.68 (s, 2H), 2,44 (kV, 2H), 1,11 (t, 3H) ppm
(4-Cryptomaterial-2-yl)hydrazine184,12,194(DMSO-d6, 500 MHz) of 8.92 (s, 1H), 7,32 (s, 1H), 5,04 (s, 2H) ppm
(4-Phenylthiazol-2-yl)hydrazine166,12,008(DMSO-d6, 500 MHz) 9,0 (width, 1H), to 7.67 (d, 1H), 7,31 (d, 1H), 7,20 (m, 1H), 6,98 (t, 1H), to 5.03 (s, 2H) ppm

Example 13

4,5-Dimethoxy-2-NITROPHENOL. To a solution of 4,5-dimethoxy-2-nitrobenzaldehyde (3.75 g, of 14.2 mmol) in dichloromethane (75 ml) at 0°C in nitrogen atmosphere add metallocarboxypeptidase acid (purity 75%, of 4.90 g, 28.4 mmol), then triperoxonane acid (1,05 ml of 14.2 mmol). The reaction mixture was stirred at room temperature for 18 h, then cooled to 0°C. the Excess reagent is quenched with a 5% solution of sodium bisulfite and the precipitate removed by filtration, washed with dichloromethane. The PR is onicescu phase of the filtrate washed with sodium bicarbonate and a saturated solution of salt, dried (sodium sulfate) and evaporated, thus obtaining a yellow solid. This intermediate compound is suspended in methanol (50 ml), treated with 2 N. NaOH (16 ml, 32 mmol) and stirred at room temperature for 1 hour. The reaction mixture was acidified with 1 N. HCl and filtered, washing with methanol, thus obtaining 4,5-dimethoxy-2-NITROPHENOL (2.00 g, 71%yield) as a bright yellow solid.

1H-NMR (CDCl3, 500 MHz) of 11.0 (s, 1H), 7,39 (s, 1H), 6.48 in (s, 1H), 3,90 (s, 3H), 3,83 (s, 3H) ppm; MS (FIA) 197,9 (M-H); HPLC (method A) 3,357 min

1,2,4-Trimetoksi-5-nitrobenzene. A mixture of 4,5-dimethoxy-2-NITROPHENOL (2.00 g, 10 mmol), potassium carbonate (2.76 g, 20 mmol) and iodomethane (0.75 ml, 12 mmol) in DMF are placed in a sealed tube and heated at 75-80°C for 20 hours. The reaction mixture is cooled and filtered through celite, washing with ethyl acetate. The filtrate is washed with water (water of the first washing back extracted with ethyl acetate, sodium bicarbonate and a saturated salt solution, dried (sodium sulfate) and evaporated. Purification with flash chromatography (SiO2) with elution with a mixture of 1:1 ethyl acetate:hexane gives 1,2,4-trimetoksi-5-nitrobenzene (1.20 g, yield 57%) as a yellow solid.

1H-NMR (CDCl3, 500 MHz) 7,53 (s, 1H), 6,50 (s, 1H), 3,92 (s, 3H), 3,91 (s, 3H), of 3.84 (s, 3H) ppm; MS (FIA) 214,1 (M+H); HPLC (method A) 3,253 min

2,4,5-Trimethoxyphenethylamine. 1,2,4-Trimetoksi-5-nitrobenzene (1.20 g, 5,63 mmol) and chloride dihydrate tin (3,81 g of 16.9 mmol) in ethyl acetate (50 ml) was stirred at 65-70°C for 20 hours. The reaction mixture is cooled, carefully neutralized with sodium bicarbonate and filtered through celite. The organic phase is washed with saturated salt solution, dried (sodium sulfate) and evaporated. Purification with flash chromatography (SiO2) with elution with a mixture of 3:7 ethyl acetate:hexane gives 2,4,5-trimethoxybenzylamine (0.56 g, yield 54%) as a reddish brown solid.1H-NMR (DMSO-d6, 500 MHz) to 6.57 (s, 1H), 6,37 (s, 1H), 3,70 (s, 3H), of 3.65 (s, 3H), 3,63 (s, 3H) ppm; HPLC (method A) 2,163 min

Scheme 11

Example 14

2 Deformedarse-5-NITROPHENOL. A solution of 4-nitrobenzene-1,2-diol (4,18 g, 27,1 mmol), methylchlorothiazide (3.0 ml, 28.5 mmol) and cesium carbonate (11,05 g, to 33.9 mmol) in DMF (75 ml) is heated at 90°C for 24 hours. The reaction mixture is cooled, evaporated and diluted with ethyl acetate. The product is extracted with two times 1 N. NaOH, the combined aqueous phase is acidified, extracted with ethyl acetate (twice) and the organic layers washed with water (twice) and saturated salt solution, dried (sodium sulfate) and evaporated. Purification with flash chromatography (SiO2) with elution with a mixture of 2:8 those who acetate:hexane gives 2-deformedarse-5-NITROPHENOL (1.50 g, yield 27%) as a bright yellow solid.

1H-NMR (DMSO-d6, 500 MHz) of 10.9 (s, 1H), 7,76 (d, 1H), 7,73 (DD, 1H), was 7.36 (d, 1H), 7,28 (m, 1H) ppm; MS (FIA) to 204.1 (M-H); HPLC (method A) 3,307 min

Similarly receive the following connection.

NameRoomMS (M+N)HPLC, method a1H NMR
2 Isopropoxy-5-NITROPHENOLCF#N-3198,13,474(DMSO-d6, 500 MHz) 9,87 (s, 1H), of 7.70 (DD, 1H), 7.62mm (d, 1H), 7,12 (d, 1H), amounts to 4.76 (m, 1H), 1,31 (d, 6N) ppm

1 Deformedarse-2-isopropoxy-4-nitrobenzene. 2 Deformedarse-5-NITROPHENOL (1,49 g, 7,26 mmol), editpopup (0,87 ml 8,72 mmol) and cesium carbonate (3.55 g, 10.9 mmol) in DMF (20 ml) in a sealed tube heated at 90°C for 20 hours. The reaction mixture is cooled and evaporated, diluted with water and extracted twice with ethyl acetate. The combined organic phase washed with water (three times) and saturated salt solution, dried (sodium sulfate) and evaporated, thus obtaining 1-deformedarse-2-isopropoxy-4-nitrobenzene (1,712 g, yield 95%) as an orange oil.

1H-NMR (CDCl3, 500 MHz) to 7.95 (m, 2H), 7,38 (d, 1H), 7,37 (t, 1H), 4,80 (m, 1H), and 1.54 (d, 6N) ppm; MS (FIA) 216,1 (M-H); HPLC (method A) 4,108 min

Similarly receive the following connected the E.

NameRoomMS (M+N)HPLC, method a1H NMR
2 Deformedarse-1 isopropoxy-4-nitrobenzeneCF#N-4218,24,084(CDCl3, 500 MHz) with 8.05 (DD, 1H), 8,00 (d, 1H), 6,95 (d, 1H), of 6.52 (t, 1H)and 4.65 (m, 1H), 1,36 (d, 6N) ppm

4 Deformedarse-3-isopropoxyaniline. The chloride dihydrate tin (5,46 g, and 24.2 mmol) in concentrated HCl (7 ml) at 0°add 1 deformedarse-2-isopropoxy-4-nitrobenzene (1,712 g, 6,92 mmol) in ethyl acetate (7 ml) and the reaction mixture is stirred for 1 hour. The reaction mixture was neutralized to pH ˜7 NaOH and filtered through celite, washing with ethyl acetate. The filtrate are separated and the aqueous phase back extracted with ethyl acetate. The combined organic phase was washed with saturated salt solution, dried (sodium sulfate) and evaporated. Purification with flash chromatography (SiO2) with elution with a mixture of 2:8 ethyl acetate:hexane gives 4-deformedarse-3-isopropoxyaniline (0.55 g, yield 37%, yield 57% based on the selected starting material) as an orange oil.

1H-NMR (CDCl3, 500 MHz) 6,94 (d, 1H), 6,41 (t, 1H), of 6.31 (DD, 1H), 6,23 (d, 1H), 4,47 (m, 1H), 1,33 (d, 6N) ppm; MS (FIA) 218,2 (M+H); HPLC (method A) 2,853 min

Similarly, p is to obtain the following connection.

NameRoomMS (M+N)HPLC, method a1H NMR
2 Deformedarse-4-isopropoxyanilineCF#a-3218,22,827(CDCl3, 500 MHz) of 6.75 (d, 1H), 6,50 (t, 1H), 6,45 (DD, 1H), 4.26 deaths (m, 1H), 1,23 (d, 6N) ppm

Scheme 12

Example 15

4 Methoxybenzo[1,3]dioxol. A mixture of 3-methoxybenzoyl-1,2-diol (1,161 g of 8.28 mmol) in DMF (10 ml) are added to bremgarten (611 μl, 1.1 equivalents) and the mixture was stirred at 90 degrees Celsius for 4 hours. The mixture was poured into water and extracted with dichloromethane. The organic layer was poured through the cartridge separation of the phases and concentrate to dryness. The crude product is a yellow liquid. The clear liquid column chromatography, thus obtaining 1,21 g (96%).

1H-NMR (DMSO, 500 MHz) of 6.7 (t, 1H), 6,63 (d, 1H), return of 6.58 (d, 1H), 5,97 (s, 2H), 3,83 (s, 3H), HPLC (method A) of 2.86 min

Scheme 13

Example 16

4-Methoxy-6-nitrobenzo[1,3]dioxol. 4 Methoxybenzo[1,3]dioxol (2,03 g, 13,34 mmol) dissolved in acetic anhydride (20 ml) and cooled in an ice bath with stirring. The separating funnel is about drops is added nitric acid (1.5 ml) for 30 minutes. The ice bath is removed and the mixture is stirred overnight, allowing the reaction mixture to warm to room temperature. The mixture is then poured into ice water and the product is crushed and filtered and washed with water. The precipitate is dried in vacuum dessicator, while receiving (1,21 g, yield 46%) of 4-methoxy-6-nitrobenzo[1,3]dioxol.

NMR DMSO-d6: 7,63 (s, 1H), 7,52 (s, 1H), and 6.25 (s, 2H), 3,95 (s, 3H)

Scheme 14

Example 17

4-(4-Nitrobenzyl)morpholine. To a mixture of 1-methyl bromide-4-nitrobenzene (5.0 g, of 29.1 mmol) and potassium carbonate (12.0 g, 87 mmol) in THF (100 ml) add a slow stream of research (6,35 ml, 73 mmol). The reaction mixture was stirred 24 hours at room temperature, filtered through celite and evaporated. Purification with flash chromatography (SiO2) gives 4-(4-nitrobenzyl)morpholine (5,27 g, yield 81%) as a pale yellow solid.

1H-NMR (DMSO-d6, 500 MHz) to 8.20 (d, 2H), 7,60 (d, 2H), 3,61 (m, 6N), of 2.38 (m, 4H) ppm; MS (FIA) 223,1(M+H); HPLC (method A) 1,577 min

Similarly receive the following connections:

NameMS (M+N)HPLC, method a1H NMR
1-Methyl-4-(4-nitrobenzyl)-piperazine236,32,202(DMSO-d6, 500 MHz) 8,19 (d, 2H), 7,58 (d, 2H)and 3.59 (s, 2H), 2,35 (Shir. the, 8H), of 2.15 (s, 3H) ppm
4-(4-Nitrobenzyl)-pyrrolidin207,22,262(DMSO-d6, 500 MHz) 8,18 (d, 2H), to 7.59 (d, 2H), 3,71 (s, 2H), 2,45 (m, 4H), 1,71 (m, 4H) ppm
4-(3-Nitrobenzyl)-morpholine223,11,260(DMSO-d6, 500 MHz), 8,17 (s, 1H), 8,13 (d, 1H), 7,78 (d, 1H), to 7.64 (t, 1H), 3,61 (m, 6N), of 2.38 (m, 4H) ppm

4-Morpholine-4-iletilenlerin. According to the procedure described in example 1. that is specified in the header connection receive (1.70 g, yield 98%) as an orange solid.

1H-NMR (DMSO-d6, 500 MHz) 6,91 (d, 2H), of 6.49 (d, 2H), 4.95 points (s, 2H), 3,53 (m, 4H), 2,28 (m, 4H) ppm; MS (FIA) 193,2 (M+H); HPLC (method A) 1,038 minutes

Similarly receive the following connection:

NameMS (M+N)HPLC, method a1H NMR
4-(1-Morpholine-4-retil)phenylamine193,21,493(DMSO-d6, 500 MHz) 6,93 (t, 1H), 6,53 (s, 1H), 6,41 (m, 2H), 5,00 (s, 2H), of 3.56 (m, 4H), 2,31 (m, 4H) ppm

Example 18

4-Pyrrolidin-1-iletilenlerin. Specified in the header of the connection (from 0.37 g, yield 20%) are obtained according to the procedures described above, in the form of a yellow oil.

1H-NMR (DMSO-d6, 500 MHz) 6,92 (d, 2H), of 6.49 (d, 2H), 4,88 (s, 2H), 3,38 (s, 2H), of 2.38 (m, 4H), 1,66 (who, 4H) ppm; MS (FIA) 177,2 (M+H); HPLC (method A) 1,162 minutes

Example 19

4-(4-Methylpiperazin-1-ylmethyl)phenylamine (CF#A-5). A mixture of 1-methyl-4-(4-nitrobenzyl)piperazine (3,09 g of 13.1 mmol), zinc dust (4,29 g, 65,6 mmol) and ammonium chloride (2,81 g of 52.5 mmol) in methanol (100 ml) is refluxed 1 hour, cooled, filtered through celite (washing with methanol) and evaporated, thus obtaining 4-(4-methylpiperazin-1-ylmethyl)phenylamine (2.67 g, yield 99%) as a pale yellow solid.

1H-NMR (DMSO-d6, 500 MHz) 6,89 (d, 2H), of 6.49 (d, 2H), 4,89 (s, 2H), 3,24 (s, 2H), 2,3 (Shir. m, 8H) ppm; MS (FIA) 206,2 (M+H); HPLC (method A), the product eluted with the solvent front.

Example 20

1-(1-Bromacil)-4-nitrobenzene. A mixture of 1-ethyl-4-nitrobenzene (3.4 ml, 25 mmol), N-bromosuccinimide (of 4.38 g, 24.6 mmol) and benzoyl peroxide (0.04 g, 0.18 mmol) in carbon tetrachloride (30 ml) is refluxed 1 hour, cooled and filtered, washing with a mixture of 1:1 ethyl acetate:hexane. The filtrate is evaporated and purified flash chromatography (SiO2) with elution with a mixture of 2:98 ethyl acetate:hexane, while receiving 1-(1-bromacil)-4-nitrobenzene (5,18 g, yield 90%) as a yellow oil.

1H-NMR (CDCl3, 500 MHz) were 8.22 (d, 2H), a 7.62 (d, 2H), 5,22 (square, 1H), 2,08 (d, 3H) ppm; HPLC (method A) 3,837 minutes

4-[1-(4-Nitro the Nile)ethyl]morpholine. A mixture of 1-(1-bromacil)-4-nitrobenzene (1.24 g, 5.43 mmol), potassium carbonate (2.25 g, 16.3 mmol) and research (1.2 ml, to 13.6 mmol) in DMF (10 ml) was stirred at room temperature for 16 h, then evaporated. The residue is suspended in ethyl acetate, washed with water and saturated salt solution, dried (sodium sulfate) and evaporated, thus obtaining 4-[1-(4-nitrophenyl)ethyl]morpholine (1,225 g, yield 95%) as a yellow oil.1H-NMR (DMSO-d6, 500 MHz) 8,19 (d, 2H), 7,16 (d, 2H), of 3.56 (m, 5H), is 2.41 (m, 2H), and 2.26 (m, 2H), of 1.29 (d, 3H) ppm; MS (FIA) 237, 2 (M+H); HPLC (method A) 2,248 minutes

Similarly receive the following connection:

NameMS (M+N)HPLC, method a1H NMR
4-[1-(4-Nitrophenyl)ethyl]-pyrrolidin221,22,359(DMSO-d6, 500 MHz) 8,18 (d, 2H), 7,60 (d, 2H), 3,37 (square, 1H), 2,47 (m, 2H), 2,31 (m, 2H), by 1.68 (m, 4H), of 1.30 (d, 3H) ppm

4-(1-Morpholine-4-retil)phenylamine. Specified in the title compound is obtained by a method described above.

1H-NMR (DMSO-d6, 500 MHz) of 6.90 (d, 2H), of 6.49 (d, 2H), to 4.87 (s, 2H), 3,51 (m, 4H), 3,14 (square, 1H), 2,30 (m, 2H), 2,25 (m, 2H), 1,21 (d, 3H) ppm; MS (FIA) 207,3 (M+H).

Similarly receive the following connection:

NameMS (M+N)VE IS X, method And1H NMR
4-(1-Pyrrolidinyl-ethyl) - phenylamine191,3(DMSO-d6, 500 MHz) 6,93 (d, 2H), 6.48 in (d, 2N), a 4.86 (s, 2H), 3,1 (m, 1H), 2,45 (m, 2H), to 2.29 (m, 2H), 1,64 (m, 2H), 1,21 (d, 3H) ppm

Example 21

2-Methoxy-4-morpholino-4-elfenlied. To a suspension of 5-morpholino-2-nitroanisole (0,76 g is 3.21 mmol) in Meon (20 ml) in an atmosphere of N2add 5% Pd/C. the Reaction mixture was stirred in an atmosphere of H2at room temperature for 4 h, filtered through celite, which is washed with Meon. The filtrate was concentrated in vacuo, while receiving the product as a sticky red solid (0,63 g, yield 95%).

NameMS (M+N)HPLC, method a1H NMR
2-Methoxy-4-morpholino-4-elfenlied209,15 (method)(DMSO-d6, 500 MHz): of 6.52 (d, 1H), 6,50 (d, 1H), 6,28 (DD, 1H), 4,23 (s,2H), 3,80-the 3.65 (m, 7H), 2.95 and-2,90 (m, m, 4H)
Indan-4-ylamine2,72

(method A)
(CDCl3, 500 MHz): 6,97 (t, 1H), of 6.68 (d, 1H), 6.48 in (d, 1H), 3,54 (Shir. s, 2H), 2,90 (t, 2H), 2,71 (t, 2H), 2,20-of 1.97 (m, 2H)
7 Methoxybenzo-[1,3]dioxol-5-ylamine168,05

Scheme 15

Example 22

Methyl ester 2-chloro-4-fermenting acid. A mixture of 2-chloro-4-fermenting acid (6.5 g, 37 mmol) in methanol (100 ml) is treated with chlorotrimethylsilane (14,0 ml, 111 mmol), stirred for 24 hours at room temperature and evaporated. The residue is dissolved in dichloromethane, washed with sodium bicarbonate, dried (sodium sulfate) and evaporated, thus obtaining methyl ester 2-chloro-4-fermenting acid (7.01 g, yield 99%) as a pale yellow oil.

1H-NMR (CDCl3, 500 MHz) to 7.93 (m, 1H), 7,22 (m, 1H), 7,06 (m, 1H), 3,95 (s, 3H) ppm; MS (FIA) 189,1 (M+H); HPLC (method A) 3,37 minutes

Methyl ester of 3,5-dimethoxy-4-(2-morpholine-4-ylethoxy)benzoic acid. To a solution of methyl 3,5-dimethoxy-4-hydroxybenzoate (3.0 g, 14 mmol) in DMF (10 ml) was added the hydrochloride of 4-(2-chloroethyl)of the research (3,99 g, 21 mmol) and solid To2CO3(of 8.4 g, 60 mmol). The mixture is heated at 60°C in an atmosphere of N2within 30 hours. The mixture is diluted with EtOAc (100 ml) and washed with H2About (2 × 50 ml), back extracted aqueous phase and the combined organic phases are washed with a saturated solution of salt. The organic layer is dried over Na2SO4, filtered and evaporated, thus obtaining the product as a brown solid (4.9 g, yield quantitative).

1H-NMR (CDCl3, 500 MHz) 7,28 (s, 2H), 4,15 (t, 2H), 3,91 (s, 3H), 3,88 (C, 6N), 3.75 to 3,71 (m, 4H), 2,78 (t, 2H), 2,59 (Shir. s, 4H) ppm; MS (FIA) 326,17 (M+N)

Similarly receive the following connection:

NameMS (M+N)Retention time (min)1H NMR
Methyl ester of 4-isopropoxy-3,5-dimethoxybenzoic acid25,133,38(DMSO-d6, 500 MHz) of 7.24 (s, 2H), 4,45-4,32 (m, 1H), 3,85 (s, 3H), 3,81 (C, 6N), of 1.18 (d, 6N)

Methyl ester 2-chloro-4-morpholine-4-eventing acid. A mixture of methyl ester of 2-chloro-4-fermenting acid (3.51 g, to 18.6 mmol), research (1,95 ml of 22.3 mmol) and potassium carbonate (5,12 g, 37,1 mmol) in N-organic (20 ml) was stirred at 120°C for 5 hours. The reaction mixture is cooled, diluted with ethyl acetate and filtered through celite. The filtrate is washed four times with water, once with saturated salt solution, dried (sodium sulfate) and evaporated. Purification with flash chromatography (SiO2) with elution with a mixture of 2:8 ethyl acetate:hexane gives the methyl ester of 2-chloro-4-morpholine-4-eventing acid (is 3.08 g, yield 65%) as a white solid.

1H-NMR (CDCl3, 500 MHz) 7,79 (d, 1H), for 6.81 (d, 1H), to 6.67 (DD, 1H), 3,81 (s, 3H), of 3.78 (m, 4H), 3,20 (m, 4H) ppm; MS (FIA)256,1 (M+H); HPLC (method A) 3,275 minutes

Tert-Butyl ether (2-chloro-4-morpholine-4-ylphenyl)carbamino acid. A mixture of methyl ester of 2-chloro-4-morpholine-4-eventing acid (is 3.08 g, 12,0 mmol) and 6 N. NaOH (2.5 ml, 15 mmol) in methanol (50 ml) and water (7.5 ml) is stirred 24 hours at room temperature, then acidified with 2 N. HCl. The precipitate is filtered off, washed with water and dried, thus obtaining 2-chloro-4-morpholine-4-eventing acid (2,56 g, yield 88%) as a white solid. This solid (10.6 mmol) is suspended in tert-butanol (20 ml), treated with diphenylphosphorylacetate (2.30 ml, 10.6 mmol), then triethylamine (1,45 ml, 10.6 mmol), stirred at the boil under reflux for 20 h and evaporated. Purification with flash chromatography (SiO2) with elution with a mixture of 2:8 ethyl acetate:hexane gives tert-butyl ether (2-chloro-4-morpholine-4-ylphenyl)carbamino acid (2,84 g) in a mixture (˜ 1:1) with the tert-butyl ester 2-chloro-4-morpholine-4-eventing acid. This mixture is used without further purification.

1H-NMR (CDCl3, 500 MHz) 8,0 (width, 1H), 7,80 (d, 1H), and 7.4 (d, 1H), 6.90 to (d, 1H), 6.87 in (d, 1H), 6,84 (DD, 1H), 6.75 in (DD, 1H), a 3.87 (m, 8H), 3,26 (m, 4H), 3,11 (m, 4H), to 1.61 (s, N), of 1.55 (s, N) ppm; MS (FIA) 313,1 (M+H); HPLC (method A) 3,70 minutes

In a similar way we obtain the following connections:

NameMS (M+N)The HPLC retention time (min)1H NMR
Tert-butyl ether [3,5-dimethoxy-4-(2-morpholine-4-ylethoxy)phenyl]-carbamino acid383,21,9(DMSO-d6, 500 MHz): of 9.21 (s, 1H), PC 6.82 (s, 2H), a 3.87 (t, 2H), 3,69 (C, 6N), of 3.56 (t, 4H), 2,62-2,39 (m, 6N), of 1.46 (s, N)
Benzyl ether of 4-(4-tert-butoxycarbonylamino-2,6-dimethoxyphenoxy)-piperidine-1-carboxylic acid487,3

2-Chloro-4-morpholine-4-elfenlied. A solution of impure tert-butyl ether (2-chloro-4-morpholine-4-ylphenyl)carbamino acid (2,84 g) in dichloromethane (30 ml) is treated triperoxonane acid (3.5 ml), stirred at room temperature for 24 hours and evaporated. The residue is dissolved in ethyl acetate, washed with 1 N. NaOH, water and saturated salt solution, dried (sodium sulfate) and evaporated. Purification with flash chromatography (SiO2) with elution with a mixture of 35:65 ethyl acetate:hexane gives 2-chloro-4-morpholine-4-elfenlied (0,77 g, yield 40%) as not quite white solid.

1H-NMR (CDCl3, 500 MHz) 6,92 (width, 1H), 6,77 (width, 2H), with 3.89 (m, 6N), was 3.05 (m, 4H) ppm; MS (FIA) 213,1 (M+H); HPLC (method A) 1,975 minutes

Example 23

Benzyl ether of 4-(4-amino,6-dimethoxyphenoxy)piperidine-1-carboxylic acid. Specified in the title compound is obtained from the benzyl ester of 4-(4-tert-butoxycarbonylamino-2,6-dimethoxyphenoxy)piperidine-1-carboxylic acid by the procedure described in example ST-3. MS (ES+): m/z=387,2.

Example 24

tert-Butyl ester 4-(4-AMINOPHENYL)piperazine-1-carboxylic acid. Specified in the title compound is obtained from 4-iodoaniline and tert-butyldimethylchlorosilane according to the procedure described in example ST-1. MS (ES+): m/z=278,2.

Example 25

tert-Butyl ester 4-(4-aminobenzoyl)piperazine-1-carboxylic acid. To a solution of 4-aminobenzoic acid (411 mg, 3.00 mmol) in DMF (3.0 ml) at room temperature add EDC (862 mg, 4,50 mmol), HOBt (608 mg, 4,50 mmol), triethylamine (606 mg; 0,835 ml of 6.00 mmol) and tert-butylpiperazine (671 mg, of 3.60 mmol). The mixture is stirred for 22 h, then add 2 N. aqueous NaOH to establish a pH>10. The mixture is extracted with ethyl acetate and the organic layer is dried over MgSO4concentrate. The residue is purified column chromatography on silica gel with elution with a mixture of EtOAc:hexane (from 50 to 90% EtOAc), while receiving tert-butyl ester 4-(4-aminobenzoyl)piperazine-1-carboxylic acid (796 mg, 87%) as a colourless oil. MS (ES+): m/z=306,2.

Example 26

1-Cyclopropyl-4-(4-nitrophen is)piperazine. To a solution of 1-(4-nitrophenyl)piperazine (1.04 g, 5.00 mmol) in methanol (25 ml) under nitrogen atmosphere add molecular sieves (1.0 g), acetic acid (3.00 g, of 2.86 ml, 50.0 mmol) [(1-amoxicilpin)oxy]trimethylsilane (5,22 g of 5.99 ml, 30.0 mmol), cyanoborohydride sodium (1,41 g of 22.5 mmol). The mixture is stirred at room temperature for 2.5 hours, filtered and concentrated. To the residue add water and 1 N. aqueous NaOH to regulate the pH to >11. The mixture is extracted with ethyl acetate and the organic layer dried over Na2SO4concentrate, while receiving specified in the title compound (1.24 g, 100%) as a yellow solid. MS (ES+): m/z=247,8.

Example 27

4-(4-Cyclopropylmethyl-1-yl)phenylamine. To a solution of 1-cyclopropyl-4-(4-nitrophenyl)piperazine (1.24 g, 5.00 mmol) in methanol (25 ml) is added Pd/C (10%, 100 mg) and triperoxonane acid (1.0 ml). The mixture is stirred under hydrogen pressure (balloon) 1 ATM over night, filtered and concentrated. To the residue add water and 1 N. aqueous NaOH to regulate pH >11. The mixture is extracted with ethyl acetate and the organic layer dried over Na2SO4concentrate, while receiving specified in the title compound (1.08 g, 100%) as a brown oil. MS (ES+) m/z=218,1

Example 28

CIS-2,6-Dimethyl-4-(4-nitrophenyl)mo is Olin. A mixture of 1-fluoro-4-nitrobenzene, 2,6-dimethylmorpholine (purchased from Aldrich) and Diisopropylamine heated at 110°C for 16 hours. After cooling to room temperature the mixture was added water and extracted with EtOAc. The organic phase is dried over MgSO4concentrate. The residue is purified column chromatography on silica gel with elution with a mixture of EtOAc:hexane (from 5 to 35% EtOAc), while receiving TRANS-2,6-dimethyl-4-(4-nitrophenyl)novolin (258 mg) and CIS-2,6-dimethyl-4-(4-nitrophenyl)novolin (838 mg), both as yellow solids. TRANS-isomer: MS (ES+): m/z=USD 237.2;1H-NMR (CDCl3, 500 MHz): δ of 1.30 (d, 6N), 3,17 (DD, 2H), 3.46 in (DD, 2H), 4,15-4,22 (m, 2H), 6,77 (d, 2H), 8,14 (d, 2H).CIS-isomer: MS (ES+): m/z=USD 237.2;1H-NMR (CDCl3, 500 MHz): δ of 1.29 (d, 6N), 2,62 (DD, 2H), to 3.67 (DD, 2H), of 3.73-3,81 (m, 2H), at 6.84 (d, 2H), 8,14 (d, 2H).

Example 29

4-(2,6-Dimethylmorpholine-4-yl)phenylamine. Specified in the title compound is obtained from CIS-2,6-dimethyl-4-(4-nitrophenyl)the research on the procedure described above. MS (ES+): m/z=207,3

Example 30

2-(4-Nitrophenylamino)ethanol. Specified in the title compound is obtained from 1-fluoro-4-nitrobenzene and 2-aminoethanol according to the procedure described above.

MS (ES+): m/z=USD 183.0;1H-NMR (CDCl3, 500 MHz): δ to 3.41 (t, 2H), 3,92 (t, 2H), 6,59 (d, 2H), 8,11 (d, 2H).

Example 31

Scheme 16

Example 32

1-(2-Chloroethoxy)-2-methoxy-4-nitrobenzene. A mixture of 2-methoxy-4-NITROPHENOL (2.50 g, of 14.8 mmol), 1-bromo-2-chlorethane (1.35 ml, 16.3 mmol) and potassium carbonate (4,08 g, 19,6 mmol) in DMF (50 ml) in a sealed tube heated at 90°C for 18 hours. The reaction mixture is cooled and filtered, washing with ethyl acetate. The filtrate is washed with sodium bicarbonate, water (4 times) and saturated salt solution and dried (sodium sulfate) and evaporated. Purification with flash chromatography (SiO2) with elution with a mixture of 35:65 ethyl acetate:hexane gives 1-(2-chloroethoxy)-2-methoxy-4-nitrobenzene (1,93 g, yield 56%) as not quite white solid.

1H-NMR (DMSO, 500 MHz): 7,89 (DD, 1H), 7,76 (d, 1H), 7,21 (d, 1H), to 4.41 (t, 2H), 4.00 points (t, 2H), 3,90 (s, 3H) ppm; HPLC (method A) 3,781 minutes

In a similar way we obtain the following connections:

NameMS (M+N)The HPLC (min)1H NMR
1-(4-Chloroethoxy)-2-methoxy-4-nitrobenzene4,204(DMSO-d6, 500 MHz) of 7.9 (DD, 1H), of 7.75 (d, 1H), 7,2 (d, 1H), 4,15 (t, 2H), 3,9 (s, 3H), of 3.75 (t, 2H), and 1.9 (m, 4H) ppm
1-(3-Bromopropane)-2-methoxy-4-nitrobenzene4,121(DMSO-d6,500 MHz) of 7.90 (DD, 1H), of 7.75 (d, 1H), 7,22 (d, 1H), 4,23 (t, 2H), with 3.89 (s, 3H), 3,66 (t, 2H), 2,30 (m, 2H) ppm
1-(3-Chloropropoxy)-2-methoxy-4-nitrobenzene3,843(DMSO-d6, 500 MHz) 7,89 (DD, 1H), of 7.75 (d, 1H), 7,21 (d, 1H), 4,24 (t, 2H), with 3.89 (s, 3H), 3,79 (t, 2H), 2,22 (m, 2H) ppm
Benzyl ether of 4-(2,6-dimethoxy-4-methoxycarbonylbenzyl)-piperidine-1-carboxylic acid430,3

4-[2-(2-Methoxy-4-nitrophenoxy)ethyl]morpholine. A mixture of 1-(2-chloroethoxy)-2-methoxy-4-nitrobenzene (0,60 g at 2.59 mmol), research (of 0.28 ml, 3.11 mmol), sodium iodide (0.39 g, at 2.59 mmol) and potassium carbonate (0.71 g, 5.18 mmol) in ethanol (5 ml) is heated in a sealed tube at 90°C for 18 h, cooled, filtered and evaporated. Purification with flash chromatography (SiO2) with elution with a mixture of 2:98 methanol:dichloromethane gives 4-[2-(2-methoxy-4-nitrophenoxy)ethyl]morpholine (0,37 g, 51%yield) as a pale yellow solid.1H-NMR (DMSO-d6, 500 MHz) 7,89 (DD, 1H), 7,74 (d, 1H), 7,21 (d, 1H), 4,23 (t, 2H), 3,88 (s, 3H), 3,88 (m, 4H), by 2.73 (t, 2H), 2,50 (m, 4H) ppm; MS (FIA) 283,2 (M+H); HPLC (method A) 2,652 minutes

Similarly receive the following connections:

NameMS (M+is) HPLC, method a1H NMR
4-[4-(2-Methoxy-4-nitrophenoxy)butyl]-morpholine311,1(DMSO-d6, 500 MHz) 7,89 (DD, 1H), 7,73 (d, 1H), 7,18 (d, 1H), 4,13 (t, 2H), 3,88 (s, 3H), 3,55 (m, 4H), 2,32 (m, 6N), of 1.78 (m, 2H), 1.57 in (m, 2H) ppm
Diethyl-[2-(2-methoxy-4-nitrophenoxy)ethyl]-Amin269,22,588(DMSO-d6, 500 MHz) 7,89 (DD, 1H), 7,73 (d, 1H), 7,20 (m, 1H), 4,15 (t, 2H), 3,88 (s, 3H), of 2.81 (t, 2H), 2,55 (square, 4H), of 0.97 (t, 6N) ppm
1-[3-(2-Methoxy-4-nitrophenoxy)propyl]-1H-imidazol278,12,601(DMSO-d6, 500 MHz) 7,79 (DD, 1H), 7,76 (d, 1H), 7,76 (s, 1H), 7,20 (s, 1H), 7,15 (d, 1H), 6.89 in (s, 1H), 4,13 (t, 2H), of 4.05 (t, 2H), 3,91 (s, 3H), of 2.23 (m, 2H) ppm
Diethyl-[3-(2-methoxy-4-nitrophenoxy)propyl]-amine283,22,811(DMSO-d6, 500 MHz) 7,88 (DD, 1H), 7,73 (d, 1H), 7,17 (d, 1H), 4,15 (t, 2H), 3,88 (s, 3H), of 2.50 (m, 2H), 2,44 (square, 4H), of 1.85 (m, 2H), 0,93 (t, 6N) ppm
4-[3-(2-Methoxy-4-nitrophenoxy)propyl]-2,6-dimethylmorpholine325,12,962(DMSO-d6, 500 MHz) 7,89 (DD, 1H), 7,73 (d, 1H), 7,17 (d, 1H), 4,15 (t, 2H), 3,88 (s, 3H), 3,53 (m, 2H), 2,74 (d, 2H), 2,39 (t, 2H), 1,92 (m, 2H), 1.57 in (t, 2H), 1,04 (d, 6N) ppm
4-[3-(2-Methoxy-4-nitrophenoxy)propyl]-morpholine297,12,574(DMSO-d6, 500 MHz) 7,89 (DD, 1H), 7,73 (d, 1H), 7,18 (d, 1H), 4,15 (t, 2H), 3,88 (s, 3H), of 3.57 (m, 4H), 2,41(t, 2H), a 2.36 (m, 4H), of 1.92 (m, 2H) ppm

3-Methoxy-4-(2-morpholine-4-ylethoxy)phenylamine. Specified in the header connection get the procedure described above, in the form of a red oil (0.14 g, yield 43%).

1H-NMR (DMSO-d6, 500 MHz) of 6.65 (d, 1H), 6,24 (d, 1H), 6,03 (DD, 1H), 4,70 (s, 2H), a 3.87 (t, 2H), 3,66 (s, 3H), of 3.56 (m, 4H), 2,58 (t, 2H), 2,44 (m, 4H) ppm; MS (FIA) 253,2 (M+H); HPLC (method A) the product eluted with the solvent front.

Similarly receive the following connections:

NameMS (M+N)HPLC, method a1H NMR
3-Methoxy-4-(3-morpholine-4-ylpropionic)phenylamine267,22,746(DMSO-d6, 500 MHz) 6,62 (d, 1H), 6,24 (d, 1H), 6,03 (DD, 1H), and 4.68 (s, 2H), 3,80 (t, 2H), 3,66 (s, 3H), of 3.56 (m, 4H), of 2.38 (t, 2H), 2,34 (m, 4H), to 1.76 (m, 2H) ppm
4-[3-(2,6-Dimethylmorpholine-4-yl)propoxy]-3-methoxybenzylamine295,22,229(DMSO-d6, 500 MHz) 6,62 (d, 1H), 6,24 (d, 1H), 6,03 (DD, 1H), and 4.68 (s, 2H), 3,79 (t, 2H), 3,66 (s, 3H), 3,52 (m, 4H), of 2.72 (d, 2H), a 2.36 (t, 2H), 1,76 (m, 2H), and 1.56 (t, 2H), of 1.03 (d, 6H) ppm
4-(3-Diethylaminopropyl)-3-methoxybenzylamine253,2USD 2.075(DMSO-d6, 500 MHz) 6,63 (d, 1H), and 6.25 (d, 1H), 6,04 (DD, 1H), 4,70 (s, 2H), 3,82 (t, 2H), 3,66 (s,3H), 2,6 (Shir. m, 6H), 1.8 m (Shir. m, 2H), 1.00 m (Shir. m, 6H) ppm
4-(3-Imidazol-1-Elpro is hydroxy)-3-methoxybenzylamine 248,21,681(DMSO-d6, 500 MHz) to 7.61 (s, 1H), 7,18 (s, 1H), to 6.88 (s, 1H), only 6.64 (d, 1H), of 6.26 (d, 1H), 6,04 (DD, 1H), to 4.73 (s, 2H), 4,11 (t, 2H), 3,70 (t, 2H), 3,68 (s, 3H), 2,04 (m, 2H) ppm
4-(2-Diethylaminoethoxy)-3-methoxybenzylamine239,22,190(DMSO-d6, 500 MHz) only 6.64 (d, 1H), 6,24 (d, 1H), 6,03 (DD, 1H), and 4.68 (s, 2H), 3,81 (t, 2H), 3,66 (s,3H), to 2.67 (m, 2H), 2,5 (m, 4H), of 0.95 (t, 6H) ppm
3-Methoxy-4-(4-(morpholine-4-albucosi)phenylamine283,2(DMSO-d6, 500 MHz) 6,62 (d, 1H), 6,24 (d, 1H), 6,03 (DD, 1H), 4,67 (s, 2H), of 3.78 (t, 2H), 3,66 (s,3H), 3,55 (m, 4H), 2,28 (t, 2H), 2,32 (m, 4H), of 1.62 (m, 2H), 1,53 (m, 2H) ppm

Scheme 17:

Tert-Butyl ether [3-(2-chloroethoxy)-4,5-acid]carbamino acid. 3-(2-Chloroethoxy)-4,5-dimethoxybenzoic acid (500 mg, 1.9 mmol), DPPA (550 mg, 2 mmol) and tea (2 mmol) are mixed in 5 ml of tert-butanol and refluxed for 5 hours. tert-butanol is removed under vacuum and the residue purified by chromatography on silica gel (5% methanol/DCM), while receiving tert-butyl ester of [3-(2-chloroethoxy)-4,5-acid]carbamino acid.

NMR CDCl3: 6,7 (d, 2H), 6,4 (Sirs, 1H), 4,3 (t, 3H), 3,85 (s, 3H), of 3.80 (s, 3H), 3,82 (m, 2H), 1,5 (, N).

tert-Butyl ether [3,4-dimethoxy-5-(2-morpholine-4-ylethoxy)phenyl]carbamino acid. tert-Butyl ether [3-(2-chlore is hydroxy)-4,5-acid]carbamino acid (90 mg, 0.27 mmol) in 1 ml of ethanol is treated with 200 μl of the research and refluxed for 18 hours. The solvent and excess of the research is evaporated and the residue purified preparative TLC, while receiving 79 mg tert-butyl ether [3,4-dimethoxy-5-(2-morpholine-4-ylethoxy)phenyl]carbamino acid. MS ES+ 383.

3,4-Dimethoxy-5-(2-morpholine-4-ylethoxy)phenylamine.

tert-Butyl ether [3,4-dimethoxy-5-(2-morpholine-4-ylethoxy)phenyl]carbamino acid (97 mg, 0.24 mmol) is stirred in 1 ml of DCM and 1 ml of TFA. Later ˜1 hour TFA and DCM is evaporated and add 2 ml of saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with DCM, which is evaporated, while receiving 60 mg of 3,4-dimethoxy-5-(2-morpholine-4-ylethoxy)phenylamine. MS ES+ 283,1.

Similar methods have received the following anilines:

NameMS (M+N)
3-(2-Dimethylaminoethoxy)-4,5-dimethoxyphenyl241,1
3-(2-Diethylaminoethoxy)-4,5-dimethoxyphenyl269,2
3-[2-(2,6-Dimethylmorpholine-4-ylethoxy]-4,5-dimethoxyphenyl311,2
3,4-Dimethoxy-5-[2-(4-methylpiperazin-1-yl)ethoxy]phenylamine296,2
3-(2-Imidazol-1-ylethoxy)-4,5-dimethoxyphenyl 264,1
3,4-Dimethoxy-5-(3-morpholine-4-ylpropionic)phenylamine297,2
3-(3-Dimethylaminopropoxy)-4,5-dimethoxyphenyl255,2

Example 33

Methyl ester of 4-(3-chloropropoxy)for 3,5-dimethoxybenzoic acid. Specified in the header connection get the procedure described above.

1H-NMR (CDCl3, 500 MHz) 7,22 (s, 2H), 4,11 (t, 2H), of 3.84 (s, 3H), 3,83 (C, 6N), of 3.78 (t, 2H), 2,11 (m, 2H) ppm; HPLC (method A) 4,060 minutes

Similarly receive the following connections:

NameMS (M+N)HPLC, method a1H NMR
Methyl ester of 4-(4-chloroethoxy)for 3,5-dimethoxybenzoic acid4,227(CDCl3, 500 MHz) to 7.32 (s, 2H), 4.09 to (t, 2H), of 3.94 (s, 3H), 3,92 (C, 6N), 3,68 (t, 2H), and 2.7 (m, 2H), 1,92 (m, 2H) ppm
Methyl ester 3-(2-chloroethoxy)-4,5-dimethoxybenzoic acidNMR CDCl3: to 7.35 (s, 1H), 7,30 (s, 1H), 4,35 (t, of 3.95 (s, 3H), 3,90 (C, 6N), 3,85 (t, 2H)

tert-Butyl ester [4-(3-chloropropoxy)for 3,5-acid]carbamino acid. Specified in the header connection get the procedure described in example C

1The NMR (CDCl 3, 500 MHz) to 6.58 (s,2H), 6.35mm (s, 1H), 3,98 (t, 2H), of 3.77 (t, 2H), 3.75 to (C, 6N), of 2.08 (m,2H), 1,44 (s, N) ppm; MS (FIA) 246,1 (M+H-BOC); HPLC (method A) at 4,301 minutes

Similarly receive the following connections:

NameMS (M+H-BOC)HPLC, method a1H NMR
Tert-Butyl ester [4-(4-chloroethoxy)for 3,5-acid]-carbamino acidof 260.24,394(CDCl3, 500 MHz) to 6.57 (s, 2H), 6.35mm (s, 1H), 3,86 (t, 2H), 3.75 to (C, 6N), to 3.58 (t, 2H), 2,01 (m, 2H), 1,79 (m, 2H), 1,44 (s, N) ppm
Tert-Butyl ether [3-(2-chloroethoxy)-4,5-acid]-carbamino acidNMR CDCl3: 6,7 (d, 2H), 6,4 (Sirs, 1H), 4,3 (t, 3H), 3,85 (s, 3H), of 3.80 (s, 3H), 3,82 (m, 2H), 1,5 (, N)

tert-Butyl ether [3,5-dimethoxy-4-(3-morpholine-4-ylpropionic)phenyl]carbamino acid. Specified in the header connection get the procedure described above.

1H-NMR (DMSO-d6, 500 MHz) of 9.2 (s, 1H), PC 6.82 (s, 2H), 3,80 (t, 2H), 3,69 (C, 6N), of 3.56 (m, 4H), 2,42 (t, 2H), 2,33 (m, 4H), 1,72 (m, 2H), 1,46 (s, N) ppm; MS (FIA) 397,2 (M+H); HPLC (method A) 3,049 minutes

Similarly receive the following connections:

NameMS (M+N)HPLC, method a H NMR
tert-Butyl ester {4-[3-(2,6-dimethylmorpholine-4-yl)propoxy] - for 3,5-acid}-carbamino acid425,33,346(DMSO-d6, 500 MHz) 9,20 (s, 1H), PC 6.82 (s, 2H), 3,79 (t, 2H), 3,69 (C, 6N), 3,51 (m, 2H), 2,70 (d, 2H), 2,39 (t, 2H), 1,71 (m, 2H), and 1.56 (m, 2H), 1,46 (s, N), of 1.03 (d, 6N) ppm
tert-Butyl ester [4-(3-diethylaminopropyl)for 3,5-acid]-carbamino acid383,33,296(DMSO-d6, 500 MHz) of 9.2 (s, 1H), PC 6.82 (s, 2H), 3,79 (t, 2H), 3,69 (C, 6N), of 2.50 (m, 2H), 2,43 (kV, 4H), of 1.66 (m, 2H), 1,46 (s, N), of 0.93 (t, 6N) ppm
tert-Butyl ether {3,5-dimethoxy-4-[3-(4-methylpiperazin-1-yl)propoxy]phenyl}-carbamino acid410,32,916(DMSO-d6, 500 MHz) of 9.2 (s, 1H), PC 6.82 (s, 2H), of 3.78 (t, 2H), 3,69 (C, 6N), is 2.40 (t, 2H), 2,3 (m, 8H), to 2.13 (s, 3H), of 1.70 (m, 2H), 1,46 (s, N) ppm
tert-Butyl ester of 3,5-dimethoxy-4-(4-(morpholine-4-yl)butoxy)phenyl]-carbamino acid411,33,183(DMSO-d6, 500 MHz) of 9.2 (s, 1H), PC 6.82 (s, 2H), 3,76 (t, 2H), 3,69 (C, 6N), of 3.56 (m, 4H), 2,32 (m, 4H), 2,28 (t, 2H), 1.57 in (m, 4H), of 1.46 (s, N) ppm
tert-Butyl ester [4-(4-Diethylaminoethoxy)for 3,5-acid]-carbamino acid397,33,328(DMSO-d6, 500 MHz) of 9.2 (s, 1H), PC 6.82 (s, 2H), 3,76 (t, 2H), 3,69 (C, 6N), 2,42 (kV, 4H), of 2.36 (t, 2H), 1.55V (m, 2H), 1,50 (m, 2H), 1,46 (s, N), of 0.93 (t, 6N) ppm
Tr is t-Butyl ether (2,3,4-trioxifene)-carbamino acid 326,24,25
tert-Butyl methyl ether (3-ethoxy-4-methoxyphenyl)-carbamino acid268,1
tert-Butyl ether (2,3,4-trimethoxyphenyl)-carbamino acid284,13,75
tert-Butyl ether [3-(3-chloropropoxy)-4,5-acid)carbamino acid346,04,07
tert-Butyl ester [4-(3-bromopropane)for 3,5-acid)carbamino acid390,044,10
tert-Butyl ether (2,3,4-trioxifene)-carbamino acid326,24,25
tert-Butyl methyl ether (3-ethoxy-4-methoxyphenyl)-carbamino acid268,1
tert-Butyl ether (2,3,4-trimethoxyphenyl)-carbamino acid284,13,75
tert-Butyl ether [3-(3-chloropropoxy)-4,5-acid)carbamino acid346,04,07
tert-Butyl ester [4-(3-bromopropane)for 3,5-acid)carbamino acid390,044,10#x0200A;
tert-Butyl ether (2,3,4-trioxifene)-carbamino acid326,24,25
tert-Butyl methyl ether (3-ethoxy-4-methoxyphenyl)-carbamino acid268,1
tert-Butyl ether (2,3,4-trimethoxyphenyl)-carbamino acid284,13,75
tert-Butyl ether [3-(3-chloropropoxy)-4,5-acid]-carbamino acid346,04,07
tert-Butyl ester [4-(3-bromopropane)for 3,5-acid]-carbamino acid390,044,10
tert-Butyl ether (2,3,4-trioxifene)-carbamino acid326,24,25

3,5-Dimethoxy-4-(3-morpholine-4-ylpropionic)phenylamine. Specified in the header connection get the procedure described above. Specified in the header of the connection used in the raw form and not analyze.

Similarly receive the following connections:

Name
4-[3-(2,6-Dimethylmorpholine-4-yl)propoxy] - for 3,5-dimethoxyaniline
4-(3-Diethylaminopropyl)for 3,5-dimethoxyaniline
Dimethoxy-4-[3-(4-methylpiperazine]phenylamine
3,5-Dimethoxy-4-(4-(morpholine-4-albucosi)phenylamine
4-(4-Diethylaminoethoxy)for 3,5-dimethoxyaniline

Scheme 18:

2-Fluoro-5-morpholine-4-elfenlied

To a solution of 2-fluoro-5-nitrophenylamino (4.68 g, 30 mmol), triethylamine (13,8 ml, 100 mmol) in dichloromethane (100 ml) is added dropwise at 0°triperoxonane anhydride (5.7 ml, 40 mmol). After 1 hour the reaction mixture is washed with water, dilute HCl (pH 2) and water, concentrated, thus obtaining the crude 2,2,2-Cryptor-N-(2-fluoro-5-nitrophenyl)ndimethylacetamide (12.9 g).

Crude ndimethylacetamide dissolved in EtOAc (50 ml), shaken with 10% Pd/C (450 mg) in an atmosphere of H2(50 psi). Filtering gives N-(5-amino-2-forfinal)-2,2,2-triptorelin (8,42 g).

A mixture of aniline (1.5 g, 6.7 mmol), bis-(2-bromatologia) ester (1.5 g, 6.7 mmol), diisopropylethylamine (4,7 ml, 31 mmol) in a mixture of toluene (100 ml) and dimethylacetamide (DMA, 5 ml) is refluxed for 5 days. Concentration and column chromatography (hexane/EtOAc, 7:3) to give 2,2,2-Cryptor-N-(2-fluoro-5-morpholine-4-ylphenyl)ndimethylacetamide (1.45 g). LC-MS: m/e=291,1 (M-N), 293,2 (M+H). 1H-NMR (DMSO-d6, 500 MHz) 11,19 (s, 1H), 7,20 (m, 1H), 6,98 (DD, 1H), 6,94 (dt, 1H), and 3.72 (t, 4H), 3,06 (t, 4H).

Scheme 19

5-Morpholine-4-yl-4-nitro-2-cryptomaterial. At -10°With 90% fuming nitric acid (25 ml) is slowly added to concentrated sulfuric acid (50 ml)to maintain the temperature below 0°C. At -20°add portions of 1-fluoro-4-cryptomaterial (5 g, 27.7 mmol), in order to maintain the temperature of the reaction mixture below 0°C. After the addition the reaction mixture was kept at 0°C for 30 min, poured into a mixture of ice-water, extracted with EtOAc. The extracts are concentrated, thus obtaining a mixture (6,05 g) 4-fluoro-2-nitro-1-cryptomaterial and 1-fluoro-2-nitro-4-cryptomaterial in the ratio of 3:1. The crude nitration product (6,05 g) dissolved in ethanol (40 ml) and shaken with 10% Pd/C (310 mg) and concentrated HCl (2.8 ml) in an atmosphere of H2(50 psi) for 3.5 hours. Filtration and concentration to give a mixture (8.0 g) 5-fluoro-2-triphtalocyaninine and its isomer 2-fluoro-5-triphtalocyaninine in the ratio of 3:1. Without cleaning phenylamine (7 g, 35.8 mmol) suspended in dichloromethane (100 ml), treated triperoxonane anhydride (71 mmol) and triethylamine (20 ml) for 16 hours. The reaction mixture was washed with saturated NaHCO3and a saturated solution of salt. The organic phase is further purified by chromatography on silica gel (hexane/EtOAc, 9:1), thus obtaining a mixture of (5.29 g) 2,2,2-Cryptor-N-(5-fluoro-2-trifloromethyl)ndimethylacetamide and its isomer in the ratio of 1:4, which nitrous the same procedure as in the first stage. Nitrate (3 g) are heated at boiling temperature under reflux with morpholine (10 ml) in 1,2-dichloroethane (30 ml) for 3 h, the mixture is evaporated to remove the research. The residue was diluted with dichloromethane, washed with HCl (0,5 N., 100 ml). The organic phase is purified flash chromatography (hexane/EtOAc, 7:3 to 1:1), while receiving specified in the title compound 5-morpholine-4-yl-4-nitro-2-cryptomaterial (2,48 g), LC-MS: m/e=306,1 (M-N), 308,2 (M+H).1H-NMR (500 MHz, CDCl3): of 8.04 (s, 1H), 6.35mm (s, 1H), 4,54 (Sirs, 1H), 3,90 (m,4H), of 3.07 (t, 4H).

The solution ndimethylacetamide (210 mg) in methanol (2 ml) is treated with 40% aqueous solution of methylamine (0.5 ml) for 16 hours. After evaporation the residue is suspended in water, and filtering the suspension gives specified in title product (90 mg). FIA-MS: m/e=197,1 (M-N).

Example 34

4-Amino-N-(2-dimethylaminoethyl)-2,5-dimethoxybenzene (DC-1787-162). To a solution of 4-amino-5-chloro-2-methoxybenzoic acid (300 mg, 1,49 mmol) in CH2Cl2(8 ml) is added N,N-dimethylethylenediamine (263 mg, 2,98 mmol), EDCI (428 mg, of 2.23 mmol), hydrate NOWT (201 mg, 1,49 mmol) and diisopropylethylamine (777 μl, 4,47 mmol). The reaction mixture was stirred at room temperature is 48 hours. The reaction mixture was diluted with CH2Cl2and washed with saturated NaHCO3and a saturated solution of salt. The organic phase is dried over MgSO4, filtered and evaporated, thus obtaining a white solid (423 mg, contains small amounts of impurities).

1H-NMR (500 MHz, DMSO-d6) 8,08 (t, 1H), of 7.70 (s, 1H), 6,47 (s, 1H), 5,96 (s, 2H), 3,82 (s, 1H), 3,34 (kV, 2H), of 2.45 (t, 2H), 2,25 (C, 6N) ppm; MS (FIA) 227,1 (M+H).

Example 35

N-Cyano-N'-((4-(4-tert-butoxycarbonyl)piperazinylcarbonyl)phenyl)-O-phenylazomethine. A mixture of tert-butyl ester 4-(4-aminobenzoyl)piperazine-1-carboxylic acid (520 mg, 1.70 mmol) and diphenylcyanoarsine (406 mg, 1.70 mmol) in dimethylacetamide (3.0 ml) is heated at 150°C for 30 minutes the Mixture is concentrated and purified column chromatography on silica gel with elution with a mixture of EtOAc:hexane (from 5 to 35% EtOAc), while receiving specified in the title compound (177 mg, 23%) as a white solid.

MS (ES+): m/z=of 450.1;1H-NMR (CDCl3, 500 MHz): δ to 1.48 (s, N), 3,26-a 3.83 (m, 8H), 7,16 (d, 2H), 7,34 (t, 1H), 7,42-7,49 (m, 6N).

Example 36

A mixture of benzyl ester of 4-(4-amino-2,6-dimethoxyphenoxy)piperidine-1-carboxylic acid (57,8 mg, 0,180 mmol) and diphenylcyanoarsine (42,4 mg, 0,180 mmol) in toluene (1.0 ml) is heated at 100°With during the night. Mixture conc the shape and purified column chromatography on silica gel with elution with a mixture of EtOAc:hexane (from 40 to 60% EtOAc), while receiving specified in the header connection (65,3 mg, 82%) as a colourless oil. MS (ES+): m/z=531,2.

Example 37

N-Cyano-N'-(4-morpholinomethyl)-O-phenylazomethine. To 4-morpholinothio (196 g, <1.10 mol) in isopropanol (2 l) is added over 0.5 hour diphenylcyanoarsine (250 g, 1.05 mol) and the mixture is stirred for 22 hours. The solid is filtered off, washed with isopropanol to obtain colorless wash liquid, and then suspended in MTBE and again filtered. The connection is dried, thus obtaining N-cyano-N'-(4-morpholinomethyl)-O-phenylazomethine (319 g, yield 95%) as not quite white solid.

1H-NMR (DMSO-d6, 500 MHz) of 10.6 (s, 1H), 7,43 (t, 2H), 7,29 (m, 5H), to 6.95 (d, 2H), to 3.73 (m, 4H), 3,10 (m, 4H) ppm; MS (FIA) 323,2 (M+H); HPLC (method A) 3,126 minutes

Similarly receive the following connections:

ArMS (M+N)Retention time (HPLC method)1H NMR

500 MHz

(solvent)
357,13,360 (A)(500 MHz, DMSO-d6) of 10.6 (s, 1H), 7,43 (m, 2H), 7,35 (d, 1H), 7,29 (m, 2H), 7,18 (m, 1H), was 7.08 (d, 1H), 6,95 (DD, 1H), and 3.72 (m, 4H), 3,17 (m, 4H) ppm
328,1 3,527 (A)(500 MHz, DMSO-d6) of 10.3 (s, 1H), 7,43 (m, 2H), 7,28 (m, 1H), 7,15 (m, 2H), 6,97 (s, 1H), 6,78 (s, 1H), 3,86 (s, 3H), 3,81 (s, 3H), 3,71 (s, 3H) ppm
268,13,592 (A)(500 MHz, DMSO-d6) of 10.4 (s, 1H), 7,43 (t, 2H), 7,31 (m, 3H), 7,16 (d, 2H), 7,12 (DD, 1H), 6,98 (t, 1H), 3,88 (s, 3H) ppm
362,14,047 (A)(500 MHz, DMSO-d6) to 10.8 (s, 1H), 7,45 (t, 2H), 7,31 (m, 4H), 7,18 (d, 1H), 7,02 (d, 1H), 7,00 (t, 1H), 4,60 (m, 1H), 1,29 (d, 6N) ppm
362,24,039 (A)(500 MHz, DMSO-d6) to 10.8 (s, 1H), 7,45 (t, 2H), 7,31 (m, 4H), 7,17 (d, 1H), 7,03 (DD, 1H), 7,00 (t, 1H), 4,60 (m, 1H), 1,29 (d, 6N) ppm
337,22,758 (A)(500 MHz, DMSO-d6) 7,43 (m, 4H), 7,30 (m, 5H), of 3.57 (m, 4H), 3.46 in (s, 2H), a 2.36 (m,4H) ppm
350,22,622 (A)(500 MHz, DMSO-d6) of 7.2-7.5 (m, 5H), to 6.95 (d, 2H), 6,5 (d, 2H), 2,7-2,4 (Shir. m, 8H), 2.40 a (s, 3H) ppm
321,32,843 (A)(500 MHz, DMSO-d6) 7,43 (m, 2H), 7,33 (m, 4H), 7,26 (m, 3H), 3,70 (m, 2H), 2.57 m (s, 2H), 1,73 (m, 4H) ppm
351,22,805 (A)(500 MHz, DMSO-d6) to 10.8 (s, 1H), 7,42 (m, 4H), and 7.3 (m, 5H), of 3.54 (m, 4H), to 3.35 (m, 1H), 2,37 (m, 2H), and 2.26 (m, 2H), 1.26 in (d, 3H) ppm
335,22,858 (A)(500 MHz, DMSO-d6) of 10.7 (s, 1H), 7,43 (t, 2H), 7,32 (m, 4H), 7,26 (m, 3H), 3,36 (m, 1H), has 2.56 (m, 2H), 2,39 (m, 2H), 1.69 in (m, 4H), of 1.32 (d, 3H) ppm
sauce 337,12,630 (A)(500 MHz, DMSO-d6) of 10.9 (s, 1H), 7,45 (m, 3H), 7,35 (d, 2H), 7,30 (m, 3H), 7,16 (d, 1H), 3,54 (m, 4H), 3,47 (s, 2H), 2,35 (m, 4H) ppm
411,22,987 (A)(500 MHz, DMSO-d6) of 10.7 (s, 1H), 7,44 (t, 2H), 7,28 (m, 3H), to 7.09 (s, 1H), of 6.96 (s, 2H), 3,98 (t, 2H in), 3.75 (s, 3H), of 3.56 (m, 4H), of 2.36 (m, 6N), to 1.86 (m, 2H) ppm
439,23,139 (A)(500 MHz, DMSO-d6) of 10.7 (s,1H), and 7.4 (m, 2H), and 7.3 (m, 3H), and 7.1 (s, 1H), 6,95 (s, 2H), 4,0 (m, 2H), of 3.75 (s, 3H), 3,5 (m, 2H), 2,8 (m, 2H), 2,4 (m, 2H), and 1.9 (m, 2H), 1,6 (m, 2H), 1,04 (d, 6N) ppm
397,23,092(A)(500 MHz, DMSO-d6) of 10.2 (s, 1H), and 7.4 (m, 2H), 7,27 (m, 3H), to 7.09 (s, 1H), of 6.96 (s, 2H), 4,01 (t, 2H in), 3.75 (s, 3H), and 2.79 (m, 6N), and 1.9 (m, 2H), 1,04 (t, 6N) ppm
392,23,033 (A)(500 MHz, DMSO-d6) of 10.7 (s, 1H), to 7.64 (s,1H), and 7.4 (m, 2H), and 7.3 (m, 3H), to 7.15 (m, 3H), of 6.96 (s, 2H), 4,13 (t, 2H), 3,88 (t, 2H), of 3.78 (s, 3H), of 2.51 (m, 2H) ppm
397,22,769 (A)(500 MHz, DMSO-d6) of 10.7 (s, 1H), 7,44 (t, 2H), 7,28 (m, 3H), 7,10 (d, 1H), 6,98 (m, 2H), 4,06 (t, 2H in), 3.75 (s, 3H), of 3.57 (m, 4H), 2,68 (t, 2H), 2,47 (m, 4H) ppm
383,22,867 (A)(500 MHz, DMSO-d6) of 10.6 (s, 1H), and 7.4 (m, 2H), and 7.3 (m, 3H), and 7.1 (s, 1H), 6,95 (m, 2H), a 4.03 (t, 2H), 3,78 (m, 2H), 3,76 (s, 3H), 3,85 (m, 2H), 3,65 (m, 2H), 0,99 (t, 6N) ppm
425,22,845 (A)(500 MHz, DMSO-d6) of 10.7 (s, 1H), 7,44 (t, 2H), 7,27 (m, 3H), was 7.08 (s, 1H), 6,95 (s, 2H), 3.96 points (t, 2H in), 3.75 (s, 3H), 3,55 (m, 4H), 2,31 (m, 6N), 1,71 (m, 2H), and 1.56 (m, 2H) ppm
282,13,488 (A)NMR (500 MHz, DMSO-d6) of 10.7 (s, 1H), 7,44 (t, 2H), 7,27 (m, 3H), to 7.09 (d, 1H), 6.90 to (m, 2H), 6,04 (s, 2H) ppm
422,4(CDCl3): δ for 1.49 (s, N), 3,13-3,19 (m, 4H), 3,56-to 3.64 (m, 4H), 6,94 (d, 2H), 7,13 (d, 2H), 7.24 to 7,33 (m, 3H), 7,39-7,44 (m, 2H)
362,2(CDCl3): δ 0,39-of 0.54 (m, 4H), 1,61-1,72 (m, 1H), 2.71 to and 2.83 (m, 4H), 3,13-up 3.22 (m, 4H), 6.90 to (d, 2H), 7,12 (d, 2H), 7,20-7,33 (m, 3H), 7,37-7,44 (m, 2H)
to 351.3(CDCl3): δ of 1.28 (d, 6N), 2,42-of 2.50 (m, 2H), 3.43 points-to 3.49 (m, 2H), of 3.77-a 3.87 (m, 2 is), 6,93 (d, 2H), 7,14 (d, 2H), 7.24 to 7,34 (m, 3H), 7,39-7,46 (m, 2H)
297,2(CD3SOCD3): δ 3,01-3,13 (m, 2H), 3,48-of 3.60 (m, 2H), 4,59-4,70 (m,1H), 5,54-5,67 (m, 1H), to 6.57 (d, 2H), 7,05-rate of 7.54 (m, 7H), of 10.4 (s, 1H)
380,21,77

Example 38

N-Cyano-N'-(2,4-acid)-O-phenylazomethine. To a suspension of diphenylcarbonate (3.0 g, 12,59 mmol) in isopropanol (15 ml) is added 2,4-dimethoxyaniline (2,02 g, 13,22 mmol). The reaction mixture was stirred at room temperature for 24-48 hours. The solid is separated by filtration, washed with isopropanol and dried in vacuum, obtaining mentioned in the title compound as a brown solid (3.55 g, yield 95%).

1H-NMR (500 MHz, DMSO-d6) or 10.60 (Sirs, 1H), 7,52-7,40 (m, 3H), 7,35-7,07 (m, 3H), 7,00 (d,d, 1H), 6,85 (DD, 1H), 3,81 (s, 3H) ppm; LC-MS 289,12 (M+H); HPLC (method A) 3,32 minutes

Similarly receive the following connections:

ArMS (M+N)Retention time (HPLC method)1H NMR

500 MHz

(solvent)
286,133,36DMSO d6: or 10.60 (Sirs, 1H), 7,52-7,40 (m,3H), 7,35-7,07 (m, 3H), 7,00 (d,d, 1H), 6,85 (DD, 1H) 3,81 (c, 3H)
289,123,32DMSO d6:10,28 (c, 1H), 7,51-7,38 (m, 2H), 7,35-7,05 (m, 4H), 6,69 (c, 1H), of 6.52 (d, 1H), 3,88 (c, 3H), 3,80 (c, 3H)
282,133,34DMSO d6:10,35 (Sirs, 1H), 7,55? 7.04 baby mortality (m, 6H), 6,86 (c, 1H), 6,85 to 6.75 (m, 1H)
298,13,3DMSO d6: 10,47 (c, 1H), 7,43 (t, 2H), 7,28 (m, 2H), 7,19 (d, 2H), 7,15-7,03 (m,2H), 6,97 (d,d, 1H), 3,83 (c, 3H), 3,80 (c, 3H)
323,21,94DMSO d6: of 10.21-9,95 (m, 1H), 7,55-to 6.95 (m, 6H), 6,57-to 6.43 (m, 2H), 3,39-up 3.22 (m, 4H), 2,31-of 2.09 (m, 3H), 1,12-to 0.97 (m, 6H)
252,153,33DMSO d6: 10,49 (c, 1H), EUR 7.57-7,07 (m, 8H), 2,32 (c, 3H)
292,163,88DMSO d6: 10,35 (c, 1H), 7,58 was 7.45 (m, 2H), 7,32-7,01 (m, 6H), 2,81-of 2.64 (m, 4H), 1.85 to of 1.62 (m, 4H)
353,13,06DMSO d6: 10,16 (c, 1H), 7,51 was 7.45 (m, 2H), 7,27 (t, 1H), 7,19-7,01 (m, 3H), 7,63 (d, 1H), 6,5 (d, 1H), 3,88 (c, 3H), 3,79-3,61 (m, 4H)
271,983,42 DMSO d6: 10,89 (c, 1H), 7,65-7,51 (m, 2H), 7,49 and 7.36 (m, 4H), 7,35-7,16 (m, 3H)
298,123,32DMSO d6: 10,45 (c, 1H), 7,43 (t, 2H), 7,18 (t, 1H), 7,03 (d, 2H),? 7.04 baby mortality (d, 1H), 6,95 (d, 1H), 6.89 in (DD, 1H), 3,82 (c, 3H), 3.72 points (c, 3H)
302,063,49DMSO d6: 10,88 (c, 1H), of 7.48 (d, 1H), 7,44 (t, 1H), 7,30 (m, 1H), 7,30-7,17 (m, 3H), 6,98 (DD, 1H), 3,78 (c, 3H);
364,0 (M-N)the 3.8DMSO d6: 10,35 (c, 1H), to 7.59 (c, 1H), 7,52-7,40 (m, 2H), 7,35-7,06 (m, 3H), 6,93 (c, 1H), was 4.02 (c, 3H), 3,95 (c, 3H)
383,23,0DMSO d6: accounted for 10.39 (c, 1H), 7,42 (t,2H), 7,27 (t,1H), 7,15 (Sirs, 2H), of 6.96 (c, 1H), 6,63 (c, 1H), 3,85 (c, 3H), a 3.87-3,63 (m, 7H), 3,09-2,90 (m, 4H)
427,251,85DMSO d6: 10,29 (c, 1H), 7,46-7,40 (m, 2H), 7,27 (t, 1H), 7,15 (Sirs, 2H), 6,97 (c, 1H), 6,80 (c, 1H), 4,13 (t, 2H), 3,85 (c, 3H), 3,71 (c,3H), of 3.57 (t, 4H), 2,69 (t, 2H), 2,53-to 2.42 (m, 4H)
278,2to 3.73DMSO d6: 10,55 (c, 1H), 7,49-7,35 (m, 2H), 7,33-7,02 (m, 6H), 2,99-2,82 (m, 4H)
318,13,78DMSO d6: 11,23 (c, 1H), 7,51-7,13 (m, 8H)

Example 39

N-Cyano-1-[4-(2-DIMET is aminoethylamino)-2,5-acid]-2-phenylazomethine. To a solution of the hydrochloride of N-(2-dimethylaminoethyl)-2,5-dimethoxybenzene-1,4-diamine (0.05 g, 0,143 mmol) in distilled water (1 ml) is added To a2CO3(0,065 g, 0.47 mmol). The mixture is diluted with EtOAc (1 ml) and add diphenylcyanoarsine (0,032 g, 0,136 mmol). The reaction mixture was stirred at room temperature for 18 hours. The precipitate was separated by filtration and washed with a minimum amount of EtOAc, while receiving specified in the title compound as a light red solid (0.015 g, yield 29%).

1H-NMR (500 MHz, DMSO-d6) 10,11 (s, 1H), 7,51-7,33 (m, 2H), 7,31-6,98 (m, 3H), for 6.81-only 6.64 (m, 1H), 6,28 (Sirs, 1H), 4,87 (Sirs, 1H), 3,85-3,62 (m, 5H), of 3.12 (s, 3H), 2,17 (C, 6N) ppm; LC-MS 384,3 (M+H); HPLC to 1.9 min (method A).

384,31,9DMSO d6: 10,11 (s, 1H), 7,51-7,33 (m, 2H), 7,31-6,98 (m, 3H), for 6.81-only 6.64 (m, 1H), 6,28 (Sirs, 1H), 4,87 (Sirs, 1H), 3,85-3,62 (m, 5H), of 3.12 (s, 3H), 2,17 (C, 6N)

Example 40

N-Cyano-1-[3,5-dimethoxy-4-(2-morpholine-4-ylethoxy)phenyl]-2-phenylazomethine. A solution of 3,5-dimethoxy-4-(2-morpholine-4-ylethoxy)phenylamine (of 0.62 mmol) in isopropanol (5 ml) and triethylamine (0.25 ml, to 1.79 mmol) was stirred at room temperature for 10 minutes Add the solution diphenylcyanoarsine (163 mg, of 0.68 mmol) in isopropanol (1 ml) and the reactions is nnow the mixture is heated at 60° C for 3 hours. The solvent is evaporated and the residue purified column chromatography with elution from 2% to 5% Meon in CH2Cl2while this is mentioned in the title compound as a yellow solid (0,275 g, yield quantitative).

1H-NMR (500 MHz, DMSO-d6) 10,9-10,49 (width, 1H), 7,45 (t, 2H), 7,35-7,25 (m, 3H), USD 5.76 (s, 2H), 4,0-of 3.94 (m, 2H), 3,76 (C, 6N), 3,68-3,50 (Shir. s, 4H), 2,80 to 2.35 (m, 6N) ppm; LC-MS 427,18 (M+H); HPLC 1,78 minutes

ArMS (M+N)Retention time (HPLC method)1H NMR

500 MHz

(solvent)
427,181,78DMSO-d6: 10,9-10,49 (width, 1H), 7,45 (t, 2H), 7,35-7,25 (m, 3H), USD 5.76 (s, 2H), 4,0-of 3.94 (m, 2H), 3,76 (C, 6N), 3,68-3,50 (Shir. s, 4H), 2,80 to 2.35 (m, 6N)

Example 41

N-Cyano-N'-(3,4,5-trimethoxyphenyl)-O-phenylazomethine. A mixture of 3,4,5-trimethoxyaniline (1,83 g, 10 mmol) and diphenylcarbonate (2,62 g, 11 mmol) in isopropanol (30 ml) was stirred at 100-110°C for 1 hour. The reaction mixture is cooled and filtered while washing with ether, thus obtaining specified in the header connection (2,79 g, yield 85%) as a white solid.

1H-NMR (500 MHz, DMSO-d6) to 10.8 (s, 1H), 7,45 (t, 2H), 7,31 (m, 3H), 6,83 (s, 2H), 3,76 (C, 6N), the 3.65 (s, 3H) ppm; MS (FIA) 328 (M+H); HPLC (method A) 3,211 minutes

Similarly receive the following connections:

263,2td align="left">  
ArMS (M+N)Retention time (HPLC method)1H NMR

500 MHz

(solvent)
298,13,185 (A)NMR (500 MHZ, DMSO-d6) 10,7 (c, 1H), 7,44 (t, 2H), 7,28 (m, 3H), 7,10 (c, 1H), 6,97 (m, 2H), 3.75 to (c, 6H) ppm
274,13,638 (A)NMR (500 MHz, DMSO-d6) 10,7 (c, 1H), 7,6 (m, 1H), and 7.4 (m, 3H), 7,31 (m, 1H), 7,15 (m,3H) ppm
309,12,654 (A)NMR (500 MHz, DMSO-d6) 10,5 (c, 1H), 7,43 (m, 2H), 7,28 (m, 1H), 7,21 (m, 4H), only 6.64 (d, 2H), 3,32 (kV, 4H), of 1.07 (t, 6H) ppm
280,13,268 (A)NMR (500 MHz, DMSO-d6) 11,2 (c, 1H), to 7.99 (DD, 2H), a 7.62 (d, 2H), 7,46 (t, 2H), 7,35 (m, 3H), 2.57 m (c, 3H) ppm
342,13,629 (A)NMR (500 MHz, DMSO-d6) 11,2 (c, 1H), 7,80 (d, 2H), 7,73 (m, 2H), to 7.67 (m, 3H), EUR 7.57 (t, 2H), 7,47 (t, 2H), 7,35 (m, 3H) ppm
280,13,184 (A)NMR (500 MHz, DMSO-d6) 11,0 (c, 1H), 8,04 (d, 2H), to 7.84 (d, 1H), 7,76 (DD, 2H), EUR 7.57 (t, 1H), 7,46 (t, 2H), 7,31 (m, 3H), 2,59 (c, 3H) ppm
441,23,017 (A)NMR (500 MHz, DMSO-d6) 10,8 (c, 1H), 7,46 (m, 2H), was 7.36 (d, 1H), 7,30 (d, 1H), 7,15 (m, 3H), 6,85 (c, 1H), 4,0 (m, 2H), 3,91 (m, 2H), 3,76 (c, 6H), 3,66 (t, 2H), 3,48 (m, 2H), 3,35 (m, 2H), 3,1 (m, 2H), a 2.01 (m, 2H) ppm
469,23,194 (A)NMR (500 MHz, DMSO-d6) 10,8 (c, 1H), 7,46 (m, 2H), was 7.36 (d, 1H), 7,30 (d, 1H), 7,15 (t, 3H), 6,85 (c, 1H), 3,91 (m, 2H), 3,83 (m, 2H), 3,78 (c, 6H), 3,50 (d, 2H), and 3.31 (m, 2H), to 2.67 (m, 2H), 2,01 (m, 2H), to 1.15 (d, 6H) ppm
397,33,037 (A)NMR (500 MHz, DMSO-d6) 7,44 (t, 2H), 7,28 (m, 3H), 7,10 (c, 1H), 6,95 (c, 2H), 4,0 (t, 2H), 3.75 to (c, 6H), 3,18 (c, 2H), 2,85 (m, 4H), of 1.95 (m, 2H), 1,10 (t, 6H) ppm
454,22,885 (A)NMR (500 MHz, DMSO-d6) 10,8 (c, 1H), and 7.4 (m, 2H), and 7.3 (m, 2H), 7,30 (d, 1H), 7,15 (m, 3H), 6,7 (c, 2H), 3,9 (m, 2H), of 3.77 (c, 6H), of 3.75 (m, 2H), 3,3 (m, 4H), 2,85 (c, 3H), of 1.97 (m, 2H) ppm
to 455.23,095 (A)NMR (500 MHz, DMSO-d6) 10,8 (c, 1H), 7,46 (m, 2H), was 7.36 (d, 1H), 7,30 (d, 1H), 7,15 (m, 3H), 6,85 (c, 1H), 4,0 (m, 2H), 3,9 (m, 2H), of 3.77 (c, 6H), and 3.6 (t, 2H), 3.45 points (d, 2H), 3.15 in (m, 2H), 3,05 (m, 2H), of 1.85 (m, 2H), 1,65 (m, 2H) ppm
441,23,205 (A)NMR (500 MHz, DMSO-d6) 10,8 (c, 1H), 7,46 (m, 2H), was 7.36 (d, 1H), 7,30 (d, 1H), 7,15 (who, 3H), 6,85 (c, 1H), 3,9 (m, 2H), 3,74 (c, 6H), 3,1 (m, 10H), and 1.8 (m, 2H), 1,65 (m, 2H), 1,2 (t, 6H) ppm
295,12,54DMSO d6: 10,76 (c, 1H), there is a 10.03 (c, 1H), 7,58 (d, 2H), 7,46-7,40 (m, 4H), 7,31-7,25 (m, 3H), 2,04 (c, 3H)
244,2
204,2
246,2
252,2
298,2
296,1
344,2
330,2
282,0
281,2
268,2
328,02,01
309,11,9
321,12,1
296,03,7
282,03,2
296,03,2
282,03,6
278,02,6
321,02,9
282,03,5
323,03,0
272,13,38
282,13,60
268,14,03
290,1of 3.64
280,14,03
286,1to 3.73
270,13,51
286,13,68
328,14,16
286,13,42
274,13,34
256,13,25
268,2
326,2
312,2
316,1
332,1
338,24,63
298,03,39
409,22,07
327,83,28
409,22,03
to 326.13,94
381,171,88
409,222,10
466,34
img src="https://img.russianpatents.com/883/8838302-s.jpg" height="25" width="30" > 522,32,47
392,321,90
394,211,76
422,35to 2.06
420,26
427,212,11
422,222,04
353,233,19
312,043,33
427,262,09
296,1
282,0
268,13,45 (A)DMSO(d6): 10,84 (c, 1H), 7,45 (t, H), 7,30 (m, 4H), 7,06 (m, 2H), PC 6.82 (DD, 1H)
268,13,38 (A)DMSO(d6): 10,67 (c, 1H), 7,43 (t, 2H), 7,37 (d, 2H), 7,26 (d, 2H), 7,28 (m, 1H), of 6.96 (d, 2H)
296,13,40 (A)DMSO(d6): 11,17 (c, 1H), 7,98 (d, 2H), to 7.64 (d, 2H), 7,46 (t, 2H), 7,34 (d, 2H), 7,31 (m, 1H), 3,84 (c, 3H)
281,12,77 (A)DMSO(d6): 10,95 (c, 1H), 8,03 (c, 1H), 7,95 (c, 1H), 7,74 (d, 1H), 7.62mm (d, 1H), 7,46 (m, 4H), 7,30 (m, 3H)
317,02,80 (A)DMSO(d6): 11,04 (c, 1H), 7,95 (c, 1H), 7,69 (TD, 2H), 7,60 (t, 1H), 7,45 (m, 4H), 7,31 (m, 3H)
317,02,83 (A)DMSO(d6): 11,08 (c, 1H), 7,82 (d, 2H), 7,63 (d, 2H), 7,45 (t, 2H), 7,33 (d, 2H), and 3.31 (d, 2H), 7,30 (m, 1H)
295,12,94 (A)DMSO(d6): 10,85 (c, 1H), 10,01 (c, 1H), 7,80 (c, 1H), 7,45 (t, 2H), 7,38 (d, 1H), 7,27 (m, 4H), 7,13 (d, 1H), 2,04 (c, 3H)
342,13,19 (A)DMSO(d6): 10,63 (c, 1H), 7,44 (t, 2H), 7,29 (d, 1H), 7,26 (d, 2H), 7,10 (c, 1H), 6,95 (c, 2H), 4,06 (m, 2H), 3.75 to (c, 3H), of 3.64 (m, 2H), 3,30 (c, 3H)
342,13,20 (A)DMSO(d6): to 10.62 (c, 1H), 7,43(t, 2H), 7,29 (d, 1H), 7,25 (d, 2H), 7,10 (d, 1H), 6,97 (m, 2H), 4,06 (DD, 2H), 3.75 to (c, 3H), 3,66 (DD, 2H), 3,29 (c, 3H)
386,23,21 (A)DMSO(d6): or 10.60 (c, 1H), 7,44 (t, 2H), 7,29 (d, 1H), 7,26 (d, 2H), 7,11 (d, 1H), 6,97 (m, 2H), 4,08 (m, 4H), to 3.64 (DD, 4H), 3,29 (c, 3H), 3,31 (c, 3H), 3,30 (c, 3H)
238,2of 3.27 (A)DMSO(d6): 10,82 (c, 1H), 7,45 (m, 6H), of 7.23 (m, 4H)
298,13,39 (A)DMSO(d6): 10,77 (c, 1H), 7,44 (t, 2H), 7,29 (d, 2H), of 6.68 (d, 2H), to 6.39 (t, 1H), of 3.73 (c, 6H)
306,13,61 (A)DC0(d6): br11.01 (c, 1H), 7,86 (c, 1H), 7,79 (d, 1H), 7,65 (t, 1H), 7,60 (d, 1H), 7,46 (m, 2H), 7,35 (m, 3H)
310,13,86 (A)DMSO(d6): to 10.62 (c, 1H), 7,43 (t, 2H), 7,33 (d, 2H), 7,27 (t, 1H), 7,24 (d, 2H), 6,93 (d, 2H), 3,95 (t, 2H), by 1.68 (m, 2H), 1,42 (m, 2H), to 0.92 (t, 3H)
274,13,59 (A)DMSO(d6): 10,91 (c, 1H), 7.62mm (DDD, 1H), 7,49 (t, 1H), 7,45 (t, 2H), 7,31 (m, 4H)
332,03,63 (A)DMSO(d6): 10,50 (c, 1H), 7,43 (t, 2H), 7,28 (m, 1H), 7,22 (d, 2H), 7,17 (d, 2H), 3,84 (c, 3H), 3,81 (c, 3H)
302,1of 3.60 (A)
to 326.13,32 (A)
336,13,71 (A)
328,13,55 (A)DMSO(d6): 8,70 (c, 1H), 7,55 (t, 1H), 7,45 (m, 1H), 7,40 (t, 1H), 6,92 (c, 2H), 6,34 (c, 2H), 3,69 (c, 6H), 3,56 (c, 3H)
274,13,52 (A)DMSO(d6): 10,92 (c, 1H), 7,45 (m, 4H), 7,30 (m, 1H), 7.23 percent (m, 3H)
352,14,11 (A)
322,13,75 (A)
326,24,00 (A)
452,24,08 (A)DMSO(d6): 11,30 (c, 1H), 8,07 (c, 1H), 7,55 (c, 1H), 7,46 (t, 2H), 7,30 (m, 1H), 7,18 (d, 2H), 3,70 (t, 4H), to 3.02 (t, 4H)
341,23,50 (A)
354,24,30 (A)DMSO(d6): 10,69 (c, 1H), 7,44 (t, 2H), 7,29 (d, 1H), 7,28 (d, 2H), 6,61 (c, 2H), 6.30-in (t, 1H), 4,55 (m, 2H), 1,24 (d, 12H)
352,22,35
312,23,88 (A)
353,3to 3.02 (A)DMSO(d6): 10,66 (c, 1H), 7,44 (t, 2H), 7,29 (d, 1H), 7,26 (d, 2H), was 7.08 (d, 1H), 6,98 (DD, 1H), to 6.88 (d, 1H), of 3.77 (c, 3H), 3,70 (t, 4H), to 2.94 (t, 4H)
381,33,09
395,31,96DMSO(d6): of 10.73 (c, 1H), 7,44 (t, 2H), 7,28 (m, 4H), 7,11 (c, 1H), 6,98 (d, 1H), 4,55 (m, 1H), 3,55 (m, 4H), 3,41(c, 2H), is 2.37 (m, 4H), of 1.27 (d, 6H)
335,31,82
348,3with 3.27DMSO(d6): 10,81 (c, 1H), 7,82 (c, 1H), 7,68 (DD, 1H), 7,44 (t, 2H), 7,30 (m, 3H), 7,21 (d, 1H, in), 3.75 (t, 4H), 3,14 (t, 4H)

Below are examples of methods used in obtaining diaminetetra. The examples also serve to describe several methods of cleaning. Data for these compounds are contained in the table below.

Example 42

Method And

N3-(2-Chloro-4-morpholine-4-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine. A mixture of N-cyano-N'-(2-chloro-4-Mor is olivenol)-O-phenylazomethine (0.10 g, 0.28 mol) and 2-hydrazinopyridazine (0,046 g, 0.42 mmol) in isopropanol (3 ml) is heated at 115°C for 20 hours. The precipitate is filtered off, washed with isopropanol and purified flash chromatography (SiO2) with elution with a mixture of 2:98 methanol:dichloromethane, while receiving specified in the header connection (0,080 g, yield 79%) as a white solid.

Example 43

Method And*

N3-(2,4-Acid)-1-(2-forfinal)-1H-[1,2,4]triazole-3,5-diamine. A mixture of N-cyano-N'-(2,4-acid)-O-phenylazomethine (0.10 g, 0.34 mmol), hydrochloride of 2-forfamilies (0.08 g, 0.50 mmol) and triethylamine (0.01 ml, of 0.68 mmol) in isopropanol (3 ml) is heated at 100°C for 18 h and evaporated. Purification with flash chromatography (SiO2) with elution with a mixture of 1:1 ethyl acetate:hexane network specified in the title compound (0.10 g, yield 85%).

Example 44

The way A**

4-[5-Amino-3-(3,4-dimethoxyaniline)[1,2,4]triazole-1-yl]benzonitrile. To N-cyano-N'-(3,4-acid)-O-phenylazomethine (0,215 g, 0,723 mmol) in isopropanol (3 ml) is added 0,184 g (1.5 equivalent) of the hydrochloride of 4-hydrazinobenzothiazole then adding 152 μl (1.5 equivalents) of triethylamine and a catalytic amount (0.2 equivalent) of 4-dimethylaminopyridine. The reaction mixture is stirred for Naciri 100 degrees Celsius. The reaction mixture is concentrated to dryness and purified column chromatography with reversed phase. The pure fractions are dried, thus obtaining 4-[5-amino-3-(3,4-dimethoxyaniline)[1,2,4]triazole-1-yl]benzonitrile in the form of a reddish-brown solid (18.3 mg, yield of 7.5%).

Method In

N3-[4-(4-Methylpiperazin-1-ylmethyl)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine. A mixture of N-cyano-N'-(4-(4-methyl)piperazinylmethyl)-O-phenylazomethine (0,60 g, 1,72 mmol) and 2-hydrazinopyridazine (0,23 g of 2.06 mmol) in isopropanol (8 ml) are heated in a microwave oven (Emrys) at 180°C for 10 min, then evaporated. Purification with flash chromatography (SiO2) with elution with a mixture of 0.2:2:98 NH4OH:methanol:dichloromethane gives specified in the title compound (0.54 g, yield 87%) as a pale tan solid.

Example 45

Way

1-(2-fluoro-4-itfeel)-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine. A mixture of N-cyano-N'-(4-morpholinomethyl)-O-phenylazomethine (0,69 g, 2.14 mmol) and 2-fluoro-4-jdpennington (0.65 g, 2.57 mmol) in dimethylacetamide (4 ml) is heated at 120°C for 24 hours. The reaction mixture was diluted with ethyl acetate, washed with water (3 times) and saturated salt solution, dried (sodium sulfate) and evaporated. Purification with flash chromatography (SiO2) with elution with a mixture of 4:96 meta is ol:dichloromethane followed prepreparation HPLC receive specified in the title compound (0.03 g, yield 5%) as a white lyophilisate.

Example 46

The method*

N3-[4-(3-Diethylaminopropyl)for 3,5-acid]-1-(2-forfinal)-1H-[1,2,4]triazole-3,5-diamine. A solution of the hydrochloride of 2-forfamilies (0.15 g, of 0.91 mmol) and triethylamine (0,13 ml of 0.91 mmol) in dimethylacetamide (1 ml) is stirred for 0.5 hour at room temperature. Add N-cyano-N'-(4-(3-diethylaminopropyl)for 3,5-acid)-O-phenylazomethine (0,30 g in a mixture with the salt of triethylamine and triperoxonane acid, 0.45 mmol) in dimethylacetamide (1 ml) and the reaction mixture stirred at 120°C for 20 hours. The precipitate is removed and the filtrate is washed with ether. The remaining aqueous phase is evaporated and purified prepreparation HPLC, while receiving specified in the title compound (0.01 g, yield 4%) as a white lyophilisate.

Example 47

Method D

N-(4-Deformedarse-3-isopropoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine. A mixture of N-cyano-N'-(deformedarse-3-isopropoxyphenyl)-O-phenylazomethine (0.10 g, 0.28 mmol) and 2-hydrazinopyridazine (0.06 g, 0,56 mmol) in dimethylacetamide (3 ml) is heated in a microwave apparatus at 220°C for 15 minutes the Reaction mixture is cooled, poured into a mixture of ice-water and stirred for 0.5 hour. The precipitate was separated by filtration, washed with cold water and dry the t, while receiving specified in the title compound (0.10 g, yield 97%) as a light pink solid.

Example 48

The way D*

4-[5-Amino-3-(4-deformedarse-3-isopropoxyaniline)-[1,2,4]triazole-1-yl]benzonitrile. A mixture of N-cyano-N'-(3-deformedarse-4-isopropoxyphenyl)-O-phenylazomethine (0.10 g, 0.28 mmol), 4-cyanopyridine (0.09 g, 0.55 mmol) and triethylamine (of 0.08 ml, 0.55 mmol) in dimethylacetamide (3 ml) is heated in a microwave apparatus at 220°within 5 minutes the Cooled reaction mixture is poured into a mixture of ice-water and the crude product is produce by filtration. Cleaning prepreparation HPLC gives specified in the title compound (0.07 g, 51%yield) as a light orange solid.

Example 49

Method E

1-(4-Utiltity-2-yl)-N3-(2-methoxy-4-morpholine-4-ylphenyl-1H-[1,2,4]triazole-3,5-diamine. A mixture of N-cyano-N'-(2-methoxyphenyl)-O-phenylazomethine (0.10 g, 0.28 mmol), (4-utiltity-2-yl)hydrazine (to 0.060 g of 0.56 mmol) and DMAP (few crystals) in dimethylacetamide (3 ml) is heated in a microwave apparatus at 220°C for 7 minutes Cleaning prepreparation HPLC gives specified in the title compound (0.01 g, yield 8%).

Example 50

Method G

1-[2-(4-Methylpiperazin-1-yl)pyrimidine-4-yl]-N3-(-morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine. A mixture of N-cyano-N'-(4-morpholinomethyl)-O-phenylazomethine (0.10 g, 0.31 mmol) and [2-(4-methylpiperazin-1-yl)pyrimidine-4-yl]hydrazine (0.08 g, 0.34 mmol) in N-methylpyrrolidinone (3 ml) is heated in a microwave apparatus at 220°C for 5 minutes Cleaning prepreparation HPLC gives specified in the title compound (0.09 g, yield 2%).

Example 51

The way G*

1-(6-Chloropyrimidine-4-yl)-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine. A mixture of N-cyano-N'-(4-morpholinomethyl)-O-phenylazomethine (8,76 g of 27.2 mmol, 4-chloro-6-hydrazinopyridazine (4.12 g, 28.5 mmol) and diisopropylethylamine (18,9 ml, 109 mmol) in N-methylpyrrolidinone (50 ml) is heated in a microwave apparatus at 220°C for 5 min, cooled down, poured into a mixture of ice-water, stirred for 0.5 hours, filtered to obtain a crude product (of 9.30 g). Purification with flash chromatography (SiO2) with elution with a mixture of 2:98 methanol:dichloromethane gives specified in the header connection (3,91 g, yield 39%) as a yellow powder.

Example 52

Way N

4-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-N-(2-morpholine-4-retil)benzamide. To 4-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)benzoic acid (4,635 g 15,643 mmol) in tetrahydrofuran (50 ml) add (7,12 g, 1.2 equivalent) of HBTU and then adding 2-morpholine-4-ylethylamine (2.24 g, 1 equivalent) and triethylamine (of 5.45 ml, 2.5 equivalent). The reaction mixture was stirred over night at room temperature. The solid is filtered off, washed with tetrahydrofuran, cold ethanol, water, ethanol and finally with ether. The connection is dried, thus obtaining 4-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-N-(2-morpholine-4-retil)benzamide (1,17 g, yield 18%) as a white solid. The organic phase contained the product, which is not further identified.

Cleanup procedures:

1. Deposition of solvent

2. Silica gel

3. Prepreparation HPLC

Retention time was determined by LC-MS, unless otherwise specified.

NameProcedure cyclizationCleaning procedureMS

(M+N)
Retention time (min)NMR
N3-(3,4-Acid)-1-(2-piperidine-1-Yeremey-4-yl)-1H-[1,2,4]triazole-3,5-diamineAnd3397,202,90(500 MHz, DMSO-d6) 8,98 (s, 1H),8,35 (d, 1H), 7,63 (s, 2H), was 7.36 (d, 1H), 7,10 (DD, 1H), 6,86 (d, 1H), 6,80 (d, 1H), 3,76 (s, 3H), of 3.69 (s, 5H), of 1.64 (2H), 1.57 in (m, 4H) ppm
N3-Benzo[1,3]dioxol-5-yl-1-(2-piperidine-1-Yeremey-4-yl)-1H-[1,2,4]triazole-3,5-diamineAnd3381,103,20(500 MHz, DMSO-d6) 9,07 (s, 1H), at 8.36 (d, 1), 7,63 (s, 2H), 7,29 (d, 1H),? 7.04 baby mortality (m, 1H), 6,80 (m, 2H), 5,94 (s,2H), 3,69 (SIRM, 4H), 1,65, (m,2H), 1.57 in (m, 4H) ppm
N3-Benzo[1,3]dioxol-5-yl-1-(4-piperidine-1-Yeremey-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd3381,102,30(500 MHz, DMSO-d6) 9,19 (s, 1H), 8,10 (d, 1H), to 7.67 (Shir. s, 2H), 7,47 (d, 1H), 7,03 (m, 1H), 6,80 (m, 2H), 5,95 (s, 2H), 3,76 (Shir. m, 4H), by 1.68 (m, 2H), 1,62 (m, 4H) ppm
N3-(4-Diethylaminophenyl)-1-(2-piperidine-1-Yeremey-4-yl)-1H-[1,2,4]triazole-3,5-diamineAnd3408,202,00(500 MHz, DMSO-d6) 10,9 (Shir. s, 1H), 9,63 (Shir. s, 1H)" 8,39 (d, 1H), to 7.77 d, 2H), 7,68 (s, 1H), 7,51 (d, 2H), 6,86 (d, 2H), 3,70 (m, 4H), 3,62 (m, 2H), 3,51 (m, 2H), 1,65 (m, 2H), 1.57 in (m, 4H), and 1.00 (t, 6H) ppm
N3-(3,4-Acid)-1-(4-piperidine-1-Yeremey-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd3397,202,20(500 MHz, DMSO-d6) of 9.00 (s, 1H), of 8.09 (d, 1H), of 7.70 (s, 2H), 7,50 (s, 1H), to 7.09 (s, 1H), 6,83 (d, 1H), 6.75 in (d, 1H), 3,76 (s, 7H), of 3.69 (s, 3H), 1,67 (m, 2H), 1,60 (m, 4H) ppm
1-Benzothiazol-2-yl-N3-(4-diethylaminophenyl)-1H-[1,2,4]triazole-3,5-diamineA*3380,102,50(500 MHz, DMSO-d6) 11,0 (Shir. s, 1H), 9,88 (s, 1H), 8,07 (d, 1H), 7,88 (d, 2H), 7,76 (d, 2H), 7,52 (m, 3H), 7,38 (m, 1H), to 3.64 (m, 2H), 3,53 (m, 2H), 1,01 (t,6H) ppm
N3-Benzo[1,3]dioxol-5-yl-1-(4-phenylthiazol-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd 2,3379,104,20(500 MHz, DMSO-d6) which 9.22 (s, 1H), 8,02 (d, 2H), 7,80 (s, 1H), 7,63 (s, 2H), 7,46 (t, 2H), 7,37 (t, 1H), 7,30 (d, 1H), 6,98 (DD, 1H), 8,84 (d, 1H), 5,95 (s, 2H) ppm
N3-(4-Diethylaminophenyl)-1-(4-phenylthiazol-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd3406,102,70(500 MHz, DMSO-d6) 11,2 (Shir. s, 1H), 10,2 (Shir. s, 1H), 7,8-8,0 (m, 5H), 7,65 (Shir. m, 1H), 7,52 (m, 2H) 7,41 (m, 1H), 6,10 (m, 2H), 3,55 (Shir. m, 4H), of 1.03 (m,6H) ppm
N3-(4-Diethylaminophenyl)-1-(4-piperidine-1-Yeremey-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd3408,201,60(500 MHz, DMSO-d6) 11,1 (Shir. s, 1H), 9,63 (Shir. s, 1H), 8,14 (d, 1H), 7,82 (d, 2H), 7,73 (s, 1H), of 7.48 (s, 2H), 6,77 (d, 1H), to 3.73 (m, 4H), 3,62 (m, 2H), 3,51 (m, 2H), by 1.68 (m, 2H), 1,60 (m, 4H), and 1.00 (t, 6N) ppm
6-[5-Amino-3-(4-diethylaminobenzylidene)[1,2,4]triazole-1-yl]nicotinamideAnd2,3349,201,90(500 MHz, DMSO-d6) 11,0 (Shir. s, 1H), 9,73 (Shir. s, 1H), 8,86 (s, 1H), 8,42 (d, 1H), to $ 7.91 (s, 1H), 7,82 (m, 3H), 7,52 (d, 2H), 3,63 (Shir. m, 2H), 3,52 (Shir. m, 2H), and 1.00 (t, 6H) ppm
N3-(3,4-Acid)-1-(4-phenylthiazol-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd2,3395,204,00(DMSO-d6, 500 MHz) becomes 9.97 (s, 1H), 8,00 (d, 2H), 7,82 (s, 1H), 7,51 (t, 2H), 7,39 (m, 2H), 7,21 (DD, 1H), 6,99 (d, 1H), 3,83 (s, 3H), 3,76 (s, 3H) ppm
N3-(3,4-Acid)-1H-[12,4]triazole-3,5-diamine And3(DMSO-d6, 500 MHz) 12,5 (Shir. s, 1H), 9,3 (Shir. s, 1H), 7.5 (a Shir. s, 2H), was 7.08 (d, 1H), 6,94 (DD, 1H), 6.89 in (d, 1H), of 3.73 (s, 3H), 3,70 (s, 3H) ppm
1-(2-Forfinal)-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineA*2355,001,60(DMSO-d6, 500 MHz) 8,56 (s, 1H), 7,4-of 7.55 (m, 2H), 7,38 (d, 2H), 7,33 (t, 1H), for 6.81 (d, 2H), 6,28 (s, 2H), 3,71 (m, 4H), 2.95 and (m, 4H) ppm
1-[4-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)phenyl]alanonAnd2295,202,90(DMSO-d6, 500 MHz) 9,73 (s, 1H), 8,43 (m, 1H), 8,01 (m, 1H), 7,89 (d, 2H), to 7.75 (m, 2H), 7,71 (d, 2H), 7,24 (m, 1H), 2,50 (s, 3H) ppm
N3-(2,4-Acid)-1-(2-forfinal)-1H-[1,2,4]triazole-3,5-diamineA*2330,102,70(DMSO-d6, 500 MHz) 7,83 (d, 1H), 7,53 (m, 1H), of 7.48 (m, 1H), 7,41 (m, 1H), 7,33 (m, 1H), 6,86 (s, 1H), return of 6.58 (d, 1H), 6,44 (DD, 1H), 6,34 (s, 2H), of 3.84 (s, 3H), 3,70 (s, 1H) ppm
[4-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-phenyl]phenylmethanoneAnd3357,103,70(DMSO-d6, 500 MHz) 9,82 (s, 1H), 8,43 (m, 1H), 7,98 (m, 1H), to 7.77 (m, 7H), of 7.69 (d, 1H), to 7.64 (t, 1H), 7,55 (t, 2H), 7,24 (m, 1H) ppm
1-(2-Forfinal)-N3-(4-(morpholine-4-ylmethylene)-1H-[1,2,4]triazole-3,5-diamineA*3(DMSO-d6, 500 MHz) 9,60 (Shir. s, 1H), 9,19 (s, 1H), 7,55 (d, 2H), 7,50 (m, 1H), 7,43 (m, 1H), 7,35(m, 1H), 7,30 (m, 2H), 6,40 (s, 2H), 4,22 (m, 2H), 3,95 (m, 2H)and 3.59 (m, 2H) 3,24 (m, 2H), is 3.08 (m, 2H) ppm
N3-(3-Morpholine-4-ylmethylene)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3(DMSO-d6, 500 MHz) to 9.91 (Shir. s, 1H), 9,38 (s, 1H), 8,43 (m, 1H), 7,99 (m, 1H), 7,72 (m, 3H), to 7.67 (s, lH), 7,37 (t, 1H), 7,24 (m, 1H), 6,98 (d, 1H), 4,33 (m, 2H), 3,98 (m, 2H), to 3.64 (m, 2H), 3,32 (m, 2H), 3,17 (m, 2H)ppm
1-(2-Forfinal)-N3-(3-morpholine-4-ylmethylene)-1H-[1,2,4]triazole-3,5-diamineA*3(DMSO-d6, 500 MHz) 9,79 (Shir. s, 1H), 9,14 (s, 1H), to 7.61 (d, 1H), 7,55 (m, 3H), 7,43 (m, lH), 7,35 (m, 1H), 7,30 (m, 1H), 6.90 to (d, 1H), 6,40 (s, 2H), 4,25 (m, 2H), 3,93 (m, 2H), 3,60 (m, 2H), 3.27 to (m, 2H), 3,13 (m, 2H) ppm
N3-(2,4-Acid)-1-(2-piperidine-1-Yeremey-4-yl)-1H-[1,2,4]triazole-3,5-diamineAnd2397,103,30(DMSO-d6, 500 MHz) at 8.36 (d, 1H), 7,95 (d, 1H), 7.62mm (s, 2H), 7,24 (s, 1H), 6,78 (d, 1H), is 6.61 (d, 1H), of 6.52 (DD, 1H), 3,84 (s, 3H), of 3.73 (s, 3H), of 3.69 (m, 4H), and 1.63 (m, 2H), and 1.56 (m, 4H) ppm
N3-(4-(Morpholine-4-ylphenyl)-1-(2-pyridine-1-Yeremey-4-yl)-1H-[1,2,4]triazole-3,5-diamineAnd3422,302,20(500 MHz, DMSO-d6) 9,20 (Shir. s, 1H), of 8.37 (d, 1H), 7,65 (s, 2H), EUR 7.57 (Shir. s, 2H), 7,10 (Shir. s, 2H), 6,83 (d, 1H), 3,81 (s, 4H), 3,70 (s, 4H), 3,18 (Shir. with 4H), of 1.64 (m, 2H), 1.57 in (m, 4H) ppm
N3-(2-Chloro-4-morpholine-4-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd2372,203,10(500 MHz, DMSO-d6) of 8.40 (m, 1H), 7,94 (m, 2H), 7,69 (s, 2H), 7.62mm (m, 2H), 7,20 (m, 1H), 7,00 (d, 1H), 6,95 (DD, 1H), of 3.73 (t, 4H), 3,06 (t, 4H) ppm
N3-[3-Methoxy-4-(3-morpholine-4-ylpropionic)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3426,201,70(500 MHz, DMSO-d6) of 9.6 (s, 1H), 8,97 (s, 1H), to 8.41 (m, 1H), 7,97 (m, 1H), to 7.67 (m, 2H), 7,43 (m, 1H), 7,43 (d, 1H), 7,20 (m, 1H), 7,12 (DD, 1H), 6,91 (d, 1H), 4.00 points (m, 2H), 3,98 (m, 2H), 3,80 (s, 3H), 3,65 (t, 2H), 3,51 (d, 1H), and 3.31 (m, 2H), 3,13 (m,
1-Pyridin-2-yl-N3-(2,4,5-trimethoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd3343,102,80(500 MHz, DMSO-d6) 8,42 (m, 1H), 8,01 (m, 1H), to 7.93 (s, 3H), 7,66 (d, 1H), 7,44 (s, 1H), 7,24 (m, 1H), 6,78 (s, 1H), 3,84 (s, 3H), 3,79 (s, 3H), 3,76 (s, 3H) ppm
N3-{4-[3-(2,6-Dimethylmorpholine-4-yl)propoxy]-3-methoxyphenyl}-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3454,202,00(500 MHz, DMSO-d6) to 9.70 (s, 1H), 8,96 (s, 1H), 8,40 (m, 1H), 7,97 (m, 1H), 7,69 (s, 1H), 7,66 (d, 1H), 7,43 (d, 1H), 7,21 (m, 1H), 7,12 (DD, 1H), 6.90 to, 3,98 (t, 2H), 3,80 (s, 5H), of 3.54 (d, 2H), 3.27 to (m, 2H), of 2.68 (m, 2H), 2,11 (m, 2H), 1.26 in (d, 6H)
1-(2-Fluoro-4-itfeel)-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine3 481,002,30(500 MHz, DMSO-d6) 8,9 (Shir. s, 1H), 7,88 (DD, 1H), 7,71 (d, 1H), 7,45 (m, 2H), 7,33 (t, 1H), 7,07 (width, 2H), 6,56 (Shir. s, 2H), 3,80 (m, 4H), 3,20 (m, 4H)
N3-[3-Methoxy-4-(4-(morpholine-4-albucosi)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3440,201,80(500 MHz, DMSO-d6) 9,60 (s, 1H), 8,93 (s, 1H), to 8.41 (DD, 1H), 7,98 (m, 1H), 7,66 (m, 2H), 7,41 (d, 1H), 7,19 (m, 1H), 7,11 (DD, 1H), to 6.88 (d, 1H), 3,99 (d, 2H), 3,93 (t, 2H), 3,79 (s, 3H), of 3.64 (t, 2H), 3.45 points (d, 2H), 3,19 (m, 2H), 3,06 (m, 2H), 1,82 (
N3-[3-Methoxy-4-(2-morpholine-4-ylethoxy)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3412,20(500 MHz, DMSO-d6) of 9.99 (s, 1H), 9,05 (s, 1H) to 8.41 (DD, 1H), 7,97 (m, 1H), to 7.67 (m, 2H), 7,47 (d, 1H), 7,21 (m, 1H), 7,13 (DD, 1H), 7,00 (d, 1H), 4,21 (d, 2H), 4.00 points (m, 2H), 3,82 (s, 3H), of 3.73 (t, 2H), 3,53 (m, 4H), up 3.22 (m, 2H), ppm
N3-[4-(2-Diethylaminoethoxy)-3-methoxyphenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3398,301,80(500 MHz, DMSO-d6) 9,34 (s, 1H), 9,03 (s, 1H), to 8.41 (DD, 1H), 7,97 (m, 1H), to 7.67 (m,2H), 7,47 (d,1H),, 7,21 (m, 1H), 7,13 (DD, 1H), 6,97 (d, 1H), 4,20 (d, 2H), 3,82 (s,3H), of 3.48 (m, 2H), 3,29 (m, 4H), of 1.25 (t, 6H) ppm
N3-[4-(3-Imidazol-1-ylpropionic)-3-methoxyphenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3407,201,90(500 MHZ, DMSO-d6) 9,16 (s, 1H), 8,96 (s, 1H), 8,40 (the d, 1H), 7,97 (t, 1H), 7,83 (s, 1H), and 7.7 (m, 3H), 7,41 (d, 1H), 7,21 (m, 1H), 7,10 (DD, 1H), to 6.88 (d, 1H), 4,39 (t, 2H), 3,92 (t, 2H), 3,79 (s, 3H), and 2.26 (m, 2H) ppm
N3-[4-(3-Diethylaminopropyl)for 3,5-acid]-1-(2-forfinal)-1H-[1,2,4]triazole-3,5-diamineS*3459,201,80(500 MHz, DMSO-d6) 9,05 (s, 1H), 8,79 (s, 1H), 7,56 (t, 1H), 7,43 (m, 2H), 7,33 (t, 1H), 6,94 (s, 2H), 6.42 per (s, 2H), 3,85 (t, 2H), 3,70 (s, 6H), of 3.28 (m, 2H), and 3.16 (m, 4H), of 1.92 (m, 2H), 1,21 (t, 6H) ppm
4-{5-Amino-3-[3,5-dimethoxy-4-(3-morpholine-4-ylpropionic)phenylamino][1,2,4]triazole-1-yl}benzonitrileS*3480,201,90(500 MHz, DMSO-d6) 9,65 (s, 1H), 9,00 (s, 1H), 7,94 (d, 2H), 7,80 (d, 2H), 7,01 (s, 2H), PC 6.82 (s, 2H), 4.00 points (d, 2H), 3,85 (t, 2H), 3,76 (s, 6H), of 3.65 (t, 2H), 3,48 (d, 2H), 3,35 (m, 2H), 3,13 (m, 2H), 1,98 (m, 2H) ppm
4-(5-Amino-3-{3,5-dimethoxy-4-[3-(4-methylpiperazin-1-yl)propoxy]phenylamino}[1,2,4]triazole-1-yl)benzonitrileS*3493,201,50(500MHz, DMSO-d6) of 9.00 (s,1H), 7,94 (d, 2H), 7,80 (d, 2H), 7,01 (s, 2H), PC 6.82 (s, 2H), 3,84 (t, 2H), 3,76 (s, 6H), was 3.7 to 2.7 (width, 13H), with 1.92 (m, 2H) ppm
4-(5-Amino-3-{4-[3-(2,6-dimethylmorpholine-4-yl)propoxy] - for 3,5-dimethoxyaniline}-[1,2,4]triazole-1-yl)benzonitrileS*3508,202,10(500 MHz, DMSO-d6) 9,77 (s, 1H), 9,01 (s, 1H), 7,95 (d, 2H), 7,80 (d, 2H), 7,01 (s, 2H), PC 6.82 (s, 2H), 3,80 (m, 4H), 3,76 (s, 6H), 3,51 (d, 2H), and 3.31 (m, 2H), 2,69 (m, 2H), 2.0 (m,2H), to 1.15 (d, 6H) ppm
N3-{4-[3-(2,6-Dimethylmorpholine-4-yl)propoxy] - for 3,5-acid}-1-(2-forfinal)-1H-[1,2,4]triazole-3,5-diamineS*3501,201,90(500MHz, DMSO-d6) of 9.75 (s,1H), 8,80 (s, 1H), 7,56 (dt, 1H), 7,45 (m, 2H), 7,34 (dt, 1H), 6,94 (s, 2H), 6.42 per (s, 2H), 3,81 (m, 4H), 3,70 (s, 6H), 3,50 (d, 2H), 3,32 (m, 2H), to 2.67 (m, 2H), 1,99 (m,2H), 1,15 (d, 6H) ppm
N3-[4-(4-Diethylaminoethoxy)for 3,5-acid]-1-(2-forfinal-1H-[1,2,4]triazole-3,5-diamineS*3473,201,90(500 MHz, DMSO-d6) of 9.00 (s, 1H), 8,76 (s, 1H), 7,55 (dt, 1H), 7,44 (m, 2H), 7,33 (dt, 1H), 6,93 (s, 2H), 6,41 (s, 2H), of 3.78 (t, 2H), 3,69 (s, 6H), of 3.13 (m, 6H), of 1.78 (m, 2H), 1,65 (m, 2H) ppm
4-{5-Amino-3-[4-(4-diethylaminoethoxy)for 3,5-dimethoxyaniline][1,2,4]triazole-1-yl}benzonitrileS*3480,202,10500 MHz, DMSO-d6) 9,05 (s, 1H), 8,98 (s, 1H), 7,94 (d, 2H), 7,80 (d, 2H), 7,00 (s, 2H), for 6.81 (s, 2H), 3,80 (t, 2H, in), 3.75 (s, 6H), of 3.13 (m, 6H), of 1.80 (m, 2H), 1,64 (m, 2H), 1,21 (t, 6H)
N3-[3,5-Dimethoxy-4-(3-morpholine-4-ylpropionic)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3456,201,90(500 MHz, DMSO-d6) to 9.66 (s, 1H), 9,05 (s, 1H), to 8.41 (DD, 1H), 7,97 (m, H), 7,71 (s, 2H), 7,65 (d, 1H), 7,21 (m, 1H), for 6.81 (s, 2H), 4.00 points (d, 2H), 3,86 (t, 2H), 3,80 (s, 6H), of 3.65 (t, 2H), 3,49 (d, 2H), 3,36 (m, 2H), 3,14 (m, 2H), 2,00 (m, 2H)
N3-[4-(3-Diethylaminopropyl)for 3,5-dimethoxy enyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine And3442,202,00(500 MHz, DMSO-d6) 9,10 (s, 1H), 9,05 (s, 1H), to 8.41 (DD, 1H), 7,97 (dt, H), 7,71 (s, 2H), 7,65 (d, 1H), 7,21 (m, 1H), 7,06 (s, 2H), 3,88 (t, 2H), 3,80 (s, 6H), 3,30 (m, 2H), 3,18 (m, 4H), of 1.94 (m, 2H), 1,22 (t, 6H)
N3-{3,5-Dimethoxy-4-[3-(4-methylpiperazin-1-yl)propoxy]phenyl}-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3469,201,50(500 MHz, DMSO-d6) 9,05 (s, 1H), to 8.41 (DD, 1H), of 7.97 (dt, 1H), of 7.70 (s, 2H), to 7.64 (d, 1H), 7,21 (m, 1H), 7,06 (s, 2H), 3,85 (t, 2H), 3,79 (s, 6H), 2,8-3,7 (width, 8H), of 2.81 (s, 2H), was 1.94 (m, 2H)
N3-[3,5-Dimethoxy-4-(4-(morpholine-4-yl)butoxy)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3470,302,00(500 MHz, DMSO-d6) to 9.70 (s, 1H), remaining 9.08 (s, 1H), to 8.41 (DD, 1H), of 7.97 (dt, 1H), of 7.70 (s, 2H), 7,65 (d, 1H), 7,21 (m, 1H), 7,05 (s, 2H), 3,99 (d, 2H), 3,81 (m, 2H), 3,79 (s, 6H), 3,66 (t, 2H), 3.45 points (d, 2H), 3,18 (m, 2H), of 3.07 (m, 2H), of 1.85 (m, 2H), 1,65 m
1-Benzotriazol-2-yl-N3-(2-methoxy-4-morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineIn, G3424,203,43(DMSO-d6, 500 MHz) of 8.04 (d, 1H), 7,86 (m, 2H), 7,79 (s, 2H), 7,50 (m, 2H), was 7.36 (t, 1H), 6,74 (s, 1H), 6,59 (d, 1H), 3,86 (s, 3H), of 3.77 (m, 4H), 3,14 (m, 4H)
N3-(4-(Morpholine-4-ylphenyl)-1-(3-phenoxyphenyl-1H-[1,2,4]triazole-3,5-diamineD, G3429,202,81(500 MHz, DMSO-d6) 8,80 (Shir. s, 1H), 7,46 (m, 5H), 7,35 (d, H), 7,21 (m, 2H), 7,12 (d, 2H), 7,02 (Shir. s, 2H), 6.90 to (DD, 1H), 6,5 (Shir. s, 2H), 3,79 (m, 4H), of 3.13 (m, 4H) ppm
N3-(2-Methoxy-4-morpholine-ylphenyl)-(4-cryptomaterial-2-yl)-1H-[1,2,4]triazole-3,5-diamineD*3442,203,23(DMSO-d6, 500 MHz) 8,11 (s, 1H), 7,78 (d, 1H), 7,51 (s, 1H), 7,47 (s, 2H), 6,70 (s, 1H), 6,55 (d, 1H), 3,84 (s, 3H), 3,76 (m, 4H), 3,11 (m, 4H)
1-(6-Methoxybenzothiazole-2-yl)-N3-(2-methoxy-4-morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineF3454,103,35(500 MHz, DMSO-d6) 7,86 (d, 1H), of 7.75 (d, 1H), of 7.70 (s, 2H), to 7.64 (d, 1H), 7,46 (s, 1H), to 7.09 (DD, 1H), 6.73 x (s, 1H), return of 6.58 (d, 1H), 3,86 (s, 3H), 3,83 (s, 3H), of 3.77 (m, 4H), of 3.13 (m,4H)
1-(4-Utiltity-2-yl)-N3-(2-methoxy-4-morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineD*3402,303,11(500 MHz, DMSO-d6) 7,79 (d, 1H), 7,50 (s, 2H), 7,27 (s, 1H), 6,92 (s, 1H), only 6.64 (d, 1H), 6,50 (DD, 1H), 3,84 (s, 3H), 3,74 (m, 4H), 3,06 (m, 4H), 2,68 (square, 2H),, of 1.23 (t, 3H)
1-(4-tert-Butylthiazole-2-yl)-N5-(2-methoxy-4-morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineB, G3430,203,95(500 MHz, DMSO-d6) of 10.3 (s, 1H), compared to 8.26 (d, 1H),, 6,91 (s, 1H), 6,72 (d, 1H), is 6.54 (DD, 1H), 5,94 (s, 2H), 3,93 (s, 3H), of 3.75 (m,4H), 3,10 (m, 4H), to 1.37 (s,9H)
4-[5-Amino-3-(4-deformedarse-3-isopropoxyaniline){1,2,4]triazole-1-yl]benzonitrileE3 401,303,86(500 MHz, DMSO-d6) of 9.09 (s, 1H), 7,95 (d, 2H), 7,79 (d, 2H), 7,54 (s, 1H), 7,02 (m, 2H), at 6.84 (t, 1H), 6,79 (Shir. s, 2H), 4,51 (m, 1H), 1,33 (d, 6H)
N3-(4-Deformedarse-3-isopropoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineD1377,304,00(500 MHz, DMSO-d6) 9,13 (s, 1H), to 8.41 (DD, 1H), 7,99 (m, 1H), 7,66 (m, 3H), 7,21 (m, 1H), 7,10 (DD, 1H), 7,03 (d, 1H), 6,85 (t,1H), 4,55 (m, 1H), 1,36 (d,6H)
N3-(3-Deformedarse-4-isopropoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineD3377,303,95(500 MHz, DMSO-d6) of 9.09 (s, 1H), to 8.41 (DD, 1H), 7,98 (dt, 1H), 7,65 (d, 1H), to 7.64 (Sirs, 2H), 7,60 (d, 1H), 7,38 (DD, 1H), 7,20 (dt, 1H), 7,05 (d, 1H), 7,00 (t, 1H), 4,43 (m, 1H), 1,25 (d, 6H)
N3-(4-(Morpholine-4-ylphenyl)-1-(4-piperidine-1-Yeremey-2-yl)-1H-[1,2,4]triazole-3,5-diamineD3422,301,67(500 MHz, DMSO-d6) remaining 9.08 (s, 1H), of 8.09 (d, 1H), to 7.64 (s, 2H), 7,58 (d, 2H), 6,94 (s, 2H), PC 6.82 (d, 1H, in), 3.75 (s, 8H), of 3.07 (s, 4H), by 1.68 (m, 2H), 1,62 (m, 4H)
4-[5-Amino-3-(3-deformedarse-4-isopropoxyaniline){1,2,4]triazole-1-yl]benzonitrileE3401,303,82(500 MHz, DMSO-d6) 9,03 (s, 1H), 7,94 (d, 2H), 7,79 (d, 2H), 7,50 (d, 1H), was 7.36 (DD,1H),? 7.04 baby mortality (d, 1H),, 6,97 (t, 1H), 6,78 (s, 2H), 4,42 (m, 1H), 1,24 (d, 6H)
1-[2-(4-methylpiperazin-1-yl)pyrimidine-4-yl]-N3-4-morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine G3437,301,50(500 MHz, DMSO-d6) cent to 8.85 (s, 1H), of 8.37 (d, 1H), 7,53 (s, 2H), of 7.48 (d, 2H), 6.87 in (d, 2H), 6,83 (d, 1H), and 3.72 (m, 4H), 3,68 (m, 4H), 2,99 (m, 4H), 2,39 (m, 4H), 2,22 (s, 3H)
N3-(4-(Morpholine-4-ylphenyl)-1-(2-piperidine-1-Yeremey-4-yl)-1H-[1,2,4]triazole-3,5-diamineD3436,301,68(500 MHz, DMSO-d6) 9,42 (s, 1H), scored 8.38 (d, 1H), to 7.67 (d, 2H), 7,63 (s, 2H), 7,38 (d, 2H), 6,83 (d, 1H), 4.26 deaths (m, 2H), 3.96 points (d, 2H), 3,70 (m, 4H), 3,62 (t, 2H), 3.27 to (d, 2H), is 3.08 (m, 2H), 1,64 (m,2H), 1.57 in (m,4H)
N3-(4-(Morpholine-4-ylphenyl)-1-(4-piperidine-1-Yeremey-2-yl)-1H-[1,2,4]triazole-3,5-diamineD3436,301,01(500 MHz, DMSO-d6) 9,34 (s, 1H), 8,13 (d, 1H), 7,72 (d, 2H), to 7.67 (s, 2H), 7,35 (d, 2H), of 6.71 (d, 1H), 4,25 (m, 2H), 3,97 (d, 2H), 3,71 (m, 4H), 3,62 (t, 2H), 3,26 (d, 2H), of 3.07 (m, 2H), by 1.68 (m, 2H), 1,59 (m, 4H)
1-[2-(4-methylpiperazin-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylmethylene)-1H-[1,2,4]triazole-3,5-diamineD3(500 MHz, DMSO-d6) 9,42 (s, 1H), 8,46 (d, 1H), to 7.67 (d, 2H), 7,53 (s, 2H), 7,37 (d, 2H), 7,00 (d, 1H), 4,6 (m, 2H), 4,25 (m, 2H), 3,97 (d, 2H), 3,62 (t, 2H), 3,53 (d, 2H), 3,25 (m, 4H), to 3.09 (m, 4H), 2,86 (s, 3H)
1-Pyridin-2-yl-N3-(4-pyrrolidin-1-ylmethylene)-1H-[1,2,4]triazole-3,5-diamineB3336,201,65(500 MHz, DMSO-d6) to 9.32 (s, 1H), 8,42 (m, 1H), 7,97 (m, 1H), 7,68 (m, 5H), 7,38(d, 2H), 7.23 percent (m, 1H), 4,25 (d, 2H), 3,35 (m, 2H), is 3.08 (m, 2H), 2,03 (m, 2H), of 1.85 (m, 2H)
N3-[4-(1-Morpholine-4-retil)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineB32,72(500 MHz, DMSO-d6) 9,36 (s, 1H), 8,42 (m, 1H), 7,99 (dt, 1H), 7,69 (m, 5H), 7,39 (d, 2H), 7,22 (m, 1H), 4,43 (m, 1H), 4.00 points (d, 1H), 3,91 (d, 1H), 3,69 (t, 1H), 3,60 (t, 3H), of 3.00 (m, 2H), 2,84 (m, 1H), 1,65 (d, 3H)
1-Pyridin-2-yl-N3-[4-(1-pyrrolidin-1-iletiler]-1H-[1,2,4]triazole-3,5-diamineB3350,202,81(500 MHz, DMSO-d6) 9,31 (s, 1H), 8,42 (DD, 1H), 7,98 (dt, 1H), 7,68 (m, 5H), 7,38 (d, 2H), 7,22 (m,1H), 4,34 (m, 1H), 3,62 (m, 1H), equal to 2.94 (m, 2H), 2,01 (m, 1H), 1,90 (m, 2H), 1,78 (m, 1H) to 1.61 (d, 3H)
N3-[4-(3-Diethylaminopropyl)-3-methoxyphenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineD3412,30, 412,201,90, 1,78(500 MHz, DMSO-d6) to 9.15 (s, 1H), 8,97 (s, 1H), to 8.41 (m, 1H), 7,97 (m, 1H), to 7.67 (m, 2H), 7,43 (s, 1H), 7,21 (m, 1H), 7,11 (m, 1H), 6,91 (m, 1H), 3,99 (t, 2H), 3,80 (s, 3H), 3,1-3,3 (m, 6H), 2,03 (m, 2H), to 1.21 (t, 6H)
N3-[4-(4-Methylpiperazin-1-ylmethyl)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineB2365,30, 365,200,17, 2,04(500 MHz, DMSO-d6) 9,27 (s, 1H), 8,42 (m, 1H), 7,98 (m, 1H), to 7.67 (m, 5H), 7,30 (m, 2H), 7,22 (m, 1H), 3,98 (width, 2H), 3,3 (width, 8H), and 2.79 (s, 3H)
N3-(4-(Morpholine-4-ylmethylene)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineB/td> 1352,200,24(DMSO-d6, 500 MHz) 9,80 (Shir. s, 1H), 9,42, (s, 1H), 8,42 (d, 1H), 7,99 (m, 1H), 7,72 (m, 2H), 7,69 (d, 2H), 7,37 (d, 2H), 7.23 percent (m, 2H), 7,24 (m, 1H), 4.26 deaths (m, 2H), 3,97 (m, 2H), 3,61 (m, 2H), 3.27 to (m, 2H), to 3.09 (m, 2H)
1-Benzothiazol-2-yl-N3-(3,4-acid)-1H-[1,2,4]triazole-3,5-diamineA*2369,103,70, 3,70, 3,70(500 MHz, DMSO-d6) which 9.22 (s, 1H), of 8.06 (s, 1H), a 7.85 (d, 1H), 7,79 (s, 2H), 7,51 (t, 1H), of 7.48 (DD, 1H), was 7.36 (m, 1H), 7,03 (DD, 1H),, to 6.88 (d, 1H), 3,81 (s, 3H), 3,71 (s, 3H)
4-{5-Amino-3-[4-(3-diethylaminopropyl)for 3,5-dimethoxyaniline]-[1,2,4]triazole-1-yl}benzonitrileC*3466,201,90, 2,00(500 MHz, DMSO-d6) 9,05 (s, 1H), 9,00 (s, 1H),7,94 (d, 2H), 7,80 (d, 2H), 7,01 (s, 2H), PC 6.82 (s, 2H), a 3.87 (t, 2H), 3,76 (s, 6H), and 3.31 (m, 2H), 3,18 (m, 4H), of 1.94 (m, 2H), 1,22 (t, 6H) ppm
N3-(3,4-Acid)-1-(2-piperidine-1-Yeremey-4-yl)-1H-[1,2,4]triazole-3,5-diamineA3397,202,90(500 MHz, DMSO-d6) 8,98 (s, 1H), 8,35 (d, 1H), 7,63 (s, 2H), was 7.36 (d, 1H), 7,10 (DD, 1H), 6,86 (d,1H), 6,80 (d, 1H), 3,76 (s, 3H), of 3.69 (s, 5H), 1,64 (, 2H), 1.57 in (m, 4H) ppm
N3-Benzo[1,3]dioxol-5-yl-1-(2-piperidine-1-Yeremey-4-yl)-1H-[1,2,4]triazole-3,5-diamineA3381,103,20(500 MHz, DMSO-d6) 9,07 (s, 1H), at 8.36 (d, 1H), 7,63 (s, 2H), 7,29 (d, 1H),? 7.04 baby mortality (m, 1H), 6,80 (m, 2H), 5,94 (s, 2H), 3,69 (SIRM, 4H), 1,65, (m, H), of 1.57 (m, 4H) ppm
N3-Benzo[1,3]dioxol-5-yl-1-(4-piperidine-1-Yeremey-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd3381,102,30(500 MHz, DMSO-d6) 9,19 (s, 1H), 8,10 (d, 1H), to 7.67 (Shir. s, 2H), 7,47 (d, 1H), 7,03 (m, 1H), 6,80 (m, 2H), 5,95 (s, 2H), 3,76 (Shir. m, 4H), by 1.68 (m, 2H), 1,62 (m, 4H) ppm
N3-(4-Diethylaminophenyl)-1-(2-piperidine-1-Yeremey-4-yl)-1H-[1,2,4]triazole-3,5-diamineAnd3408,202,00(500 MHz, DMSO-d6) 10,9 (Shir. s, 1H), 9,63 (Sirs, 1H), 8,39 (d,1H), to 7.77 d, 2H), 7,68 (s, 1H), 7,51 (d, 2H), 6,86 (d, 2H), 3,70 (m, 4H), 3,62 (m, 2H), 3,51 (m, 2H), 1,65 (m, 2H), 1.57 in (m, 4H), and 1.00 (t, 6H) ppm
N3-(3,4-Acid-1-(4-piperidine-1-Yeremey-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd3397,202,20(500 MHz, DMSO-d6) of 9.00 (s, 1H), of 8.09 (d, 1H), of 7.70 (s, 2H), 7,50 (s, 1H), to 7.09 (s, 1H), 6,83 (d, 1H), 6.75 in (d, 1H), 3,76 (s, 7H), of 3.69 (s, 3H), 1,67 (m, 2H), 1,60 (m, 4H) ppm
1-Benzothiazol-2-yl-N3-(4-diethylaminophenyl)-1H-[1,2,4]-triazole-3,5-diamineA*3380,102,50(500 MHz, DMSO-d6) 11,0 (Shir. s, 1H), 9,88 (s, 1H), 8,07 (d, 1H), 7,88 (d, 2H), 7,76 (d, 2H), 7,52 (m, 3H), 7,38 (m, 1H), to 3.64 (m, 2H), 3,53 (m, 2H), 1,01 (t,6H) ppm
N3-Benzo[1,3]dioxol-5-yl-1-(4-phenylthiazol-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd2,3379,104,20(500 M is C, DMSO-d6) which 9.22 (s, 1H), 8,02 (d, 2H), 7,80 (s, 1H), 7,63 (s, 2H), 7,46 (t, 2H), 7,37 (t, 1H), 7,30 (d, 1H), 6,98 (DD, 1H), 8,84 (d, 1H), 5,95 (s, 2H) ppm
N3-(4-Diethylaminophenyl)-1-(4-phenylthiazol-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd3406,102,70(500 MHz, DMSO-d6) 11,2 (Shir. s, 1H), 10,2 (Shir. s, 1H), 7,8-8,0 (m, 5H), 7,65 (Shir. m, 1H), 7,52 (m, 2H), 7,41 (m, 1H), 6,10 (m, 2H), 3,55 (Shir. m, 4H), of 1.03 (m, 6H) ppm
N3-(4-Diethylaminophenyl)-1-(4-piperidine-1-Yeremey-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd3408,201,60(500 MHz, DMSO-d6) 11,1 (Shir. s, 1H), 9,63 (Shir. s, 1H), 8,14 (d, 1H), 7,82 (d, 2H), 7,73 (s, 1H), of 7.48 (s, 2H), 6,77 (d, 1H), to 3.73 (m, 4H), 3,62 (m, 2H), 3,51 (m, 2H), by 1.68 (m, 2H), 1,60 (m, 4H), and 1.00 (t, 6H) ppm
6-[5-Amino-3-(4-diethylaminobenzylidene)-[1,2,4]triazole-1-incotinenceAnd2,3349,201,90(500 MHz, DMSO-d6) 11,0 (Shir. s, 1H), 9,73 (Sirs, 1H), 8,86 (s, 1H), 8,42 (d, 1H), to $ 7.91 (s, 1H), 7,82 (m, 3H), 7,52 (d, 2H), 3,63 (Shir. m, 2H), 3,52 (Shir. m, 2H), and 1.00 (t, 6H) ppm
N3-(3,4-Acid)-1-(4-phenylthiazol-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd2,3395,204,00(DMSO-d6, 500 MHz) becomes 9.97 (s, 1H), 8,00 (d, 2H), 7,82 (s, 1H), 7,51 (t, 2H), 7,39 (m, 2H), 7,21 (DD, 1H), 6,99 (d, 1H), 3,83 (s, 3H), 3,76 (s, 3H) ppm
N3-(3,4-Dimethoxyphenethyl)-1H-[1,2,4]triazole-3,5-diamineAnd3(DMSO-d6, 500 MHz) 12,5 (Shir. s, 1H), 9,3 (Sirs, 1H), 7.5 (Sirs, 2H), was 7.08 (d, 1H), 6,94 (DD, 1H), 6.89 in (d, 1H), of 3.73 (s, 3H), 3,70 (s, 3H) ppm
1-(2-Forfinal)-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineA*2355,001,60(DMSO-d6, 500 MHz) 8,56 (s, 1H), 7,4-of 7.55 (m, 2H), 7,38 (d, 2H), 7,33 (t, 1H), for 6.81 (d, 2H), 6,28 (s, 2H), 3,71 (m, 4H), 2.95 and (m, 4H) ppm
1-[4-(5-amino-1-pyridin-2-yl-1H-[1,2,4]thiazol-3-ylamino)phenylethaneAnd2295,202,90(DMSO-d6, 500 MHz) 9,73 (s, 1H), 8,43 (m, 1H), 8,01 (m, 1H), 7,89 (d, 2H), to 7.75 (m, 2H), 7,71 (d, 2H), 7,24 (m, 1H), 2,50 (s, 3H) ppm
N3-(2,4-Acid)-1-(forfinal)-1H-[1,2,4]triazole-3,5-diamineA*2330,102,70(DMSO-d6, 500 MHz) 7,83 (d, 1H), 7,53 (m, 1H), of 7.48 (m, 1H), 7,41 (m, 1H), 7,33 (m, 1H), 6,86 (s, 1H),, to 6.58 (d, 1H), 6,44 (DD, 1H), 6,34 (s, 2H), of 3.84 (s, 3H), 3,70 (s, 1H) ppm

[4-(5-amino-1-pyridin-2-yl-1H- [1,2,4]triazole-3-ylamino)phenyl] -phenylmethanoneAnd3357,103,70(DMSO-d6, 500 MHz) 9,82 (s, 1H), 8,43 (m, 1H), 7,98 (m, 1H), to 7.77 (m, 7H), of 7.69 (d, 1H), to 7.64 (t, 1H), 7,55 (t, 2H), 7,24 (m, 1H) ppm
1-(2-Forfinal)-N3-(4-(morpholine-4-ylmethylene)-1H-[1,2,4]triazole-3,5-diamineA*3&x0200A; (DMSO-d6, 500 MHz) 9,60 (Shir. s, 1H), 9,19, (s, 1H), 7,55 (d, 2H), 7,50 (m, 1H), 7,43 (m, 1H), 7,35 (m, 1H), 7,30 (m, 2H), 6,40 (s, 2H), 4,22 (m, 2H), 3,95 (m, 2H)and 3.59 (m, 2H), 3,24 (m, 2H), is 3.08 (m, 2H) ppm
N3-(3-Morpholine-4-ylmethylene)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3(DMSO-d6, 500 MHz) to 9.91 (Shir. s, 1H), 9,38, (s, 1H), 8,43 (m, 1H), 7,99 (m, 1H), 7,72 (m, 3H), to 7.67 (s, 1H), 7,37 (t, 1H), 7,24 (m, 1H), 6,98 (d, 1H), 4,33 (m, 2H), 3,98 (m, 2H), to 3.64 (m, 2H), 3,32 (m, 2H), 3,17 (m, 2H) ppm
1-(2-Forfinal)-N3-(3-morpholine-4-ylmethylene)-1H-[1,2,4]triazole-3,5-diamineA*3(DMSO-d6, 500 MHz) 9,79 (Shir. s, 1H), 9,14, (s, 1H), to 7.61 (d, 1H), 7,55 (m, 3H), 7,43 (m, 1H), 7,35 (m, 1H), 7,30 (m, 1H), 6.90 to (d, 1H), 6,40 (s, 2H), 4,25 (m, 2H), 3,93 (m, 2H), 3,60 (m, 2H), 3.27 to (m, 2H), 3,13 (m, 2H) ppm

N3-(3,4-Acid)-1-(2-piperidine-1-Yeremey-4-yl)-1H-[1,2,4]triazole-3,5-diamineAnd2397,103,30(DMSO-d6, 500 MHz) at 8.36 (d, 1H), 7,95 (d, 1H), 7.62mm (s, 2H), 7,,24 (s, 1H), 6,78 (d, 1H), is 6.61 (d, 1H), of 6.52 (DD, 1H), 3,84 (s, 3H), of 3.73 (s, 3H), of 3.69 (m, 4H), and 1.63 (m, 2H), and 1.56 (m, 4H) ppm
N3-(3,4-Acid)-1-quinoline-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1363,103,60(DMSO-d6, 500 MHz) 3,7 1 (s, 3H), 3,80 (s, H), 6,89 (d, 1H), 7,19-7,21 (DD, 1H), 7,39 (d, 1H), 7,32-of 7.55 (m, 1H), 7,94 (d, 1H), of 7.96 (d, 1H), 8,03 (s, 2H), 8,08 (d, 1H), charged 8.52 (d, 1H), 8,93 (s, 1H)
N3-(4-Diethylaminophenyl)-1-quinoline-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1374,202,40(DMSO-d6, 500 MHz) of 1.06 (t, 6H), 3,26 (square, 4H), of 6.68 (d, 2H), 7,49 (d, 2H), 7,53 (d, 1H), 7,74-to 7.77 (m, 1H), 7,94-7,98 (m, 4H), with 8.05 (d, 1H), 8,49 (d, 1H), 8,69 (s, 1H)
N3-(3,4-Acid)-1-(6-methylpyridin-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd1327,203,10(DMSO-d6, 500 MHz) of 2.51 (s, 3H), of 3.69 (s, 3H), of 3.77 (s, 3H), 6,85 (d, 1H), 7,03 (d,1H), 7,12-7,14 (DD, 1H), 7,38 (d, 1H), 7,47 (d, 1H), to 7.67 (s, 2H), to 7.84 (t, 1H), cent to 8.85 (s, 1H)

368,25
N3-(4-Diethylaminophenyl)-1-(6-methylpyridin-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd1338,302,10(DMSO-d6, 500 MHz) 1,04 (C, 6N), of 2.50 (s, 3H), 3,24 (square, 4H), of 6.65 (d, 2H), 7,03 (d, 1H), 7,45 (d, 1H), 7,47 (d, 2H), 7.62mm (s, 2H), 7,83 (t, 1H), at 8.60 (s, 1H)
N3-(4-Isopropoxyphenyl)-1-quinoline-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd2361,2(DMSO-d6, 500 MHz); to 8.94 (s, 1H), 8,31 (d, 1H), 8,1-7,9 (m, 5H), 7,76 (t, 1H), 7,60-7,52 (m, 3H), 6.90 to-PC 6.82 (m, 2H), 4.53-in is 4.45 (m, 1H), 1,89 (d, 6N)
N3-(4-Diethylaminophenyl)-1-(6-ethoxypyridine-2-yl)-1H-[1,2,4]triazole-3,5-diamineMethod And2
N3-(4-Dimethoxyphenyl)-1 -(6-methylpyrimidin-4-yl)-1H-[1,2,4]triazole-3,5-diamineMethod And1390,153,60d6-DMSO 3,71 (s, 3H), 3,86 (s, 3H), 6.90 to (d, 1H), 7,07-to 7.09 (DD, 1H), to 7.59-to 7.61 (m, 4H), to $ 7.91 (s, 2H), 8,02 (s, 1H), 8,13-8,16 (m, 2H), of 9.02 (s, 1H), 9,14 (s, 1H)
N3-(3,4-Acid)-1-(6-ethoxypyridine-2-yl)-1H-[1,2,4]triazole-3,5-diamineMethod And3357,203,43d6-DMSO of 1.37 (t, 3H), of 3.69 (s, 3H), 3,76 (s, 3H), 4,29 (square, 2H), 6,60 (d, 1H), 6,86 (d, 1H), 7,11-7,13 (DD, 1H), 7,21 (d, 1H), 7,37 (d, 1H), 7,43 (Sirs, 2H), 7,86 (t, 1H), 8,87 (s, 1H)

1-(3-Chloro-4-forfinal)-N3-(3,4-acid)-1H-[1,2,4]triazole-3,5-diamineThe way A*2364,093,13d6-DMSO to 3.67 (s, 3H), and 3.72 (s, 3H), 6,68 (Sirs, 2H), 6,83 (d, 1H), 7,07-to 7.09 (DD, 1H), 7.23 percent (d, 1H), 7,55 (t, 1H), 7,58-to 7.61 (m, 1H), 7,75-to 7.77 (DD, 1H), 8,77 (s, 1H)
N3-(3,4-Acid)-1-(4-methanesulfonyl)-1H-[1,2,4]triazole-3,5-diamineMethod And2390,062,10d6-DMSO of 3.25 (s, 3H), 3,71 (s, 3H), and 3.72 (s, 3H), to 6.88 (d, 1H),? 7.04 baby mortality-7,06 (DD, 1H), 7,12 (d, 1H), 7,82 (d, 2H), 8,02 (d, 2H), 8,97 (s, 1H)
4-[5-(Amino-3-(4-diethylaminobenzylidene)[1,2,4]triazole-1-yl]benzosulfimideThe way A* 2402,132,15d6-DMSO of 1.03 (t, 6N), 3,23 (square, 4H), 6,61-6,62 (m, 4H), 7,39-7,41 (m, 4H), 7,76 (d, 2H), 7,88 (d, 2H), charged 8.52 (s, 1H)
N3-(4-Diethylaminophenyl)-1-(4-methanesulfonyl)-1H-[1,2,4]triazole-3,5-diamineMethod And2401,102,10d6-DMSO 1,00 (t, 6N), 3,26 (s, 3H), 3,51 (Shir. s, 2H), 3,63 (Shir. s, 2H), 5,50 (Shir. s, 1H), 7,53 (Shir. s, 2H), to 7.64 (Shir. s, 2H), 7,83 (d, 2H), 8,02 (d, 2H), 9,48 (Shir. s, 1H), 11,10 (Sirs, 1H)
1-(3-Chloro-4-forfinal)-N3-(4-diethylaminophenyl)-1H-[1,2,4]triazole-3,5-diamineThe way A*3375,122,10d6-DMSO 0,991 (t, 6N), 3.46 in-3,51 (m, 2H), 3,39-of 3.60 (m, 2H), 6,66 (s, 1H), 7,47 (d, 2H), 7,54-to 7.61 (m, 2H), of 7.70 (d, 2H), 7,76-7,78 (DC, 1H), 9,44 (s, 1H), 10,90 (s, 1H)

2,83
3-[5-(Amino-3-(3,4-dimethoxyphenylthio)-[1,2,4]triazole-1-yl]benzonitrileThe way A*2337,102,70d6-DMSO 3,68 (s,3H), 3,76 (s, 3H), 6,70 (s, 2H), at 6.84 (d, 1H), 7,10 for 7.12 (DD, 1H), 7,28 (d, 1H), 7,66-7,72 (m, 2H), 7,92-7,94 (m, 1H), of 7.97 (s, 1H), 8,77 (s, 1H)
N-{4-[5-Amino-1-(6-methylpyridin-2-yl)-1H-[1,2,4]triazole-3-ylamino]phenylacetamideMethod And1324,142,54d6-DMSO 2,00 (s, 3H), of 2.50 (s, 3H), 7,06 (d, 1H), 7,43 (d, 2H), 7,51-rate of 7.54 (m, 3H), to 7.67 (s, 2H), to 7.84 (t, 1H), 8,99 (s, 1H), 9,73 (s,1H)
N3-(2-Fluoro-4-IU is oxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine Method And1301,153,21d6-DMSO 3,74 (s, 3H), 6,74-6,77 (DD, 1H), at 6.84-6.87 in (DD, 1H), 7.18 in-7,21 (m, 1H), 7,63 (d, 1H), to 7.67 (s, 2H), 7,93-7,98 (m, 2H), 8,29 (s, 1H), 8,39-to 8.40 (m, 1H)
N3-(2,4-Acid)-1-(6-methylpyridin-2-yl)-1H-[1,2,4]triazole-3,5-diamineMethod And1327,163,47d6-DMSO of 2.50 (s, 3H), of 3.73 (s, 3H), 3,85 (s, 3H), 6,52-is 6.54 (DD, 1H), 6,62 (d, 2H), 7,06 (d, 1H), 7,10 (s, 1H), of 7.48 (d, 1H), 7,69 (s, 2H), to 7.84 (t, 1H), 8,01 (d, 1H)
N3-(3,4-Acid)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineMethod And2313,153,28d6-DMSO of 3.77 (s, 3H), 3,81 (s, 3H), 6,62 (d, 1H), 7,02 (t, 1H), 7,21-7,24 (m, 1H), to 7.59 (s, 1H), 7,70-7,71 (m, 3H), 7,86 (d, 1H), of 7.96-of 8.00 (m, 1H), to 8.41-8,42 (m, 1H)
6-[5-Amino-3-(2,4-dimethoxyaniline)[1,2,4]triazole-1-yl]nicotinamideMethod And1338,103,40d6-DMSO 3,74 (s, 3H), of 3.84 (s, 3H), 6,00 (d, 1H), 6,62 (s, 1H), 7,35 (s, 1H), of 7.75 (d, 1H), to 7.84 (s, 2H), 7,98 (d, H), of 8.37 (d, 1H), 8,83 (s, 1H)
N3-(4-Methoxy-2-were)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineMethod And1297,102,90d6-DMSO 2,24 (s, 3H), 3,71 (s, 3H), 6,72-6,74 (m, 2H), 7,16-to 7.18 (m, 1H), 7,56 (d, 1H), to 7.61 (s, 2H), 7,66 (d, 1H), of 7.70 (s, 1H), to $ 7.91-7,94 (m, 1H), scored 8.38-8,39 (m, 1H)
N3-(4-Diethylamino-2-were)-1-pyridin-2-yl)-1H-[1,2,4]triazole-3,5-d is Amin Method And1338,201,75d6-DMSO of 1.06 (t, 6H), of 2.20 (s, 3H), 3.27 to (square, 4H), 6.48 in-6,50 (m, 2H), 7,15 (t, 1H), 7,44 (d, 1H), 7,50 (s, 1H), 7,53 (d, 1H), 7,56 (s, 2H), 7,88-to $ 7.91 (m, 1H), at 8.36 (d, 1H)
1-Pyridin-2-yl-N3-o-tolyl-1H-[1,2,4]triazole-3,5-diamineMethod And2267,20with 3.27d6-DMSO, and 2.27 (s, 3H), 6,86 (t, 1H), 7,11-7,16 (m, 2H), 7,19-7,21 (m, 1H), to 7.64 (d, 1H), 7,66 (s, 2H), 7,83 (s, 1H), 7,94-of 7.97 (m, 2H),8,40-to 8.41 (m, 1H)
1-Pyridin-2-yl-N3-5,6,7,8-tetrahydronaphthalen-yl-1H-[1,2,4]triazole-3,5-diamineMethod And1307,103,90d6-DMSO 1,67 was 1.69 (m, 2H), a 1.75-1.77 in (m, 2H), 2,63-of 2.66 (m, 2H), 2,70-of 2.72 (m, 2H), of 6.68 (d, 1H),? 7.04 baby mortality (t, 1H), 7.18 in-7,21 (m, 1H), 7,60-the 7.65 (m, 4H), to 7.77 (d, 1H), 7,93-to 7.95 (m, 1H), 8,39-to 8.40 (m, 1H)
N3-(2,4-Acid)-1-(6-methyl-4-triptorelin-2-yl)-1H-[1,2,4]triazole-3,5-diamineMethod And1395,104,30d6-DMSO 2,62 (s, 3H), 3,74 (s, 3H), of 3.84 (s, 3H), 6,55-to 6.57 (m, 1H), 6,61-6,62 (m, 1H), 7,25 (s, 1H), 7,44 (s,1H), 7.62mm (s, 1H), of 7.75 (s, 2H), to 7.93 (d, 1H)
N3-(2-Methoxy-4-morpholine-4-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineMethod And1368,202,30d6-DMSO was 3.05 (t, 4H), 3,74 (t, 4H), 3,85 (s, 3H), 6,50-of 6.52 (DD, 1H), is 6.61 (d, 1H), to 7.09 (s, 1H), 7,19-7,21 (m, 1H), to 7.67-to 7.68 (m, 3H), 7,95-7,98 (m, 2H), 8,39-to 8.40 (m, 1H)
N3-(2-Methoxy-4-Mohali the-4-ylphenyl)-1-(6-methylpyridin-2-yl)-1H-[1,2,4]triazole-3,5-diamine Method And1436,103,10d6-DMSO 3,05-of 3.07 (m, 4H), 3,74 is 3.76 (m, 4H), 3,85 (s, 3H), 6,50-of 6.52 (m, 1H), 6,66 (d, 1H), 7,25 (s, 1H), 7,60 (s, 2H), 7,71 (d, 1H), 7,95 (d, 2H), 8,24 (t, 1H)
1-(6-Methylpyridin-2-yl)-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineMethod And1406,102,83d6-DMSO of 3.00 (t, 4H), 3,74 (t, 4H), 6.89 in (d, 2H), 7,52 (d, 2H), 7,58 (s, H), of 7.70 (d, 1H), 7,95 (d, 1H), 8,25 (t, 1H), 8,96 (s, 1H)
N3-(2-Chlorophenyl)-1-(6-methylpyridin-2-yl)-1H-[1,2,4]triazole-3,5-diamineMethod F2355,104,35d6-DMSO of 6.96-6,99 (m, 1H), 7,32 and 7.36 (m, 1H), 7,44 was 7.45 (m, 1H), 7,68 (s, 2H), 7,65 (d, 1H), 7,98-to 7.99 (m,2H), 8,23-of 8.28 (m, 2H)
6-[5-Amino-3-(4-(morpholine-4-ilfenomeno)[1,2,4]triazole-1-yl]nicotinamideMethod F3363,202,16d6-DMSO 3,17 (Sirs, 4H), 3,80 (width, 4H), 7,10 (Shir. s, 2H), 7,58 (d, 2H), 7,76 (d, 1H), 7,85 (Shir. s, 2H), scored 8.38-to 8.41 (m, 1H), 8,84 (d, 1H), of 9.21 (Shir. s, 1H)
6-[5-Amino-3-(2-chlorpheniramine)[1,2,4]triazole-1-yl]nicotinamideMethod F3312,113,72d6-DMSO 6,97-7,00 (m, 1H), 7,32 and 7.36 (m, 1H), 7,43 was 7.45 (m, 1H), 7,78 (d, 1H), 7,92 (s, 2H), 8,21-8,23 (m, 1H), scored 8.38-to 8.41 (m, 1H), cent to 8.85 (d, 1H)
N3-(2,5-Acid)-1-(6-triptorelin-2-yl)-1H-[1,2,4]triazole-3,5-diamineMethod F 2381,114,03d6-DMSO of 3.75 (s, 3H), 3,82 (s, H), to 6.43-of 6.45 (m, 1H), 6,91 (d, 1H), 7,50 (s, 1H), to 7.67 (s, 2H), 7,74 (d, 1H), a 7.85 (d, 1H), to 7.93 (d, 1H), 8.30 to (t, 1H)
6-[5-Amino-3-(4-(morpholine-4-ilfenomeno)[1,2,4]triazole-1-yl]nicotinamideMethod And3381,201,50d6-DMSO 3,16 (Sirs, 4H), 3,80 (Shir. s, 4H), 7,09 (Shir. s, 2H), EUR 7.57-to 7.59 (m, 3H), 7,71 (d, 1H), 7,79 (Sirs, 2H), 8,14 (Shir. s, 1H), of 8.37-8,39 (m, 1H), 8,86-8,87 (m, 1H), 9,10 (Shir. s, 1H)
N3-(2-Chloro-5-methoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineMethod And1317,103,80d6-DMSO of 3.80 (s, 3H), 6,53-6,55 (m, 1H), 7.23 percent-7,26 (m, 1H), 7,32 (d, 1H), 7,65 (d, 1H), 7,71 (s, 1H), 7,78 (s, 2H), 7,98-8,02 (m, 2H), 8,42-8,44 (m, 1H)
6-[5-Amino-3-(2,5-dimethoxyaniline)-[1,2,4]triazole-1-yl]nicotinamideMethod F3338,143,43d6-DMSO 3,74 (s, 3H), 3,81 (s, 3H), to 6.43-6,46 (DD,1H), 6,91 (d, 1H), 7,54 (s, 1H), 7,71 (d, 1H), 7,83 (d, 1H), of 7.90 (s, 2H), to 8.41-8,44 (DD, 1H), 8,69 (d, 1H)
N3-(2,4-Dimethoxy-5-triptoreline)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineMethod And1381,103,90d6-DMSO are 3.90 (s, 3H), of 3.97 (s, 3H), 6,91 (s, 1H), 7,21-of 7.23 (m, 1H), 7,53 (s, 1H), 7,58 (d, 1H), 7,74 (s, 2H), 7,99-8,03 (m, 1H), to 8.41-8,42 (m, 1H), 8,44 (s, 1H)
N3-(2,5-Dimethoxy-4-morpholine-4-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-dia is n Method And1398,202,14d6-DMSO 2,93-2,95 (m, 4H), 3,71-to 3.73 (m, 4H), 3,82 (s, 3H), 3,83 (s, 3H), 6,63 (s, 1H), 7,20-of 7.23 (m, 2H), 7,65 (d, 1H), 7,72 (s, 2H), 7,97-of 8.00 (m, 2H), 8,40-to 8.41 (m, 1H)
4-{5-Amino-3-[3,5-dimethoxy-4-(2-morpholine-4-ylethoxy)phenylamino][1,2,4]triazole-1-yl}benzonitrileMethod1466,301,80d6-DMSO 2,46 (Shir. s, 4H), 2,58 (t, 2H), 3,56-to 3.58 (m, 4H), 3,74 (s, 6H), 3,86 (t, 2H), 6,80 (s, 2H), 6,99 (s, 2H), 7,80 (d, 2H), 7,94 (d, 2H), of 8.95 (s, 1H)
N3-[2,5-Dimethoxy-4-(2-morpholine-4-ylethoxy)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineMethod And1442,201,90d6-DMSO 2,49-of 2.50 (m, 4H), to 2.66 (t, 2H), to 3.58-of 3.60 (m, 4H), of 3.80 (s, 3H), 3,82 (s, 3H), 4,06 (t, 2H), 6,78 (s, 1H), 7,19-7,22 (m, 2H), 7,65 (d, 1H), 7,71 (s, 2H), of 7.96 to 8.0 (m, 2H), 8,40-to 8.41 (m, 1H)
4-{5-Amino-3-[3,5-dimethoxy-4-(2-morpholine-4-ylethoxy)phenylamino]-[1,2,4]triazole-1-yl}benzonitrileThe method*3466,211,93d6-DMSO 3,22-3,24 (m, 2H), 3,53-of 3.60 (m, 4H), 3.72 points-3,74 (m, 2H), of 3.77 (s, 3H), 3,82 (s, 3H), was 4.02-Android 4.04 (m, 2H), 4.26 deaths-to 4.28 (m, 2H), 6,86 (s, 3H), 7,34 (s, 1H), 7,78-7,79 (m, 2H), 7,94-of 7.97 (m, 2H), 7,98 (s, 1H), of 10.0 (s, 1H)
6-{5-Amino-3-[2-methoxy-4-morpholine-4-ilfenomeno]-[1,2,4]triazole-1-yl}nicotinamideMethod3411,06d6-DMSO 3,13 (Shir. s, 4H), 3,78 (Shir. s, 4H), a 3.87 (who, 3H), 6,62 (Shir. s, 1H), 6.75 in (lat. s, 1H), 7,37 (s, 1H), EUR 7.57 (s, 1H), 7,71 (d, 1H), to $ 7.91 (s, 2H), 8,00 (d,1H), 8,16 (s, 1H), of 8.37-8,39 (m, 1H), 8,86-8,87 (m, 1H)
6-[5-Amino-3-[2-methoxy-4-morpholine-4-ilfenomeno]-[1,2,4]triazole-1-yl}nicotinamideMethod2393,102,58d6-DMSO of 3.06 (s, 4H), 3,74 (s, 4H), 3,85 (s, 3H), 6,50-of 6.52 (m, 1H), 6,66 (s, 1H), 7,30 (s, 1H), 7,73-7,74 (m, 1H), 7,83 (s, 2H), 7,92-7,94 (m, 1H), of 8.37 is 8.38 (m, 1H), 8,82 (s, 1H)
1-(6-Methylpyridin-2-yl)-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineMethod352,252,31d6-DMSO of 2.50 (s, 3H), 2,99 (t,4H), to 3.73 (t, 4H), to 6.88 (d, 2H), 7,05 (d, 1H), 7,47 (d, 1H), 7,51 (d, 2H), 7,65 (s, 2H), to 7.84 (t, 1H), 8,80 (s, 1H)
N3-(4-Methoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3283,13,12DMSO(d6): 8,95 (Sirs, 1H), to 8.41 (DD, 1H), 7,99 (TD, 1H), 7,8 (m, 2H), 7,69 (d, 1H), 7,55 (m, 2H), 7,21 (DD, 1H), 6,86 (m, 2H), 3,70 (s, 3H)
N3-(3-Methoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3283,103,19DMSO(d6): 9,18 (Sirs, 1H), 8,42 (DD, 1H), 8,00 (TD, 1H), 7,8 (m, 2H), 7,68 (d, 1H), 7,37 (m, 1H), 7,24 (DD, 1H), 7,15 (m, 2H), to 6.43 (m, 1H, in), 3.75 (s, 3H)
Methyl ester of 4-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)benzoic acidAnd3311,13,26 (A) DMSO(d6): 9,74 (s, 1H), 8,42 (DD, 1H), 8,00 (TD, 1H), 7,87 (d, 2H), to 7.77 (width, s, 2H), of 7.75 (d, 1H), 7,72 (d, 2H), 7,24 (DD, 1H), 3,80 (s, 3H)
3-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)benzamideAnd3296,12,23DMSO(d6): of 9.30 (s, 1H), 8,42 (DD, 1H), 8,03 (m, 1H), 8,01 (TD, 1H), 7,86 (Sirs, 1H), to 7.84 (dt, 1H), to 7.77 (Shir. s, 2H), 7,73 (d, 1H), 7,31 (m, 2H), 7,27 (Shir. s, 1H), 7.23 percent (DD, 1H)
4-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-benzosulfimideAnd3332,12,36DMSO(d6): to 9.66 (s, 1H), 8,43 (DD, 1H), 8,00 (TD, 1H), 7,73 (m, 7H), 7.23 percent (DD, 1H), 7,12 (Shir. s, 2H),
3-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)benzosulfimideAnd3332,12,47DMSO(d6): 9,54 (s, 1H), 8,43 (DD, 1H), 8,19 (t, 1H), 8,00 (TD, 1H), 7,80 (DD, 1H), to 7.75 (m, 2H), 7,73 (d, 1H), 7,44 (t, 1H), 7,32 (s, 2H), 7,30 (d, 1H), 7.23 percent (DD, 1H)
N3-(2,4-Acid)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3313,23,16DMSO(d6): 8,44 (DD, 1H), 8,17 (Sirs, 2H), 8,01 (TD, 1H), to 7.99 (d, 1H), 7,72 (d, 1H), 7,63 (Sirs, 1H), 7,28 (DD, 1H), 6,65 (d, 1H), 6,55 (DD, 1H), 3,86 (s, 3H), of 3.73 (s, 3H)
N3-(3,4-Acid)-1-(2-forfinal)-1H-[1,2,4]triazole-3,5-diamineAnd3330,22,90 (A)DMSO(d6): at 8.60 (s, 1H), 7,54 (TD, 1H), 7,46 (m, 1H), 7,40 (t, 1H), 7,22 (t, 1H), 7,38 (d, 1H), 7,06 (DD, 1H), 6,79 (d, 1H), of 6.31 (s, 2H), 3,68 (s, 3H), 3,63 (s, 3H)
N-[4-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)phenyl]ndimethylacetamideAnd3338,13,09DMSO(d6): 9,74 (s, 1H), 9,05 (s, 1H), 8,40 (DD, 1H), 7,97 (TD, 1H), 7,73 (d, 1H, m, 2H), 7,53 (d, 2H), 7,45 (d, 2H), 7,20 (DD, 1H), 2,03 (s, 3H)
N-[3-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)phenyl]ndimethylacetamideAnd3310,22,77 (A)DMSO(d6): 9,86 (s, 1H, NH), 9,13 (s, 1H, NH), to 8.41 (DD, 1H), 7,99 (m, 2H), to 7.84 (d, 1H), to 7.75 (m, 2H, NH2), from 7.24 (d, 1H), 7,22 (DD, 1H), 7,13 (t, 1H), to 7.09 (d, 1H), 2,07 (s, 3H, CH3)
1-(2-Chlorophenyl)-N3-(3,4-acid)-1H-[1,2,4]triazole-3,5-diamineA*3346,22,90 (A)DMSO(d6): 8,55 (s, 1H), 7,65 (m, 1H), 7,53 (m, 1H), 7,49 (m, 2H), 7,17 (d, 1H), 7,07 (DD, 1H), 6,78 (d, 1H), 6,20 (s, 2H), 3,68 (s, 3H), of 3.65 (s, 3H), CDCl3: 7,5 (m, 2H), and 7.4 (m, 2H), and 7.1 (d, 1H), 6,9 (DD, 1H), 6,7 (d, 1H), 6,6 (Sirs, 1H), and 3.8 (s, 3H), and 3.7 (s, 3H)
N3-[4-Methoxy-3-(2-methoxyethoxy)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3357,22,96DMSO(d6): 8,88 (s, 1H), to 8.41 (DD, 1H), 7,97 (TD, 1H), 7,68 (m, 3H), of 7.36 (d, 1H), 7,21 (DD, 1H), 7,18 (DD, 1H), 6.89 in (d, 1H), 4,08 (t, 2H), 3,71 (s, 3H), 3,70 (t, 2H), 3.33 and (s, 3H)
N3-[3-Methoxy-4-(2-methoxyethoxy)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3357,2DMSO(d6): 8,90 (s, 1H), to 8.41 (DD, 1H), 7,97 (TD, 1H), 7,68 (m, 3H), 7,40 (d, 1H), 7,21 (DD, 1H), 7,12 (DD, H)6,86 (d, 1H), 3,99 (t, 2H), of 3.78 (s, 3H), 3,63 (t, 2H), 3,32 (s, 3H)
N3-[3,4-Bis-(2-methoxyethoxy)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3401,22,90DMSO(d6): 8,91 (s, 1H), to 8.41 (DD, 1H), 7,98 (TD, 1H), 7,68 (m, 3H), 7,39 (d, 1H), 7,21 (DD, 1H), 7,14 (DD, 1H), 6.89 in (d, 1H), 4,11 (t, 2H), a 4.03 (t, 2H), 3,70 (t, 2H), 3,62 (t, 2H), 3,35 (s, 3H), 3,32 (s, 3H)
N3-Phenyl-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3253,13,21DMSO(d6): 9,12 (s, 1H), to 8.41 (DD, H), 7,98 (TD, 1H), of 7.70 (d, 1H), 7,68 (width, s, 2H), 7,63 (d, 2H), 7,25 (m, 2H), 7,21 (DD, 1H), PC 6.82 (t, 1H)
N3-(3,5-Acid)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3313,13,19 (A)DMSO(d6): remaining 9.08 (s, 1H), to 8.41 (DD, 1H), 8,00 (TD, 1H), of 7.70 (s, 2H), to 7.64 (d, 1H), 7.23 percent (DD, 1H), 6.90 to (d, 2H), 6,03 (t, 1H), 6.73 x (s, 6H)
1-Pyridin-2-yl-N3-(3-triptoreline)-1H-[1,2,4]triazole-3,5-diamineAnd3321,13,86DMSO(d6): 9,58 (s, 1H), 8,42 (DD, 1H), 8,03 (s, 1H), 8,01 (TD, 1H), 7,87 (DD, 1H), of 7.70 (s, 2H), 7,66 (d, 1H), of 7.48 (t, 1H), 7.23 percent (DD, 1H), 7,15 (d, 1H)
N3-(4-Butoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3325,23,55 (A)DMSO(d6): 8,88 (s, 1H), 8,40 (DD 1H), of 7.97 (dt, 1H), to 7.67 (m, 3H), 7,52 (d, 2H), 7,17 (DD, 1H), for 6.81 (d, 2H), 3,90 (m, 2H), 1,67 (m, 2H), 1,42 (m,2H), of 0.93 (t, 3H)
N3-(3,5-Differenl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3289,13,37 (A)DMSO(d6): 9,41 (s, 1H), 8,42 (DD, 1H), 8,00 (TD, 1H), to 7.75 (m, 3H), 7,68 (d, 1H), 7,30 (m, 2H), 7.23 percent (DD, 1H)
1-(2-Forfinal)-N3-(3,4,5-trimethoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineS*3360,12,97 (A)1H-DMSO(d6): 8,71 (s, 1H), 7,56 (TD, 1H), 7,46 (m, 1H), 7,41 (TD, 1H), 7,32 (TD, 1H), 6,92 (s, 2H), 6,34 (s, 2H), 3,68 (s, 6H), 3,55 (s, 3H)
4-[5-Amino-3-(3,4,5-trimethoxybenzylamine)-1H-[1,2,4]triazole-1-yl]benzonitrileS*3367,2is 3.08 (A)1H-DMSO(d6): of 8.95 (s, 1H), 7,94 (d, 2H), 7,80 (d, 2H), 7,00 (s, 2H), 6,80 (s,2H), 3,82 (s,6H), of 3.56 (s, 3H), 8,93 (1H), 7,93 (J=8,7, 2H), 7,79 (J=8,7, 2H), 6,98 (2H), 6,79 (2H), of 3.73 (6H), 3,57 (3H), (500 MHz, DMSO-d6) 8,99 (s, 1H), 7,95 (d,2H), 7,80 (
4-[3-Amino-5-(3,4,5-trimethoxybenzylamine)-1H-[1,2,4]triazole-1-yl]benzonitrileS*3367,22,83 (A)1H-DMSO(d6): of 8.95 (s, 1H), 7,94 (d, 2H), 7,73 (d, 2H), 6,83 (s, 2H), ceiling of 5.60 (s, 2H), of 3.73 (s, 6H), of 3.60 (s, 3H)
N3-(4-Chloro-2,5-acid)1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3347,13,57 (A)DMSO(d6): 8,44 (DDD, 1H), 8,17 (s, 1H), 8,01 (TD, 1H), 7,88 (Shir. s, 2H, NH2), of 7.70 (s,1H), to 7.68 (d, 1H), 7,25 (DDD, 1H), was 7.08 (s, 1H), 3,90 (s, 3H), 3,83 (s, 3H)
N3-(5-Chloro-2-methoxyphenyl)1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3313,13,34DMSO(d6): to 8.45 (DD, 1H), they were 8.22 (d, 1H), with 8.05 (dt, 1H), 7,97 (m, 2H), 7,81 (s, 1H), 7,66 (d, 1H), 7,28 (DD, 1H), 7,00 (d, 1H), 6,92 (DD, 1H), with 3.89 (s, 3H)
2-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-4-tert-butylphenolAnd3325,23,53DMSO(d6): 11,17 (s, 1H), 9,85 (s, 1H), 8,49 (d, 1H), 8,42 (d, 1H), 7,98 (t, 1H), to 7.59 (d, 1H), 7,20 (m, 1H), 6,83 (d, 1H), 6,78 (d, 1H), 5,70 (Sirs, 2H), 1.28 (in s, 9H)
N3-(2-Methoxy-5-nitrophenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3328,13,51DMSO(d6): 9,20 (d, 1H), 8,45 (d, 1H), 8,10 (s, 1H), of 8.06 (t, 1H), 7,87 (DD, 1H), 7,81 (s, 2H), 7,69 (d, 1H), 7,26 (t, 1H), 7,20 (m, 1H), 4.00 points (s, 3H)
Methyl ester 3-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-4-methoxybenzoic acidAnd3341,13,29DMSO(d6): 8,90 (d, 1H), 8,43 (d, 1H), 8,03 (TD, 1H), 7,78 (s, 2H), 7,69 (d, 1H), to 7.64 (s, 1H), 7,55 (DD, 1H), 7,25 (DD, 1H), 7,11 (d, 1H), 3,92 (s, 3H), of 3.84 (s, 3H)
N3-(2-Methoxy-5-triptoreline)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3351,24,00DMSO(d6): 8,56 (d, 1H), 8,44 (d, H), with 8.05 (dt, 1H), 7,86 (s, 1H), to 7.84 (m, 2H), to 7.61 (d, 1H),7,25 (d, 1H), 7,24 (d, 1H), 7,17 (DD, 1H), of 3.97 (s, 3H)
3-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)biphenyl-4-olAnd3345,13,47DMSO(d6): 11,30 (s, 1H), 10,32 (width,s, 1H), 8,66 (d, 1H), 8,45 (DD, H), of 8.00 (dt, 1H), to 7.61 (d, 1H), EUR 7.57 (m, 2H), 7,45 (t, 2H), 7,30 (m, 1H), 7.23 percent (TD, 1H), 7,13 (DD, 1H), 6,98 (d, 1H), 5,80 (m, 2H)
1-Pyridin-2-yl-N3-(2,3,5-trimethoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd3343,13,21DMSO(d6): 8,46 (DD, 1H), 8,10 (m, 2H), 8,04 (TD, 1H), 7,95 (width,s, 1H), 7,69 (d, 1H), 7,53 (d, 1H), 7,28 (DD, H), and 6.25 (d, 1H), 3,82 (s, 3H), 3,79 (s, 3H), and 3.72 (s, 3H)
N3-(2,5-differenl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine3289,13,70DMSO(d6): 9,03 (s, 1H), 8,43 (DD, 1H), 8,12 (DDD, 1H), 8,01 (TD, 1H), 7,80 (width,s, 2H), 7,68 (d, 1H), 7,25 (DD, 1H), 7,20 (DDD, 1H), 6,69 (m, 1H)
N3-(2-Methoxy-5-triftorperasin)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3367,23,90 (A)DMSO(d6): 8,43 (DD, 1H), of 8.25 (d, 1H), 8,02 (TD, 1H), 7,85 (width, s, 2H, NH2), 7,81 (s, 1H, NH), a 7.62 (d, 1H), 7,26 (DD, 1H), 7,06 (d,1H), 6,85 (DD, 1H), 3,90 (s, 3H)
1-Pyridin-2-yl-N3-(2-deformational)-1H-[1,2,4]triazole-3,5-diamineAnd3337,103,90DMSO(d6): 8,63 (s, 1H), 8,42 (DD, 1H), 8,35 (DD, 1H), 8,00 (TD, 1H), 7,74 (width,s, 2H), 7,71 (d, 1H), 7,34(TD,1H), 7,31 (DD,1H), 7.23 percent (DD, 1H), 6,98 (TD, 1H)
N3-(2-Isopropoxy-5-methoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine3341,13,82DMSO(d6): 8,43 (DD, 1H), 8,02 (TD, 1H), 7,86 (m, 2H, NH2), a 7.85 (d, 1H), to 7.67 (d, 1H), 7,33 (s, 1H), 7,25 (DD, 1H), 6,94 (d, 1H), 6.42 per (DD, 1H), 4,55 (m, 1H), 3,74 (s, 3H), 1.28 (in s, 3H), 1.26 in (s, 3H)
N3-(2-Fluoro-5-morpholine-4-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine3356,23,248,49 (m, 1H), 8,40 (d, 1H), 8,00 (TD, 1H), of 7.90 (DD, 1H), 7,76 (width,s, 2H), to 7.61 (d, 1H), 7,22 (DD, 1H), 7,05 (DD, 1H), 6,50 (m, 1H), 3,78 (m, 4H), to 3.09 (m, 4H)
4-[5-Amino-3-(3,5-diisopropylamino)-[1,2,4]triazole-1-yl]benzonitrileD*3393,24,00 (A)DMSO(d6): of 8.92 (s, 1H), 7,95 (d, 2H), 7,80 (d, 2H), 6,77 (s, 2H), 6,76 (m, 2H), 5,95 (s, 1H), 4,47 (m, 2H), 1,21 (s, 6H), 1,22 (s, 6H)
4-[5-Amino-3-(3,5-dimethoxyaniline)-[1,2,4]triazole-1-yl]benzonitrileD*3335,2 (M-1)3,11DMSO(d6): 9,00 (s, 1H), 7,94 (d, 2H), 7,79 (d, 2H), 6,83 (d, 2H), 6,77 (m, 2H), 6,00 (t, 1H), 3,70 (s, 6H)

3-[5-Amino-3-(3,4,5-trimethoxybenzylamine)-[1,2,4]triazole-1-yl]benzonitrileD*3365,2 (M-1)2,74DMSO (d6): 8,86 (s, 1H), 7,98 (m, 1H), 7,94 (dt, 1H), 7,72 (dt, 1H), 7,6 (t, 1H), 6,97 (s, 2H), 6.75 in (m, 2H), 3.75 to (C, 6N), to 3.58 (s, 3H)
N-{3-Acetylamino-5-[5-amino-1-(4-cyanophenyl)-1H-[1,2,4]thiazol-3-ylamino]phenyl}ndimethylacetamideS*3341,22,05DMSO (d6): 9,76 (s, 2H), 8,97 (s, 1H), to 7.93 (d, 2H), of 7.90 (d, 2H), 7,54 (s, 2H), 7,40 (s, 1H), of 6.71 (s, 2H), 2,02 (C, 6N)
4-[5-Amino-3-(3,5-dimethoxy-4-methylphenylimino)-[1,2,4]triazole-1-yl]benzonitrileD*3to 351.33,50DMSO (d6): of 8.92 (s, 1H), to 7.93 (d, 2H), 7,80 (d, 2H), 6,97 (s, 2H), 6,8 (Shir. s, 2H), 3,74 (C, 6N), 1,91 (c, 3H),
N3-(3-Methoxy-4-morpholine-4-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineD3368,31,79DMSO (d6): 9,35 (Shir. s, 1H), 8,42 (DD, 1H), 8,00 (TD, 1H), to 7.77 (m, 2H), of 7.70 (d, 1H), to 7.61 (s, 1H), 7,32 (m, 1H), 7,22 (m, 2H), of 3.94 (s, 3H), 3,90 (m, 4H), to 3.38 (m, 4H),
4-[5-Amino-3-(3-methoxy-4-morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]benzonitrileD*3392,21,79DMSO (d6): 9,18 (Shir. s, 1H), 7,94 (d, 2H), 7,80 (d, 2H), 7,47 (s, 1H), 7,18 (Shir. s, 2H), for 6.81 (m, 2H), 3,78 (m, 7H), 3,90 (m, 4H), 3,20 (m, 4H)

338,1td align="center"> 2-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triethylamine)-4-tert-butylphenol
N3-(3,5-Acid)-1-(2-forfinal)-1H-[1,2,4]triazole-3,5-diamineD*3386,33,90DMSO(d6): 8,73 (s, 1H), 7,54 (TD, 1H), of 7.48 (m, 1H), 7,40 t, 1H), 7,32 (m, 1H), of 6.68 (d, 2H), 6.4 (m, 2H), 5,59 (m, 1H), 4,46 (m, 2H), 1,23 (s, 6H), to 1.21 (s, 6H)
N3-(3-Isopropoxy-4-morpholine-4-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineD3396,32,42DMSO(d6): 9,27 (s, 1H, NH), 8,42 (DD, 1H), 8,00 (TD, 1H), 7,73 (m, 2H, NH2), 7,63 (d, 1H), 7,60 (s, 1H), 7,22 (m, 2H), 7,14 (d, 1H), 4,69 (m, 1H), 3,90 (m, 4H), to 3.38 (m, 4H), of 1.42 (d, 6H)
4-[5-Amino-3-(3-isopropoxy-4-maronil-4-ilfenomeno)-[1,2,4]triazole-1-yl]benzonitrileD*3420,32,31DMSO(d6): 9,20 (s, 1H, NH), of 7.96 (d, 2H), 7,80 (d, 2H), 7,54 (s, 1H), 7,20 (m, 1H), 7,11 (DD, 1H), PC 6.82 (m, 2H), with 4.64 (m, 1H), 3,88 (m, 4H), to 3.34 (m, 4H), to 1.38 (d, 6H)
N3-(3-Isopropoxy-4-morpholine-4-ylmethylene)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineD*3410,33,00 (A)DMSO(d6): 9,36 (s, 1H, NH), 8,42 (DD, 1H), 8,00 (TD, 1H), of 7.70 (m, 2H, NH2), the 7.65 (d, 1H), 7.62mm (d, 1H), 7,30 (d, 1H), 7.23 percent (DD, 1H), 7,12 (DD, 1H), 4,63 (m, 1H), 4,20 (s, 2H), 3,97 (d, 2H), the 3.65 (t, 2H), of 3.31 (d, 2H), 3,10 (m, 2H), 1,41 (s, 3H), 1,40 (,
4-[5-Amino-3-(3-ISOProx-4-morpholine-4-iletilenlerin)[1,2,4]triazole-1-yl]benzonitrileD*3434,33,02DMSO(6): of 9.30 (s, 1H),7,95 (d, 2H), 7,79 (d, 2H), 7,58 (d, 1H), 7,28 (d, 1H), was 7.08 (DD, 1H), 6,80 (width, s, 2H, NH2), 4,60 (m, 1H), 4,18 (d, 2H), 3.96 points (d, 2H), to 3.64 (t, 2H), 7,30 (m, 2H), 3,10 (square, 2H), to 1.38 (d, 6H),
N3-[4-(1-Methylpyridin-4-yl)phenyl]-1-Piri is in-2-yl-1H-[1,2,4]triazole-3,5-diamine D3350,32,74 (A)DMSO(d6): 9,06 (s, 1H), to 8.41 (DD, 1H), 7,98 (TD, 1H), of 7.70 (d, 1H), 7,69 (m, 2H), 7,58 (d, 2H), 7,20 (DD, 1H), 7,10 (d, 2H), 3,50 (d, 2H), 3,06 (m, 2H), 2,81 (d, 3H), 2,70 (TT, 1H), 2,00 (d, 2H), 1,80 (m, 2H)
5-[5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-2-morpholine-4-evententryD3363,33,20DMSO(d6): to 9.32 (s, 1H), to 8.41 (d, 1H), 8,00 (TD, 1H), 7,95 (d, 1H), 7,80 (DD, 1H), 7,74 (m, 2H), 7,65 (d, 1H), 7,21 (DD, 1H), 7,18 (d, 1H), 3,76 (m, 4H), to 3.02 (m, 4H)
N3-(4-Methoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3283,13,12DMSO(d6): 8,95 (Shir. s, 1H), to 8.41 (DD, 1H), 7,99 (TD, 1H), 7,8 (m, 2H), 7,69 (d, 1H), 7,55 (m, 2H), 7,21 (DD, 1H), 6,86 (m, 2H), 3,70 (s, 3H)
N3-(3-Methoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3283,103,19DMSO(d6): 9,18 (Shir. s, 1H), 8,42 (DD, 1H), 8,00 (TD, 1H), 7,8 (m, 2H), 7,68 (d, 1H), 7,37 (m, 1H), 7,24 (DD, 1H), 7,15 (m, 2H), to 6.43 (m, 1H), 3,75 (s, 3H)
Methyl ester of 4-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)benzoic acidAnd3311,13,26 (A)DMSO(d6): 9,74 (s, 1H), 8,42 (DD, 1H), 8,00 (TD, 1H), 7,87 (d, 2H), to 7.77 (Shir. s, 2H), of 7.75 (d, 1H), 7,72 (d, 2H), 7,24 (DD, 1H), 3,80 (s, 3H)
3-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)benzamide And3296,12,23DMSO(d6): of 9.30 (s, 1H), 8,42 (DD, 1H), 8,03 (m, 1H), 8,01 (TD, 1H), 7,86 (Shir. s, 1H), to 7.84 (dt, 1H), to 7.77 (Shir. s, 2H), 7,73 (d, 1H), 7,31 (m, 2H), 7,27 (Shir. s, 1H), 7.23 percent (DD, 1H),
4-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-benzosulfimideAnd3332,12,36DMSO(d6): to 9.66 (s, 1H), 8,43 (DD, 1H), 8,00 (TD, 1H), 7,73 (m, 7H), 7.23 percent (DD, 1H), 7,12 (Shir. s, 2H)
3-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)benzosulfimideAnd3332,12,47DMSO(d6): 9,54 (s, 1H), 8,43 (DD, 1H), 8,19 (t, 1H), 8,00 (TD, 1H), 7,80 (DD, 1H), to 7.75 (m, 2H), 7,73 (d, 1H), 7,44 (t, 1H), 7,32 (s, 2H), 7,30 (d, 1H), 7.23 percent (DD, 1H),
N3-(2,4-Acid)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3313,23,16DMSO(d6): 8,44 (DD, 1H), 8,17 (width,s, 2H), 8,01 (TD, 1H), to 7.99 (d, 1H), 7,72 (d, 1H), 7,63 (width,s, 1H), 7,28 (DD, 1H), 6,65 (d, 1H), 6,55 (DD, 1H), 3,86 (s, 3H), of 3.73 (s, 3H)
N3-(3,4-Acid)-1-(2-forfinal)-1H-[1,2,4]triazole-3,5-diamineA*3330,22,90 (A)DMSO(d6): at 8.60 (s, 1H), 7,54 (TD, 1H), 7,46 (m, 1H), 7,40 (t, 1H), 7,22 (m, 1H), 7,38 (d, 1H), 7,06 (DD, 1H), 6,79 (d, 1H), 6,3l (s, 2H), 3,68 (s, 3H), 3,63 (s, 3H)
N-[4-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)phenyl]benzamideAnd33,09DMSO(d6): 9,74 (s, 1H), 9,05 (s, 1H), 8,40 (DD, 1H), 7,97 (TD, 1H), 7,73 (d, 1H, m, 2H), 7,53 (d, 2H), 7,45 (d, 2H), 7,20 (DD, 1H), 2,03 (s, 3H)
N-[3-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)phenyl]benzamideAnd3310,22,77 (A)DMSO(d6): 9,86 (s, 1H, NH), 9,13 (s, 1H, NH), to 8.41 (DD, 1H), 7,99 (m, 2H), to 7.84 (d, 1H), to 7.75 (m, 2H, NH2), from 7.24 (d, 1H), 7,22 (DD, 1H), 7,13 (t, 1H), to 7.09 (d, 1H), 2,07 (s, 3H, CHC)
1-(2-Chlorophenyl)-N3-(3,4-acid)-1H-[1,2,4]triazole-3,5-diamineA*3346,22,90 (A)DMSO(d6): 8,55 (s, 1H), 7,65 (m, 1H), 7,53 (m, 1H), 7,49 (m, 2H), 7,17 (d, 1H), 7,07 (DD, 1H), 6,78 (d, 1H), 6,20 (s, 2H), 3,68 (s, 3H), of 3.65 (s, 3H), CDCl3: 7,5 (m, 2H), and 7.4 (m, 2H), and 7.1 (d, 1H), 6,9 (DD, 1H), 6,7 (d, 1H), 6,6 (Sirs, 1H), and 3.8 (s, 3H), and 3.7 (s, 3H)
N3-[4-Methoxy-3-(2-methoxyethoxy)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3357,22,96DMSO(d6): 8,88 (s, 1H), to 8.41 (DD, 1H), 7,97 (TD, 1H), 7,68 (m, 3H), of 7.36 (d, 1H), 7,21 (DD, 1H), 7,18 (DD, 1H), 6.89 in (d, 1H), 4,08 (t, 2H), 3,71 (s, 3H), 3,70 (t, 2H), 3.33 and (s, 3H)
N3-[3-Methoxy-4-(2-methoxyethoxy)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3357,22,83DMSO(d6): 8,90 (s, 1H), to 8.41 (DD, 1H), 7,97 (TD, 1H), 7,68 (m, 3H), 7,40 (d, 1H), 7^1 (DD, 1H), 7,12 (DD, 1H), 6,86 (d, 1H), 3,99 (t, 2H), of 3.78 (s, 3H), 3,63 (t, 2H), 3,32 (s, 3H)
N3-[3,4-Bis-(2-methodology is setacci)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine And3401,22,90DMSO(d6): 8,91 (s, 1H), to 8.41 (DD, 1H), 7,98 (TD, 1H), 7,68 (m, 3H), 7,39 (d, 1H), 7,21 (DD, 1H), 7,14 (DD, 1H), 6.89 in (d, 1H), 4,11 (t, 2H), a 4.03 (t, 2H), 3,70 (t, 2H), 3,62 (t, 2H), 3,35 (s, 3H), 3,32 (s, 3H)
N3-Phenyl-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3253,13,21DMSO(d6): 9,12 (s, 1H), to 8.41 (DD, H), 7,98 (TD, 1H), of 7.70 (d, 1H), 7.68 per cm., s, 2H), 7,63 (d, 2H), 7,25 (m, 2H), 7,21 (DD, 1H), PC 6.82 (t, 1H),
N3-(3,5-Acid)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3313,13,19 (A)DMSO(d6): remaining 9.08 (s, 1H), to 8.41 (DD, H), of 8.00 (dt, 1H), of 7.70 (s, 2H), to 7.64 (d, 1H), 7.23 percent (DD, 1H), 6.90 to (d, 2H), 6,03 (t, 1H), 6.73 x (s, 6H)
1-Pyridin-2-yl-N3-(triptoreline)-1H-[1,2,4]triazole-3,5-diamineAnd3321,13,86DMSO(d6): 9,58 (s, 1H), 8,42 (DD, 1H), 8,03 (C, HP, 8,01 (TD, 1H), 7,87 (DD, 1H), of 7.70 (s, 2H), 7,66 (d, H), of 7.48 (t, 1H), 7.23 percent (DD, 1H), 7,15 (d, 1H),
N3-(4-Butoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3325,23,55 (A)DMSO(d6): 8,88 (s, 1H), 8,40 (DD, 1H), 7,97 (TD, 1H), to 7.67 (m, 3R), 7,52 (d, 2H), 7,17 (DD, 1H), for 6.81 (d, 2H), 3,90 (m, 2H), 1,67 (m, 2H), 1,42 (m, 2H), of 0.93 (t, 3H)
N3-[3,5-Differenl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3289,13,3 (A) DMSO(d6): 9,41 (s, 1H), 8,42 (DD, 1H), 8,00 (TD, 1H), to 7.75 (m, 3H), 7,68 (d, 1H), 7,30 (m, 2H), 7.23 percent (DD, 1H)
1-(2-Forfinal)-N3-(3,4,5-trimethoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineS*3360,12,97 (A)1H-DMSO(d6): 8,71 (s, 1H), 7,56 (TD, 1H), 7,46 (m, 1H), 7,41 (TD, 1H), 7,32 (TD, 1H), 6,92 (s, 2H), 6,34 (s, 2H), 3,68 (s, 6H), 3,55 (s, 3H)
4-[5-Amino-3-(3,4,5-trimethoxybenzylamine)-[1,2,4]triazole-1-yl]benzonitrileS*3367,2is 3.08 (A)1H-DMSO(d6): of 8.95 (s, 1H), 7,94 (d, 2H), 7,80 (d, 2H), 7,00 (s, 2H), 6,80 (s, 2H), 3,82 (s, 6H), of 3.56 (s, 3H)
4-[3-Amino-3-(3,4,5-trimethoxybenzylamine)-[1,2,4]triazole-1-yl]benzonitrileS*3367,22,83 (A)H-DMSO(d6): of 8.95 (s, 1H), 7,94 (d, 2H), 7,73 (d, 2H), 6,85 (s, 2H), ceiling of 5.60 (s, 2H), of 3.73 (s, 6H), of 3.60 (s, 3H)
N3-(4-Chloro-2,5-acid)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3347,13,57 (A)DMSO(d6): 8,44 (DDD, 1H), 8,17 (s, 1H), 8,01 (TD, 1H), 7,88 (width, s, 2H, NH2), of 7.70 (s, 1H), 7,68 (d, 1H), 7,25 (DDD, 1H), was 7.08 (s, 1H), 3,90 (s, 3H), 3,83 (s, 3H)
N3-(5-Chloro-2-methoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3313,13,34DMSO(d6): to 8.45 (DD, 1H), they were 8.22 (d, 1H), with 8.05 (dt, 1H), 7,97 (m, 2H), 7,81 (s, 1H), 7,66 (d, 1H), 7,28 (DD, 1H), 7,00 (d, 1H), 6,92 (DD, 1H), with 3.89 (s, 3H)
And3325,23,53DMSO(d6): 11,17 (s, 1H), 9,85 (s, 1H), 8,49 (d, 1H), 8,42 (d, 1H), 7,98 (t, 1H), to 7.59 (d, 1H), 7,20 (m, 1H), 6,83 (d, 1H), 6,78 (d, 1H), 5,70 (width,s, 2H), 1.28 (in s, 9H)
N3-(2-Methoxy-5-nitrophenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3328,13,51DMSO(d6): 9,20 (d, 1H), 8,45 (d, 1H), 8,10 (s, 1H), of 8.06 (t, 1H), 7,87 (DD, 1H), 7,81 (s, 2H), 7,69 (d, 1H), 7,26 (t, 1H), 7,20 (m, 1H), 4.00 points (s, 3H)
Methyl ester 3-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-4-methoxybenzoic acidAnd3341,13,29DMSO(d6): 8,90 (d, 1H), 8,43 (d, 1H), with 8.05 (dt, 1H), 7,78 (s, 2H), 7,69 (d, 1H), to 7.64 (s, 1H), 7,55 (DD, 1H), 7,25 (DD, 1H), 7,11 (d, 1H), 3,92 (s, 3H), of 3.84 (s, 3H)
N3-(2-Methoxy-5-triptoreline)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3351,24,00DMSO(d6): 8,56 (d, 1H), 8,44 (d, 1H), with 8.05 (dt, 1H), 7,86 (s, 1H), to 7.84 (m, 2H), to 7.61 (d, 1H), 7,25 (d, 1H), 7,24 (d, 1H), 7,17 (DD, 1H), of 3.97 (s, 3H)
3-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]thiazol-3-ylamino)biphenyl-4-olAnd3345,13,47DMSO(d6): 11,30 (s, 1H), 10,32 (width,s, 1H), 8,66 (d, 1H), 8,45 (DD, 1H), 8,00 (TD, 1H), to 7.61 (d, 1H), EUR 7.57 (m, 2H), 7,45 (t, 2H), 7,30 (m, 1H), 7.23 percent (TD, 1H), 7,13 (DD, 1H), 6,98 (d, 1H), 5,80 (m, 2H)
1-Pyridin-2-yl-N3-(2,3,5-trimethoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd3343,13,21DMSO(d6): 8,46 (DD, 1H), 8,10 (m, 2H), 8,04 (TD, 1H), 7,95 (width,s, 1H), 7,69 (d, 1H), 7,53 (d, 1H), 7,28 (DD, 1H), and 6.25 (d, 1H), 3,82 (s, 3H), 3,79 (s, 3H), and 3.72 (s, 3H)
N3-(2,5-deformational)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine3289,13,70DMSO(d6): 9,03 (s, 1H), 8,43 (DD, 1H), 8,12 (DDD, 1H), 8,01 (TD, 1H), 7,80 (width,s, 2H), 7,68 (d, 1H), 7,25 (DD, 1H), 7,20 (DDD, 1H), 6,69 (m, 1H)
N3-(2-Methoxy-5-triptoreline)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3367,23,90 (A)DMSO(d6): 8,43 (DD, 1H), of 8.25 (d, 1H), 8,02 (TD, 1H), 7,85 (Sirs, 2H, NH2), 7,81 (s, 1H, NH), a 7.62 (d, 1H), 7,26 (DD, 1H), 7,06 (d, 1H), 6,85 (DD, 1H), 3,90 (s, 3H)
1-Pyridin-2-yl-N3-(2-trifloromethyl)-1H-[1,2,4]triazole-3,5-diamineAnd3337,103,90DMSO(d6): 8,63 (s, 1H), 8,42 (DD, 1H), 8,35 (DD, 1H), 8,00 (TD, 1H), 7,74 (width,s, 2H), 7,71 (d, 1H), 7,34 (TD, 1H), 7,31 (DD, 1H), 7.23 percent (DD, 1H), 6,98 (TD, 1H)
N3-(2-Isopropoxy-5-methoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine3341,13,82DMSO(d6): 8,43 (DD, 1H), 8,02 (TD, 1H), 7,86 (m, 2H, NH2), a 7.85 (d, 1H), to 7.67 (d, 1H), 7,33 (s, 1H), 7,25 (DD, 1H), 6,94 (d, 1H), 6.42 per (DD, 1H), 4,55 (m, 1H), 3,74 (s, 3H), 1.28 (in C H), of 1.26 (s, 3H)
N3-(2-fluoro-5-morpholine-4-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine3356,23,248,49 (m, 1H), 8,40 (d, 1H), 8,00 (TD, 1H), of 7.90 (DD, 1H), 7,76 (width,s, 2H), to 7.61 (d, 1H), 7,22 (DD, 1H), 7,05 (DD, 1H), 6,50 (m, 1H), 3,78 (m, 4H), to 3.09 (m, 4H)
4-[5-Amino-3-(3,5-diisopropylamino)-[1,2,4]triazole-1-yl]benzonitrileD*3393,24,00 (A)DMSO(d6): of 8.92 (s, 1H), 7,95 (d, 2H), 7,80 (d, 2H), 6,77 (s, 2H), 6,76 (m, 2H), 3,95 (s, 1H), 4,47 (m, 2H), 1,21 (s ,6H), 1,22 (s, 6H)
4-[5-Amino-3-(3,5-dimethoxyaniline)-[1,2,4]triazole-1-yl]benzonitrileD*3335,2 (M-1)3,11DMSO(d6): 9,00 (s, 1H), 7,94 (d, 2H), 7,79 (d, 2H), 6,83 (d, 2H), 6,77 (m, 2H), 6,00 (t, 1H), 3,70 (s, 6H)
3-[5-Amino-3-(3,4,5-trimethoxybenzylamine)-[1,2,4]triazole-1-yl]benzonitrileD*3365,2 (M-1)2,74DMSO(d6): 8,86 (s, 1H), 7,98 (m, 1H), 7,94 (dt, 1H), 7,72 (dt, 1H), 7,68 (t, 1H), 6,97 (s, 2H), 6.75 in (m, 2H, in), 3.75 (s, 6H), to 3.58 (s, 3H)
N-{3-Acetylamino-5-[5-amino-(4-cyanophenyl)-1H-[1,2,4]triazole-3-ylamino]phenyl}ndimethylacetamideC*3391,22,05DMSO(d6): 9,76 (s, 2H), 8,97 (s, 1H), to 7.93 (d, 2H), of 7.90 (d, 2H), 7,54 (s, 2H), 7,40 (s, 1H), of 6.71 (s, 2H), 2,02 (s, 6H)
4-[5-Amino-3-(3,5-dimethoxy-4-methylphenylimino)-[1,2,4]triazole-yl]benzonitrile D*3to 351.33,50DMSO(d6): of 8.92 (s, 1H), to 7.93 (d, 2H), 7,80 (d, 2H), 6,97 (s, 2H), 6.8 cm (width, s, 2H), 3,74 (s, 6H), 1.91 a (s, 3H),
N3-(3-methoxy-4-morpholine-4-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineD3368,31,79DMSO(d6): was 9.33 (Shir. s, 1H), 8,42 (DD, 1H), 8,00 (TD, 1H), to 7.77 (m, 2H), of 7.70 (d, 1H), to 7.61 (s, 1H), 7,32 (m, 1H), 7,22 (m, 2H), of 3.94 (s, 3H), 3,90 (m, 4H), to 3.38 (m, 4H)
4-[5-Amino-3-(3-methoxy-4-morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]benzonitrileD*3392,21,79DMSO(d6): 9,18 (Shir. s, 1H), 7,94 (d, 2H), 7,80 (d, 2H), 7,47 (s, 1H), 7,18 (width,s, 2H), for 6.81 (m, 2H), 3,78 (m, 7H), 3,90 (m, 4H), 3,20 (m, 4H)
N3-(3,5-Acid)1-(2-forfinal)-1H-[1,2,4]triazole-3,5-diamineD*3386,33,90DMSO(d6): 8,73 (s, 1H), 7,54 (TD, H), of 7.48 (m, 1H), 7,40 (t, 1H), 7,32 (m, 1H), of 6.68 (d, 2H), 6.4 (m, 2H), 5,59 (m, 1H), 4,46 (m, 2H), 1,23 (s, 6H), to 1.21 (s, 6H)
N3-(3-Isopropoxy-4-morpholine-4-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineD3396,32,42DMSO(d6): 9,27 (s, 1H, NH), 8,42 DD, 1H), 8,00 (TD, 1H), 7,73 (m, 2H, NH2), the 7.65 (d, 1H), 7,60 (s, 1H), 7,22 (m, 2H), 7,14 (d, 1H), 4,69 (m, 1H), 3,90 (m, 4H), to 3.38 (m, 4H), of 1.42 (d, 6H)
4-[5-Amino-3-(3-isopropoxy-4-morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]benzonitrile D*3420,32,31DMSO(d6): 9,20 (s, 1H, NH), of 7.96 (d, 2H), 7,80 (d, 2H), 7,54 (s, 1H), 7,20 (m, 1H), 7,11 (DD, 1H), PC 6.82 (m, 2H), with 4.64 (m, 1H), 3,88 (m, 4H), to 3.34 (m, 4H), to 1.38 (d, 6H)
N3-(3-Isopropoxy-4-morpholine-4-ylmethylene)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineD3410,33,00 (A)DMSO(d6): 9,36 (s, 1H, NH), 8,42 (DD, 1H), 8,00 (TD, 1H), of 7.70 (m, 2H, NH2), the 7.65 (d, 1H), 7.62mm (d, 1H), 7,30 (d, 1H), 7.23 percent (DD, 1H), 7,12 (DD, 1H), 4,63 (m, 1H), 4,20 (s, 2H), 3,97 (d, 2H), the 3.65 (t, 2H), of 3.31 (d, 2H), 3,10 (m, 2H), 1,41 (s, 3H), 1,40 (,
4-[5-Amino-3-(3-isopropoxy-4-morpholine-4-iletilenlerin)-[1,2,4]triazole-1-yl]benzonitrileD*3434,33,02DMSO(6): of 9.30 (s, 1H), 7,95 (d, 2H), 7,79 (d, 2H), 7,58 (d, 1H), 7,28 (d, 1H), was 7.08 (DD, 1H), 6,80 (width, s, 2H, NH2), 4,60 (m, 1H), 4,18 (d, 2H), 3.96 points (d, 2H), to 3.64 (t, 2H), 7,30 (m, 2H), 3,10 (square, 2H), to 1.38 (d, 6H)

4-[5-Amino-3-(2,4-dimethoxyaniline)-[1,2,4]triazole-1-yl]benzonitrileA*1337,003,18DMSO: 7,9 (m, 3H), and 7.8 (d, 2H), and 7.1 (s, 1H), 6,8 (s, 2H), and 6.6 (s, 1H), 6,5 (d, 1H), 3,9 (s, 3H), and 3.7 (s, 3H)
4-[3-Amino-5-(2-chlorpheniramine)-[1,2,4]triazole-1-yl]benzonitrileA*1311,003.04 fromDMSO: 8,7 (s, 1H), 8.0 a (d, 2H), and 7.8 (d, 2H), and 7.6 (d, 1H), and 7.4 (d, 1H), and 7.3 (t, 1H), and 7.1 (t, 1H), 5,7 (Sirs, 2H),
4-[3-Amino-5-(4-(morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]benzonitrileA*2362,202,01DMSO: 8,8 (s ,1H), 7,9 (d, 2H), and 7.8 (d, 2H), and 7.3 (d, 2H), 6,9 (d, 2H), 5,6 (s, 2H), and 3.7 (m, 4H), 3.0 a (m, 4H)
4-[5-Amino-3-[3-methoxy-4-(3-piperidine-1-ylpropionic)phenylamino]-[1,2,4]triazole-1-yl]benzonitrileA*3448,301,88acetone-d6: 10,1 (Sirs, 1H), 9,1 (Sirs, 1H), 7,9 (Sirs, 4H), to 7.4 (m, 3H), and 7.1 (d, 1H), 6,9 (d, 1H), 4,2 (m, 2H), 3,9 (s, 3H), and 3.8 (m, 2H), 3,1 (m, 2H), 2,3 (m, 2H), 2,0-1,8 (m, 5H), 1,6 (m, 1H)
N3-(2,4-Acid)1-[4-(1H-tetrazol-5-yl)phenyl]-1H-[1,2,4]triazole-3,5-diamine3380,202,61acetone-d6: 8,3 (d, 2H)and 8.1 (d, 1H), 7,9 (d, 2H), 7,3 (Sirs, 1H), 6,7 (Sirs, 2H), and 6.6 (m, 1H), 6,5 (DD, 1H) x 3.9 (s, 3H), and 3.8 (s, 3H)
4-[5-Amino-3-(2,5-dimethoxyaniline)-[1,2,4]triazole-1-yl]bentonite the A*3337,003,35DMSO-d6: 8,0 (d, 2H), and 7.8 (m, 3H), and 7.3 (s, 1H), 6.90 to (d, 1H), 6,85 (s, 2H), 6,4 (DD, 1H), and 3.8 (s, 3H), and 3.7 (s, 3H)
4-[3-Amino-5-(2,5-dimethoxyaniline)-[1,2,4]triazole-1-yl]benzonitrile2337,003,06DMSO-d6: 8,1 (s, 1H), 8.0 a (d, 2H), and 7.8 (d, 2H),and 7.5 (s, 1H), 6,9 (d, 1H), 6,5 (DD, 1H), 5,6 (Sirs, 2H), and 3.8 (s, 3H), and 3.7 (s, 3H)
N3-(2,5-Dimethoxy-4-pyridin-4-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineA*2390,302,13DMSO-d6: 8,55 (d, 2H), 8,45 (m, 1H), to 8.20 (s, 1H), 8.0 a (t, 1H), 7,8 (Sirs, 2H), of 7.75 (d, 1H), of 7.70 (s, 1H), 7,60 (m, 2H), 7,25 (m, 1H), 7,07 (Sirs, 1H), 3,90 (s, 3H), 3,85 (3, 3H)
N3-[3,4-Dimethoxy-5-(3-morpholine-4-ylpropionic)phenyl}-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineA*2456,301,89CDCl3: 8,30 (m, 1H), 7,8 (m, 1H), 7.7 (d, 1H), 7,05 (m, 1H), 6,8 (d, 1H), 6.75 in (s, 1H), 6,70 (Sirs, 2H), and 6.6 (s,1H), 4,1 (t, 2H), 3,85 (s, 3H), of 3.75 (s, 3H), 3,70 (m, 4H), and 2.6 (m, 2H), 2,3 (m, 4H), 2.05 is (m, 2H),
N3-[3-(3-Dimethylaminopropoxy)-4,5-acid]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineA*2414,201,93CDCl3: 8,3 (m, 1H), to 7.75 (m, 1H), 7,65 (d, 1H), 7,0 (m, 1H), 6,80 (m, 1H), 6.75 in (Sirs, 2H), 6.75 in (m, 1H), 4,0 (t, 2H), and 3.8 (s, 3H), and 3.7 (s, 3H), by 2.55 (t, 2H, in), 2.25 (s, 6H), 2.0 (m, 2H)
4-[amino-3-[3-(2-dimethylaminoethoxy)-4,5-dimethoxyaniline]-[1,2,4]triazole-1-yl]benzonitrile S*2424,201,84DMSO-d6: 9,0 (s, 1H), 8.0 a (d, 2H), and 7.8 (d, 2H), 7,05 (m, 1H), 7,0 (m, 1H), 6,8 (Sirs, 2H), 4,3 (t, 2H, in), 3.75 (s, 3H), of 3.65 (s, 3H), 3,5 (m, 2H), 2,9 (Sirs, 6H)
1-Pyridin-4-yl-N3-(3,4,5-trimethoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineIn2343,201,61DMSO-d6: 9,0 (s, 1H), and 8.6 (d, 2H), and 7.6 (d, 2H), 7,0 (s, 2H), 6,85 (Sirs, 2H, in), 3.75 (s, 6H), and 3.6 (s, 3H)
1-Pyridin-4-yl-N5-(3,4,5-trimethoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineIn2343,201,61DMSO-d6: 9,0 (s, 1H), and 8.6 (d, 2H), and 7.6 (d, 2H), 6,8 (s, 2H), 5,6 (Shir. s, 2H), and 3.7 (s, 6H), and 3.6 (s, 3H)
4-{5-Amino-3-[3,4-dimethoxy-5-(2-morpholine-4-ylethoxy)phenylamino]-[1,2,4]triazole-1-yl]benzonitrileS*2466,101,96
4-(5-Amino-3-{3-[2-(2,6-dimethylmorpholine-4-yl)ethoxy]-4,5-dimethoxyaniline}-[1,2,4]triazole-1-yl]benzonitrileAnd2493,302,10D0-d6: of 8.95 (s, 1H), 7,95 (d, 2H), 7,80 (d, 2H), 7,0 (d, 1H), 6,9 (d,1 H), 6.75 in (Sirs, 2H), of 4.05 (t, 1H, in), 3.75 (s, 3H), 3,6 (s, 3H), at 3.35 (m, 2H), 2,85 (d, 2H, in), 3.75 (t, 2H), 1,73 (t, 2H), of 1.05 (d, 6H),
4-(5-Amino-3-{3,4-dimethoxy-5-[2-(4-methylpiperazin-1-yl)ethoxyphenylurea}-[1,2,4]triazole-1-yl)benzonitrileA*2479,301,75 DMSO-d6: 9,0 (s, 1H), 7,95 (d, 2H), 7,80 (d, 2H), 7,0 (s, 2H), 6,8 (Sirs, 2H), 4,15 (m, 2H), of 4.05 (m, 2H, in), 3.75 (s, 3H), of 3.65 (s, 3H), 3.15 in (s, 3H), 2,8 (m, 4H), to 2.65 (m, 4H)
4-[5-Amino-3-(2-methoxy-4-morpholine-4-iletilenlerin)-[1,2,4]triazole-1-yl]benzonitrileA*3406,201,77DMSO-d6: 8,0 (d, 1H), 7,95 (d, 2H), and 7.8 (d, 2H), 7,25 (s, 1H), 6,9 (s, 1H), 6,8 (m, 3H), at 3.9 (s, 3H), 3,6 (m, 4H), 3,4 (s, 2H), 2,35(m, 4H)
4-{5-Amino-3-[2-methoxy-4-(4-methylpiperazin-1-methyl)phenylamino]-[1,2,4]triazole-1-yl}benzonitrileA*3419,30of 1.34DMSO-d6: 8,1 (d, 1H), 7,95 (d, 2H), and 7.8 (d, 2H), 7,55(Sirs, 1H), 7,05 (Sirs, 1H), 6,95 (d, 1H), 6,85 (Sirs, 2H), 3,9 (s, 3H), 2,8 (Sirs, 3H)
4-{5-Amino-3-[3-(2-imidazolyl-1 ylethoxy)-4,5-dimethoxyaniline]-[1,2,4]triazole-1-yl}benzonitrileA*2
4-{3-Amino-5-[3-(2-diethylaminoethoxy)-4,5-dimethoxyaniline]-[1,2,4]triazole-1-yl}benzonitrileA*3
N3-(2-Methoxy-4-morpholine-4-ylmethylene)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineIn*3382,201,70DMSO-d6: 8,4 (d, 1H)and 8.1 (d, 1H), 7,95 (m, 1H), and 7.7 (m, 3H), and 7.3 (s, 1H), 7,2 (m, 1H), 6,9 (s, 1H), 6,83 (d, 1H), 3,85 (s, 3H), 3,6 (m, 4H), 3,4 (s, 2H), 2,4(Sirs, 4H)
N3-[2-Methoxy-4-(4-methylpiperazin-1-ylmethyl)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineIn3395,201,30DMSO-d6: to 8.45 (d, 1H), of 8.25 (d, 1H), 8.0 a (m, 1H), 7,8 (Sirs, 2H), 7.7 (d, 1H), and 7.6 (s, 1H), 7,25 (m, 1H), and 7.1 (s, 1H), 7,0 (d, 1H), 4.2V (Sirs, 2H), 3,9 (s, 3H), 3,8-3,0 (ocsi. s, 8H), 2,85 (Sirs, 3H)
1-[6-(2-Diethylaminoethylamine)pyrimidine-4-yl]-N3-(2-methoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineIn2370,301,59CD3CN: and 8.4 (s, 1H), 8,2 (Sirs, 1H), 8.0 a (m, 1H), 7,8 (m, 1H), 6,9 (m, 4H), 6.75 in (s, 1H), 3,85 (s, 3H), and 3.7 (m, 2H), 3,25 (m, 2H), and 2.8 (s, 6H)
2-[5-(Amino-3-(2-forgenerating)-[1,2,4]triazole-1-yl]pyrimidine-5-carbonitrileIn1DMSO-d6: 9,2 (s, 2H), up 8.75 (s, 1H), and 8.2 (m, 1H), 7,9 (Sirs, 2H), 7,15 (m, 2H), 6,9 (m, 1H)
2-[5-(Amino-3-(2-methoxyphenylazo)-[1,2,4]triazole-1-yl]pyrimidine-5-carbonitrileIn1309,102,78DMSO-d6: 9,2 (s, 2H), and 8.2 (m, 1H), 7,9 (Sirs, 2H), and 7.5 (s, 1H), 7,0 (m, 3H), 3,85 (s, 3H)
N3-(2-Methoxyphenyl)-1-(6-morpholine-4-Yeremey-4-yl)-1H-[1,2,4]triazole-3,5-diamineG3369,203,30DMSO-d6: 8,5 (s, 1H)and 8.1 (d, 1H), 7,9 (Sirs, 2H), and 7.4 (Sirs, 1H), 7,0 to 6.8 (m, 3H), 6,8 (s, 1H), 3,9 (s, 3H), and 3.7 (m, 4H), 3,6 (m, 4H)
N3-(2-Methoxyphenyl)-1-[6-(4-methylpiperazin-1-yl)-pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineIn3382,201,70CDG3: 8,3 (s, 1H)and 8.1 (d, 1H), 7,05 (bc, 1H), 6,95 (t, 1H), 6,8 (m, 2H), 6.75 in (s, 1H), 6,65 (bc, 2H), 3,85 (s, 3H), 3,70 (m, 4H), of 2.45 (m, 4H), 2,3 (s, 3H)
N3-(2-Methoxy-4-morpholine-4-ylphenyl)-1-[6-(4-methylpiperazin-1-yl)pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineIn2467,201,50CDCB: 8,3 (s, 1H), 8.0 a (d, 1H), 6,85 (s, 1H), 6.75 in (s, 1H), 6,65 (Sirs, 2H), 6,5 (DD, 1H), 6,45 (m, 1H), and 3.8 (m, 7H), and 3.7 (m, 4H), 3,05 (m, 4H), of 2.45 (m, 4H), 2,3 (s, 3H), 1,5 (Sirs, 2H)
N3-(2-Methoxypropan-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineIn2291,100,30DMSO-d6: 11,1 (Sirs, 1H), 7,9 (d, 1H), and 6.6 (d, 1H), 6,4 (DD, 1H), 5,8 (Sirs, 2H), 3,85 (s, 3H), of 3.75 (m, 4H), 3.0 a (m, 4H)
1-{6-[(2-Dimethylaminoethyl)methylamino]pyrimidine-4-yl}-N3-(2-methoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineIn3384,201,90CD3CN: to 8.45 (s, 1H), 8.3 (Sirs, 2H), 8,15 (m, 1H), 7,9(Sirs, 1H), 7,05 (m, 3H), to 6.80 (m, 1H), 4,0 (m, 2H), 3,9 (s, 3H), at 3.35(m, 2H), 3.15 in (s, 3H), 2,9 (Sirs, 6H)
1-{6-[(2-Dimethylaminoethyl)methylamino]pyrimidine-4-yl}-N3-(2-methoxy-4-morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineIn2469,201,67
1-[6-(3-Dimethylaminopropan-1-yl]pyrimidine-4-yl]-N3-(2-methoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineIn2396,301,80DMSO: 8,4 (s, 1H)and 8.1 (s, 1H), 7,8 (Sirs, 2H), and 7.4 (s, 1H), 6,9 (m, 3H), 6,5 (s, 1H), 3,9 (s, 3H), and 3.7 (m, 1H), 3,4 (m, 1H), 3,2 (m, 2H), 2,8 (m, 1H), 2,2 (Sirs, 6H), and 1.9 (m, 1H)
1-[6-(2-Diethylaminoethylamine)pyrimidine-4-yl]-N3-phenyl-1H-[1,2,4]triazole-3,5-diamineG3340,201,80MeOH-d4: 8,4 (s, 1H), 7.5 (d, 2H) to 7.2 (m, 2H), 6,9 (m, 1H), 6,8 (s, 1H), and 3.8 (m, 2H), 3,4 (m, 2H), 3.0 a (s, 6H)

N3-Benzo[1,3]dioxol-5-yl-1-pyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamineG1354,201,39DMSO-d6: 11,4 (Sirs, 1H), up 8.75 (s, 1H), 7,45 (m, 3H), 6,85 (d, 2H), 6,7 (Sirs, 2H), and 6.6 (d, 1H), 6,4 (s, 1H) 3,75 (m, 4H), 2.95 and (m, 4H)
1-[6-(2-Diethylaminoethylamine)-pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine2425,200,30DMSO-d6: 8,8 (s, 1H), and 8.3 (s, 1H), 7,65 (Sirs, 2H), 7.5 (d, 2H), 6,85 (d, 2H), 6,65 (Sirs, 1H), and 3.7 (m, 4H), 3,4 (Sirs, 2H), 3.0 a (m, 4H), 2,4 (m, 2H), 2,2 (Sirs, 6H),
1-[6-(2-Diethylaminoethylamine)-pyrimidine-4-yl]-N5-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine2425,20 0,30DMSO-d6: 8,4 (Sirs, 1H), 7,55 (m, 3H), 6,95 (d, 2H), 6,5 (Sirs, 1H), 5,7 (Sirs, 2H, in), 3.75 (m, 4H), 3,3 (Sirs, 2H), 3,05 (m, 4H), 2,4 (m, 2H), 2,2 (s, 6H)
N3-(4-(Morpholine-4-ylphenyl)-1-pyrimidine-4-yl-1H-[1,2,4]triazole-3,5-diamine2339,401,60DMSO-d6: of 8.95 (s, 1H), of 8.90 (s, 1H), 7,8 (Sirs, 2H), and 7.6 (s, 1H), 7.5 (d, 2H), 6,9 (d, 2H, in), 3.75 (m, 4H), 3.0 a (m, 4H)
N3-(4-phenylboronic acid)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine1297,002,30DMSO-d6: 9,3 (Sirs, 1H), and 8.4 (m, 1H), 8.0 a (m, 1H), and 7.7 (m, 3H), 7,55 (m, 2H), 7,2 (m, 1H)
1-[2-(2-Diethylaminoethylamine)-pyridin-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine2424,300,88CD3CN: is 7.9 (d, 1H), 7.5 (d, 2H), and 7.1 (m, 3H), at 3.9 (m, 4H), of 3.75 (m, 2H), 3,25 (m, 2H), 3,2 (m, 4H), and 2.8 (s, 6H)
1-[2-(4-Methylpiperazin-1-yl)pyridine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine2426,200,50DMSO-d6: 9,8 (Sirs, 1H), cent to 8.85 (Sirs, 1H), and 8.2 (d, 1H), 7.5 (d, 2H), 7,0(d, 1H), 6,95 (s, 1H), 6.90 to (m, 2H), 6,7 (Sirs, 2H), 4,45 (m, 2H, in), 3.75 (m, 4H), 3,5 (m, 2H), 3,2-3,0 (m, 8H), 2,85 (s, 3H)
N3-(3-Isopropoxy-4-morpholine-4-ylphenyl-1-[2-(4-methylpiperazin-1-yl]-pyridine-4-yl]-1H-[1,2,4]triazole-3,5-diamine2 494,402,68DMSO-d6: is 8.75 (s, 1H), 8,10 (d, 1H), 40 (s, 1H), 6,95 (d, 1H), 6.90 to (d, 1H), 6,85 (s, 1H), 6.75 in (d, 1H), 6,60 (Sirs, 2H), 4,50 (m, 1H), 3,70 (m, 4H), to 3.50 (m, 4H), 2,90 (m, 4H), 2.40 a (m, 4H), 2,22 (s, 3H), to 1.32 (d, 6H)
N5-Benzo[1,3]dioxol-5-yl-1-[2-(4-methylpiperazin-1-yl)pyridine-4-yl]-1H-[1,2,4]triazole-3,5-diamine2395,201,50CD3CN: 8,1 (d, 1H), 7,2 (s, 1H), 7,0 (s, 1H), 6,8 (d, 1H), 6,7 (m, 2H), of 6.65 (d, 1H), 5,7 (s, 2H), 5,2 (Sirs, 2H), 3,5 (m, 4H), 3,2 (s, 3H), 2,4 (m, 4H)
2-{[4-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)phenyl]-ethylamino}ethanol2340,102,10DMSO-d6: 8,55 (Sirs, 1H), scored 8.38 (m, 1H), 7,95 (m, 1H), 7,65 (m, 1H), 7,56 (m, 2H), 7,43 (m, 2H), 7,17 (m, 1H), 6,65 (m, 2H), 4,57 (t, 1H), 3,51 (m, 2H), 3,30 (m, 4H), was 1.04 (t, 3H)
N3-Methyl-N3-(4-(morpholine-4-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine2352,202,50DMSO-d6: of 8.37 (m, 1H), to $ 7.91 (m, 1H), 7,58 (m, 3H), 7,30 (m, 2H), 7,16 (m, 1H), 6,91 (d, 2H, in), 3.75 (m, 4H), to 3.35 (s, 3H), 3,05 (m, 4H)
-[6-(4-Ethylpiperazin-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineG1451,401,64DMSO-d6: 8,84 (s, 1H), of 8.37 (s, 1H), 7,72 (Sirs, 2H), of 7.48 (d, 2H), to 6.88 (d, 2H), 6,70 (s, 1H), to 3.73 (m, 4H), to 3.64 (m, 4H), to 3.00 (m, 4H), of 2.45 (t, 4H), 2,37 (square, 2H), was 1.04 (t, 3H)
1-[6-(3-Mailpipe Azin-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine 2437,330,31DMSO-d6: 8,82 (s, 1H), 8,35 (s, 1H), 7,71 (Sirs, 2H), 7,47 (d, 2H), 6.87 in (d, 2H), of 6.68 (s, 1H), 4,25 (m, 1H), 4,15 (m, 1H), and 3.72 (m, 4H), of 2.97 (m, 5H), 2,89 (t, 1H), to 2.67 (m, 2H), 2,53m, 1H), 2,34 (m, 1H), was 1.04 (d, 3H)
1-[6-(3-Dimethylaminopropan-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine2451,400,80DMSO-d6: 8,82 (s, 1H), 8.34 per (s, lH), of 7.70 (s, 2H), 7,49 (d, 2H), 6.87 in (d, 2H), to 6.39 (s, 1H), 3,71 (m, 4H), 2,99 (m, 4H), 2.49 USD (C, 7H), 1,86 (Sirs, 1H), 3,9-2,6 (5H)
1-[6-(4-Methyl[1,4]diazepan-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine2451,400,91CD3CN: to 8.41 (s, 1H), 7,94 (Sirs, (2H), a 7.62 (d, 2H) of 7.36 (d, 2H), 6,79 (s, lH), of 3.94 (m, 4H), 3,8-3,4 (m, 6H), to 3.36 (m, 4H), 3,17 (m, 2H), 2,82 (s, 3H), is 2.37 (m, 1H), and 2.26 (m, 1H)
1-{6-[2-Diethylaminoethyl)methylamino]pyrimidine-4-yl}-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine2467,201,46CD3CN: of 8.25 (s, 1H), 7,43 (d, 2H), 6,83 (m, 3H0, 6,64 (Sirs, lH), 3,66 (m, 4H), of 3.57 (m, 2H), is 3.08 (s, 3H), 2,98 (m, 4H), 2,6-2,4 (m, 6H), of 0.95 (t, 6H)
1-[6-(4-Isopropylpiperazine-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine1465,200,30DMSO-d6: cent to 8.85 (s, 1H), at 8.36 (s, 1H), 7,72 (W is D.C, 2H), 7,45 (d, 2H), 6,85 (d, 2H), 6,72 (s, 1H, in), 3.75 (m, 4H), 3, 65 (m, 4H), 3,05 (m, 4H), of 2.72 (m, 1H), 2,50 (m, 4H), and 1.00 (d, 6H)
1-[6-(4-Methylpiperazin-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineG2437,201,50DMSO-d6: 9,9 (Sirs, 1H), 8,9 (s, 1H), and 8.4 (s, 1H), 7,75 (Sirs, 2H), 7.5 (d, 2H), 6,9 (d, 2H), 6,8 (s, 1H), 4,5 (m, 2H, in), 3.75 (4H), 3,5 (m, 2H), 3,3 (m, 2H), 3,1 (m, 6H), and 2.8 (s, 3H)
1-[6-(2-Diethylaminoethylamine)-pyrimidine-4-yl]-N3-(2-forfinal)-1H-[1,2,4]triazole-3,5-diamineG3357,203,26DMSO-d6, and 8.6 (s, 1H), 8,45 (s, 1H), 8,15 (m, 1H), 7,8 (Sirs, 2H), 7,15 (m, 2H), 6,9 (m, 1H), 6.75 in (s, 1H), 3,75 (m, 4H), of 3.65 (m, 4H)

N3-Cyclohexyl-N3-(3,4,5-trimethoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineA*3348,202,45NMR performed in methanol-d4: 6,83 (s, 2H), of 4.05 (m, 1H), 3,85 (s, 6H), 3,71 (s, 3H), 1,98-1,71 (m, 3H), of 1.47 (m, 2H), 1.27mm (m, 1H)
1-(6-Methyl-4-triptorelin-2-yl)-N3-(3,4,5-trimethoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd1424,903,91NMR performed in DMSO-d6: 9,12 (s, 1H), 7,76 (s, 2H),,7,68 (s, 1H), 7,46 (s, 1H), was 7.08 (s, 2H), 3,80 (s, 6H), of 3.60 (s, 3H), 2,62 (s, 3H)
1-(4,6-Dimethylpyridin-2-yl)-N3-(3,4,5-trimethoxyphenyl)-1H-[1,2,4]triazo is for 3,5-diamine And1373,102,27NMR performed in DMSO-d6: 9,12 (s, 1H), 7,87 (s, 2H), 7,27 (s, 1H), 7,05 (s, 2H), 3,80 (s, 6H), of 3.60 (s, 3H), 2,60 (s, 3H), of 2.45 (s, 3H)
1-(4-Methylthiazole-2-yl)-N3-(3,4,5-trimethoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd1363,103,09NMR performed in DMSO-d6: 9,20 (s, 1H), 7,55 (s, 2H),,7,03 (s, 2H), 6,95 (s, 1H), of 3.78 (s, 6H), 3,61 (s, 3H), of 2.34 (s, 3H)
N3-(4-Dimethylaminophenyl)-1-(2,6-dimethylpyrimidin-4-yl)-1H-1,2,4]triazole-3,5-diamineAnd3325,02,673DMSO-d6: 8,80 (s, 1H), 7,80 (s, 2H), of 7.48 (d, 2H), 7,29 (s, 1H), of 6.71 (d, 2H), 2,80 (s, 6H), 2.57 m (s, 3H), of 2.45 (s, 3H)
N3-(4-piperidine-1-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3336,101,59DMSO-d6: 8,80 (s, 1H), 8,40 (d, 1H), 7,98 (t, 1H), to 7.67 (m, 3H), of 7.48 (m, 2H), 7,19 (t, 1H), 6,85 (m, 2H), 3,00 (m, 4H), to 1.61 (m, 4H), for 1.49 (m, 2H)
N3-(4-Isopropoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1311,103,24DMSO-d6: 8,89 (s, 1H), to 8.41 (d, 1H), 7,97 (t, 1H), to 7.77 (m, 3H), 7,52 (m, 2H), 7,20 (m, 1H), 6,85 (m, 2H), 4,49 (m, 1H), 1,25 (d, 6H)
N3-(2,3-Dihydrobenzo[1,4]dioxin-6-yl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1311,102,73DMSO-d6: 8,90 (s, 1H), 8.0 a (d, 1H), 8,00 (t, 1H), 7,65 (m, 3H), 7,30 (d, 1H), 7,20 (m, 1H), 7,00 (m, 1H), 6.75 in (d, 1H), 4,20 (m, 4H)
N3-(3-Ethoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1297,103,18DMSO-d6: 9,10 (s, 1H), 8,42 (d, 1H), 8,00 (t, 1H), 7,66 (m, 3H), 7,30 (m, 1H), 7,20 (m, 1H), 7,13 (m, 2H), 6,40 (d, 1H), 4.00 points (m, 2H), 1,35 (m, 3H)
N3-(4-Diethylaminophenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3324,201,45DMSO-d6: 8,63 (s, 1H), scored 8.38 (d, 1H), 7,95 (t, 1H), to 7.67 (d, 1H), 7.62mm (s, 2H), 7,45 (m, 2H), 7,18 (t, 1H),,of 6.65 (m, 2H), 3,25 (m, 4H), of 1.05 (m, 6H)
4-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)benzonitrileAnd3278,102,95DMSO-d6: 9,86 (s, 1H), 8,44 (d, 1H), 8,01 (t, 1H), 7,82-of 7.69 (m, 7H), 7,25 (m, 1H)
N3-[4-(4-Methylpiperazin-1-yl)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1351,401,27DMSO-d6: 8,80 (s, 1H), 8,40 (d, 1H), 7,98 (t, 1H), 7,65 (m, 3H), 7,50 (d, 2H), 7,19 (t, 1H), 6,85 (d, 2H), 3,01 (m, 4H), of 2.45 (m, 4H), of 2.21 (s, 3H)
N3-(1H-Indazol-5-yl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1293,102,12DMSO-d6: 12,82 (s, 1H), 9,07 (s, 1H), to 8.41 (d, 1H), 8,15 (s, 1H), 7,99 (m, 2H), 7,78 (d, 1H), of 7.70 (s, 2H), 7,45 (m, 2H), 7.23 percent (t, 1H)
1-[7-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-2,3-dihydr is indol-1-yl]alanon And1336,102,55DMSO-d6: 9,05 (s, 1H), to 8.57 (s, 1H), to 8.41 (d, 1H), 7,98 (t, 1H), 7,80 (d, 1H), 7,65 (s, 2H), 7,25 (d, 1H), 7,21 (t, 1H), 7,07 (d, 1H), 4.09 to (t, 2H), 3,05 (t, 2H), 2,18 (s, 3H)
N3-(4-Ethoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1297,103,09DMSO-d6: 8,90 (s, 1H), 8,40 (d, 1H), 7,98 (t, 1H), to 7.67 (m, 3H), 7,55 (m, 2H), 7,20 (m, 1H), 6,85 (m, 2H), 3.96 points (square, 2H), 1,31 (t, 3H)
N3-(4-Chloro-3-were)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1301,103,96DMSO-d6: 9,23 (s, 1H), to 8.41 (d, 1H), 7,99 (t, 1H), 7,71 (m, 3H), 7,55 (s, 1H), 7,50 (d, 1H), 7,25 (d, 1H), 7,20 (m, 1H), 2,31 (s, 3H)
N3-(4-Ethylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1281,303,51MeOH-d4: scored 8.38 (d, 1H), of 7.90 (t, 1H), of 7.75 (d, 1H), of 7.48 (d, 2H), 7,15 (t, 1H), 7,10 (d, 2H), 2,59 (square, 2H), 1,20 (t, 3H)
5-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-2-methoxyphenolAnd3299,10of 2.21MEOH-d4: to 8.40 (d, 1H), 7,98 (t, 1H), a 7.85 (d, 1H), 7,25 (m, 2H), 6.90 to (m, 2H), 3,82 (s, 3H)
N3-(3-Chloro-4-morpholine-4-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1372,103,47DMSO-d6: of 9.21 (s, 1H), 8,42 (d, 1H), 8,00 (t, 1H), to 7.75 (m, 3H), to 7.67 (d, 1H), 7,53 (d, 1H), 7,24 (t, 1H), and 13 (d, 1H), and 3.72 (m, 4H), 2,90 (m, 4H)
1-Pyridin-2-yl-N3-(3,4,5-trioxifene)-1H-[1,2,4]triazole-3,5-diamineAnd1385,203,74DMSO-d6: 8,91 (s, 1H), to 8.41 (d, 1H), 7,99 (t, 1H), 7,69 (s, 2H), a 7.62 (d, 1H), 7,21 (t, 1H), 7,05 (s, 2H), of 4.05 (m, 4H), 3,86 (m, 2H), of 1.35 (m, 6H), 1,22 (m, 3H)
N3-(3,4-Dioxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1341,103,37DMSO-d6: 8,86 (s, 1H), 8,40 (d, 1H), 7,99 (t, 1H), 7,65 (m, 3H), 7,35 (s, 1H), 7,20 (m, 1H), 7,12 (d, 1H), 6,85 (d, 1H), 4.04 the (square, 2H), 3,95 (square, 2H), to 1.38 (t, 3H), of 1.29 (t, 3H)
N3-(3-Chloro-4-diethylaminophenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3358,101,70Methanol-d4: 8,44 (d, 1H), 8,07 (s, 1H), 7,95 (t, 1H), to 7.75 (m, 2H), 7,65 (m, 1H), 7.23 percent (t, 1H), 3,70 (m, 4H)and 1.15 (m, 6H)
N3-[3-Methoxy-4-(3-piperidine-1-ylpropionic)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3424,201,76Methanol-d4: to 8.45 (d, 1H), 7,99 (t, 1H), 7,78 (d, 1H), 7,35 (s, 1H), 7,28 (m, 1H), 7,10 (m, 1H), 6,95 (d, 1H), 4,12 (m, 2H), 3,91 (s, 3H), to 3.67 (d, 2H), 3,38 (t, 2H), 2,99 (t, 2H, in), 2.25 (m, 2H), 2,00 (m, 2H,), of 1.85 (m, 3H), of 1.55 (m, lH)
N3-(2-Ethoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1297,103,70DMSO-d6: 8,42 (d, 1H), 8,19 (d, 1H), 7,99 (t, 1H), 7,72 (m, 3H), 7,25 (m, 2H), 6,95 (m, 2H), 6,85 (t, 1H), 4,13 (kV,2H), of 1.43 (t, 3H)
N3-(2-Fluoro-4-were)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1285,103,70DMSO-d6: 8,43 (m, 2H), with 8.05 (t, 1H), 7,98 (t, 1H), of 7.70 (m, 3H), of 7.23 (t, 1H), 7,01 (d, 1H), 6,95 (d, 1H), 2,28 (s, 3H)
N3-(2-Chloro-4-were)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1301,104,01DMSO-d6:8,42 (d, 1H), 8,10 (d, 1H), 7,98 (t, 1H), 7,73 (s, 2H), 7,68 (m, 2H), 7,25 (s, 1H), 7,22 (m, lH), to 7.15 (d, lH), and 2.27 (s, 3H)
N3-(3-methylbiphenyl-4-yl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1343,104,30DMSO-d6: 8,42 (d, 1H), 8,10 (d, 1H), 7,99 (m, 2H), 7,66 (m, 5H), was 7.45 (m, 4H), 7,30 (m, 1H), 7,22 (m, lH), of 2.38 (s, 3H)
N3-(N-Fluoren-1-yl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1341,104.26 deathsDMSO-d6: 8,61 (s, 1H), 8,45 (d, 1H), 8,10 (d, 1H), 7,99 (t, 1H), 7,86 (d, 1H), 7,71 (m, 3H), 7,60 (d, 1H), 7,50 (d, 1H), 7,38 (m, 2H), 7,33 (t, 1H), 7.23 percent (t, 1H), 3,97 (s, 2H)
N3-(4-Chloro-2-forfinal)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1305,003,90DMSO-d6: 8,89 (s, 1H), 8,43 (d, 1H), 8,28 (t, 1H), 8,00 (t, 1H), 7,80 (s, 2H), of 7.70 (d, 1H), 7,39 (d, 1H), 7,24 (m, 2H)
N3-(4-Chloro-2-were)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1301,00 3,92DMSO-d6: 8,42 (d, 1H), 8,03 (s, H), to 7.99 (m, 2H), 7,78 (s, 2H), 7,65 (d, 1H), 7,21 (m, 3H), of 2.28 (s, 3H)
N3-(2,4-Differenl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1289,003,50DMSO-d6: 8,68 (s, 1H), to 8.41 (d, H), 8,18 (m, 1H), 7,97 (t, 1H), to 7.77 (s, 2H), to 7.67 (d, 1H), 7,25 (m, 2H), 7,05 (t, 1H)
N3-(2-Chlorophenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3287,103,72DMSO-d6: 8,43 (d, 1H), 8,27 (d, H), to 7.99 (t, 1H), 7,81 (m, 3H), 7,71 (d, 1H), 7,45 (d, 1H), 7,35 (m, 1H), 7,25 (m, 1H), 6,95 (t, 1H)
N3-(4-isopropylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3295,203,98DMSO-d6: 9,05 (s, 1H), 8,43 (d, 1H), 7,99 (t, 1H), 7,80 (s, 2H), of 7.70 (d, 1H), 7,53 (d, 2H), 7,22 (m, 1H), 7,13 (d, 2H), 2,82 (m, 1H), 1,20 (d, 6H)
N3-(3-fluoro-2-methoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3301,103,60DMSO-d6: 8,43 (d, 1H), 8,07 (d, 1H), 8,00 (m, 2H), 7,74 (m, 3H), 7,25 (m, 1H), was 7.08 (m, 1H), 6,77 (t, 1H), with 3.89 (s, 3H)
N3-(2-Ethylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3281,203,55DMSO-d6: to 8.41(d, 1H), 7,95 (m, 2H), a 7.85 (s, 1H), 7,65 (m, 3H), 7,19 (m, 3H), 6,92 (t, 1H), 2,71 (square, 2H)and 1.15 (t, 3H)
N3-(2-Forfinal)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine 3271,203,35DMSO-d6: at 8.60 (s, 1H), 8,42 (d, 1H), 8,25 (t, 1H), 7,99 (t, 1H), 7,73 (m, 3H), from 7.24 (t, 1H), 7,15 (m, 2H), 6.90 to (m, 1H)
N3-(2-Methoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3283,203,35DMSO-d6: 8,42 (d, 1H), 8,21 (d, 1H), 7,99 (t, 1H), 7,74 (m, 3H), 7,35 (s, 1H), 7.23 percent (t, 1H), 6,97 (m, 2H), 6.89 in (t, 1H), 3,88 (s, 3H)
N3-(3-Ethoxy-4-methoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1327,103,00DMSO-d6: cent to 8.85 (s, 1H), to 8.41 (d, 1H), 7,99 (t, 1H), 7,65 (m, 3H), 7,35 (s,1H), 7,20 (m, 1H), 7,14 (d, 1H), 6,85 (d, 1H), was 4.02 (square, 2H), 3,70 (s, 3H), of 1.38 (t, 3H)
N3-(4-Chloro-2-methoxy-5-were)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1331,004,20DMSO-d6: 8,43 (d, 1H), 8,11 (s, 1H), 8,01(t, 1H), 7,94 (s, 2H), of 7.75 (d,1H), 7,60 (s,1H),125(t,1H), 7,05 (s, 1H), a 3.87 (s, 3H), 2,32 (s, 3H)
N3-(5-Chloro-2,4-acid)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1346,903,70DMSO-d6: 8,43 (d, 1H), 8,15 (s, 1H), 8,02 (t, 1H), 7,85 (s, 2H), to 7.64 (d, 1H), 7,51 (s, 1H), 7,25 (m, 1H), to 6.88 (s, 1H), 3,93 (s, 3H), 3,85 (s, 3H)
4-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-N-(2-diethylaminoethyl)benzamideAnd1395,301,80MeOH-d4: 8,43 (d, 1H), 7,9 (t, 1H), a 7.85 (m, 3H), of 7.70 (d, 2H), 7,25 (t, 1H, in), 3.75 (m, 2H), 3,39 (m, 2H), 3,32 (m, 4H), of 1.35 (m, 6H)
N3-[5-(1,1-Dimethylpropyl)-2-methoxyphenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1353,204,70DMSO-d6: 8,44 (d, 1H), of 8.25 (s, 1H), with 8.05 (t, 1H), 7,95 (s, 2H), 7,65 (d, 1H), 7,50 (s, 1H), 7,25 (m, 1H), 6,92 (d, 1H), 6,83 (d, 1H), 3,85 (s, 3H), 1,65 (square, 2H), 1,29 (s, 6H), 0.69 (t, 3H)
1-Pyridin-2-yl-N3-(2,3,4-trimethoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd3343,103,10DMSO-d6: 8,42 (d, 1H), 7,98 (t, 1H), to 7.84 (d, 1H), 7,79 (s, 2H), 7,69 (d, 1H), 7,58 (s, 1H), 7,22 (m, 1H), 6,78 (d, 1H), 3,85 (s, 3H), of 3.78 (s, 3H), 3,76 (s, 3H)
1-(2,4-Differenl)-N3-(3,4,5-trimethoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd3378,202,70DMSO-d6: 8,78 (s, 1H), to 7.64 (m, 1H), 7,51 (m, 1H), 7,24 (m, 1H), 6.90 to (s, 2H), 6,55 (s, 2H), 3,68 (s, 6H), 3,55 (s, 3H)
N3-(4-(Morpholine-4-ylphenyl)-1-phenyl-1H-[1,2,4]triazole-3,5-diamineAnd1337,301,80DMSO-d6: 8,61 (s, 1H), EUR 7.57 (d, 2H), 7,45 (m, 4H), 7,28 (m, 1H), at 6.84 (d, 2H), 6,38 (s, 2H), 3,71 (m, 4H), 2,98 (m, 4H)
1-(2-Forfinal)-N3-[3-methoxy-4-(3-piperidine-1-ylpropionic)phenyl]-1H-[1,2,4]triazole-3,5-diamineA*3441,201,70Methanol-d4: 7,63 (t, 1H), to 7.59 (m, 1H), 7,39 (m, 2H), 7,21 (s, 1H), 6,99 (d, 1H), 6.90 to (d, 1H), 4.09 to (t, 2H), 3,83 (s, 3H), of 3.65(d, 2H), the 3.35 (t, 2H), 2,96 (t, 2H), of 2.21 (m, 2H), 1,99 (m,2H), to 1.86 (m, 1H), 1,79 (m, 2H), 1.55V (m, 1H)
N3-(2,5-dioxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3341,204,00Methanol-d4: to 8.45 (d, 1H), 8,01 (t, 1H), 7,82 (m, 2H), 7,28 (m, 1H), 6,86 (d, 1H), 6,47 (d, 1H), of 4.05 (m, 4H), USD 1.43 (m, 6H)
N3-[3-Methoxy-4-(3-piperidine-1-ylpropionic)phenyl]-1-phenyl-1H-[1,2,4]triazole-3,5-diamineAnd3423,301,90Methanol-d4: to 7.59 (m, 4H), 7,47 (t, 1H), 7,27 (s, 1H), 7,03 (d, 1H), 6,92 (d, 1H), 4,1 (m, 2H), of 3.84 (s, 3H), of 3.65 (m, 2H), 3,35 (m, 2H), 2,96 (m, 2H), 2,22 (m, 2H), up to 1.98 (m, 2H), 1,89 of 1.50 (m, 4H)
N3-{4-[3-(2,6-Dimethylmorpholine-4-yl)propoxy]phenyl}-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3424,302,00MeOH-d4: 8,42 (d, 1H), 7,95 (t, 1H), 7,78 (d, 1H), 7-50 (d, 2H), 7,24 (t, 1H), 6,92 (d, 2H), 4,1 (m, 2H), 3,85 (m, 2H), 3,55 (d, 2H), 3,37 (m, 2H), 2,74 (t, 2H), 2,24 (m, 2H), 1,25 (d, 6H)
N3-[2-Morpholine-4-yl-4-(3-morpholine-4-ylpropionic)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3481,202,00DMSO-d6: 8,4 (d, 1H), with 8.05 (d, 1H), of 7.96 (t, 1H), of 7.70 (m, 3H), 7,37 (s, 1H), 7,21 (t, 1H), 6,79 (s, 1H), 6.75 in (d, 1H), 3,98 (t, 2H), 3,79 (m, 4H)and 3.59 (m, 4H), 2,82 (m, 4H), 2,4 (m, 6H), to 1.87 (m, 2H,)
N3-[4-(3-Morpholine-4-ylpropionic)phenyl]-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3396,20 1,80Methanol-d4: 8,42 (d, 1H), 7,95 (t, 1H), of 7.75 (d, 1H), 7,52 (d, 2H), 7.23 percent (t, 1H), 6,92 (d, 2H), 4,11 (m, 4H), 3,76 (t, 2H), only 3.57 (m, 2H), 3,40 (m, 2H), 3,23 (m, 2H, in), 2.25 (m, 2H)
4-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-N-[2-(3,5-dimethylpiperidin-1-yl)ethyl]benzamideAnd3435,202,20Methanol-d4: 8,43 (d, 1H), of 7.96 (t, 1H), to 7.84 (m, 3H), of 7.70 (d, 2H), 7,25 (m, 1H), of 3.77 (m, 2H), to 3.64 (m, 2H), 3,34 (m, 2H), has 2.56 (t, 2H), 1,95 (m, 3H) of 1.03 (d, 6H), of 0.93 (m, 1H)
N3-(4-Diethylaminophenyl)-1-phenyl-1H-[1,2,4]triazole-3,5-diamineAnd1323,001,40DMSO-d6: to 8.41 (s, 1H), EUR 7.57 (d, 2H), 7,49 (t, 2H), 7,40 (d, 2H), 7,26 (t, 1H), only 6.64 (d, 2H), 6.35mm (s, 2H), 3,24 (m, 4H), of 1.02 (t, 6H)
1-Phenyl-N3-(4-piperidine-1-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd1335,001,60DMSO-d6: 8,56 (s, 1H), 7,58 (d, 2H), 7,49 (t, 2H), 7,43 (d, 2H), 7,28 (m, 1H), PC 6.82 (d, 2H), 6,38 (s, 2H), 2,96 (m, 4H), of 1.62 (m, 4H), for 1.49 (m, 2H)
N3-(4-Isopropoxyphenyl)-1-phenyl-1H-[1,2,4]triazole-3,5-diamineAnd1310,103,20DMSO-d6: 8,67 (s, 1H), EUR 7.57 (d, 2H), of 7.48 (m, 4H), 7,29 (m, 1H), 6,80 (d, 2H), 6,40 (s, 2H), 4,46 (m, 1H), of 1.23 (d, 6H)
N3-(2,3-Dihydrobenzo[1,4]dioxin-6-yl)-1-phenyl-1H-[1,2,4]triazole-3,5-diamineAnd1310,102,70DMSO-d6: 8,68 (s, 1H), EUR 7.57 (d, 2H), 7,49 (t, 2H), 7,29 (m, 1H), and 7.4 (s, 1H), 6,92 (d, 1H), 6,80 (d, 1H), 6,41 (s, 2H), 4,15 (m, 4H)
N3-(3-Ethoxyphenyl)-1-phenyl-1H-[1,2,4]triazole-3,5-diamineAnd1296,103,20DMSO-d6: 8,90 (s, 1H), 7,58 (d, 2H), 7,50 (t, 2H), 7,30 (m, 1H), 7,25 (s, 1H), 7,07 (m, 2H), 6,45 (s, 2H), 6.35mm (m, 1H), 3,90 (square,2H), 1,32 (t, 3H)
N3-[4-(4-Methylpiperazin-1-yl)phenyl]-1-phenyl-1H-[1,2,4]triazole-3,5-diamineAnd3350,10,67DMSO-d6: 9,71 (Sirs, 1H), cent to 8.85 (s, 1H), 7,58 (d, 2H), 7,52 (d, 2H), of 7.48 (m, 2H), 7,32 (m, 1H), 6,92 (d, 2H), 6,68 (Sirs, 2H), 3,66 (m, 2H), 3,52 (m, 2H), 3,18 (m, 2H), 2,86 (m, 5H)
N3-(4-Ethoxyphenyl)-1-phenyl-1H-[1,2,4]triazole-3,5-diamineAnd1296,102,90DMSO-d6: 8,65 (s, 1H), 7,58 (d, 2H), of 7.48 (m, 4H), 7,29 (m, 1H), 6,80 (d, 2H), 6,40 (s, 2H), 3,95 (square, 2H), of 1.30 (t, 3H)

6-[5-Amino-3-(4-isopropoxyaniline)-[1,2,4]triazole-1-yl]nicotinamideB*3336,103,70DMSO-d6: 9,02 (s, 1H), 8,81 (s, 1H), at 8.36 (d, 1H), to 7.77 (m, 3H), 7,52 (d, 2H), 6,83 (d, 2H), 4,48 (m, 1H), 1.26 in (d, 6H)
4-[5-Amino-3-(7-methoxybenzo[1,3]dioxol-5-ylamino)-[1,2,4]triazole-1-yl]benzonitrileG*1351,203,10DMSO-d6: 8,91 (s, 1H), to 7.93 (d, 2H), 7,78 (d, 2H), 6,95 (s, 1H), 6.90 to (s, 1H), 6,74 (s, 2H), and 5.8 (s, 2H), 3,81 (s, 3H)
6-[5-Amino-3-(2-methoxyphenylazo)-[1,2,4]triazole-1-yl]nicotinamideIn*1308,103,50DMSO-d6: cent to 8.85 (s, 1H), scored 8.38 (d, 1H), 8,17 (d, 1H), 7,85 (s, 2H), 7,80 (d, 1H), 7,47 (s, 1H), 7.03 is-to 6.88 (m, 3H), 3,88 (s, 3H)
{4-[5-Amino-3-(2-methoxyphenylazo)-[1,2,4]triazole-1-yl]phenyl}morpholine-4-ylmethanolN3395,302,65Methanol-d4: with 8.05 (d, 1H), 7,73 (d, 2H), a 7.62 (d, 2H), 7,01-6,89 (m, 3H), of 3.95 (s, 3H), 3,82 is-3.45 (m, 8H)
{4-[5-Amino-3-(2-methoxyphenylazo)-[1,2,4]triazole-1-yl]phenyl}(4-methylpiperazin-1-yl)methanonN3408,301,66Methanol-d4: with 8.05 (d, 1H), 7,78 (d, 2H), to 7.67 (d, 2H), 7,01-6,89 (m, 3H), of 3.95 (s, 3H), 3,65 is 3.25 (m, 8H), 2.95 and (s, 3H)
4-[5-Amino-3-(2-methoxyphenylazo)-[1,2,4]triazole-1-yl]-N-methylbenzamideN3339,102,50Methanol-d4: with 8.05 (m, 3H), 7,73 (d, 2H), 7,05-6,93 (m, 3H), of 3.95 (s, 3H), 2.95 and (s, 3H),
4-(5-Amino-3-(2-methoxyphenylazo)-[1,2,4]triazole-1-yl]-N-(2-dimethylaminoethyl)-benzamideN3396,201,80Methanol-d4: with 8.05 (m, 3H), of 7.75 (d, 2H), 7,0-6,89 (m, 3H), 3,93 (s, 3H), of 3.78 (t, 2H), 3,4 (t, 2H), 3.0 a (s, 6H)
{4-[5-Amino-3-(2-methoxyphenylazo)-[1,2,4]triazole-1-yl]phenyl}piperidine-1-yl)methanonN 3393,203,20Methanol-d4: 8,0 (d, 1H), 7,72 (d, 2H), 7,58 (d, 2H), 7,02-6,89 (m, 3H), 3,93 (s, 3H), of 3.75 (m, 2H), 3.43 points (m, 2H), 1,78-of 1.55 (m, 6H)
6-[5-Amino-3-(2-forgenerating)-[1,2,4]triazole-1-yl]nicotinamideIn*1296,103,40DMSO-d6: cent to 8.85 (s, 1H), 8,73 (s, 1H), 8,40 (d, 1H), to 8.20 (t, 1H), 7,85 (s, 2H), 7,78 (d, 1H), 7,15 (m, 2H), 6,95 (m, 1H)
{4-[5-Amino-3-(2-methoxy-4-morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]phenyl}(4-methylpiperazin-1-yl)methanonN3493,402,10Methanol-d4: 8,07 (d, 1H), of 7.75 (d, 2H), 7,68 (d, 2H), 6,97 (m, 2H), 3,95 (m, 7H), of 3.45 (m, 6H), 3,44-of 3.25 (m,6H), 2.95 and (s, 3H)
{4-[5-Amino-3-(2-methoxy-4-morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]phenyl}morpholin-4-ylmethanoneN3480,402,00Methanol-d4: with 8.05 (d, 1H), 7,73 (d, 2H), a 7.62 (d, 2H), 6,95 (m, 2H), 3,95 (m, 7H), and 3.72 (m, 6H), 3,57-3,3 (m, 6H)
{4-[5-Amino-3-(2-methoxy-4-morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]phenyl}piperidine-1-ylmethanoneN3478,302,40Methanol-d4: with 8.05 (d, 1H), 7,71 (d, 2H), EUR 7.57 (d, 2H), 6,98 (t, 2H), 3,98 (t, 7H), 3,74 (t, 2H), 3,55-3,3 (m, 6H), about 1.75 to 1.5 (m, 6H)
4-[5-Amino-3-(2-methoxy-4-morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]-N-(2-dimethylaminoethyl)-benzamideN348130 1,10Methanol-d4: 8,05 (t, 3H), of 7.75 (d, 2H), 6,92 (t, 2H), 3,95 (m, 7H), 3,80 (t, 2H), 3,48-3,3 (t, 6N), 2,98 (s, 6H)
4-[5-Amino-3-(2-methoxy-4-morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]-N,N-dimethylbenzamideN3438,303,10Methanol-d4: 8,08 (d, 1H), 7,71 (d, 2H), 7,60 (d, 2H), 7,06 (s, 1H), 6,97 (d, 1H), 3,98 (t, 7H), of 3.48 (t, 4H), of 3.13 (s, 3H), 3.04 from (s, 3H)
6-[5-Amino-3-(benzo[1,3]dioxol-5-ylamino)[1,2,4]triazole-1-yl]nicotinamideD*1322,003,40DMSO-d6: 9,1 (s, 1H), and 8.8 (s, 1H), 8,35 (d, 1H), and 7.8 (s, 2H), 7,72 (d, 1H), and 7.3 (s, 1H), 7,05 (d, 1H), 6,8 (d, 1H), of 5.92 (s, 2H)
N3-(7-Methoxybenzo[1,3]dioxol-5-yl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineB*3327,003,30DMSO-d6: 8,86 (s, 1H), and 8.4 (d, 1H), 7,98 (t, 1H), 7,65 (t, 3H), 7,2 (t, 1H), 7,0 (s, 1H), 6,95 (s, 1H), 4,9 (s, 2H), of 3.84 (s, 3H)
1-(5-Methylpyridin-2-yl)-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineB1352,302,30DMSO-d6: a total of 8.74 (s, 1H), they were 8.22 (s, 1H), 7,78 (d, 1H), and 7.6 (d, 1H), 7.5 (m, 4H), 6.87 in (d, 2H), 3,74 (t, 4H), 2,98 (m, 4H), 2,3 (s, 3H)
N3-Benzo[1,3]dioxol-5-yl-1-(5-methylpyridin-2-yl)-1H-[1,2,4]triazole-3,5-diamineB1311,203,30DMSO-d6: 8,9 (s, 1H), 8,23 (s, 1H), and 7.8 (d, 1H), EUR 7.57 (m, 3H), 7,33 (s, 1H), 7,05 (d, 1H), 6,8 (d, 1H), to 5.93 (s, 2H), 2,3 (s, 3H)
N3-(7-Methoxybenzo[1,3]dioxol-5-yl)-1-(5-methylpyridin-2-yl)-1H-[1,2,4]triazole-3,5-diamineB1341,203,38DMSO-d6: 8,91(with,1H), 8,23 (s, 1H), and 7.8 (d, 1H), EUR 7.57 (m, 3H), of 6.96 (s, 2H)and 5.9 (s, 2H), of 3.84 (s, 3H), 2,3 (s, 3H)
N3-(4-(Morpholine-4-ylphenyl)-1-(5-triptorelin-2-yl)-1H-[1,2,4]triazole-3,5-diamineB1406,302,85DMSO-d6: 8,93 (s, 1H), up 8.75 (s, 1H), 8,31 (d, 1H), and 7.8 (m, 3H), 7,51 (d, 2H), 6,9 (d, 2H), and 3.72 (m, 4H), 3.0 a (m, 4H)
N3-Benzo[1,3]dioxol-5-yl-1-(5-triptorelin-2-yl)-1H-[1,2,4]triazole-3,5-diamineB1365,203,86DMSO-d6: 9,07 (s, 1H), 8,78 (s, 1H), with 8.33 (d, 1H), and 7.8 (m, 3H), 7,34 (s, 1H), 7,05 (d, 1H), PC 6.82 (d, 1H), to 5.93 (s, 2H)
N3-Benzo[1,3]dioxol-5-yl-1-(6-methylpyridin-2-yl)-1H-[1,2,4]triazole-3,5-diamineB1311,203,35DMSO-d6: 8,9 (s, 1H), a 7.85 (t, 1H), 7,65 (s, 2H), 7,47 (d, 1H), 7,35 (s, 1H), 7,05 (d, 2H), 6,8 (d, 1H), 5,9 (s, 2H), and 2.5 (s, 3H)
N3-(7-Methoxybenzo[1,3]dioxol-5-yl)-1-(6-methylpyridin-2-yl)-1H-[1,2,4]triazole-3,5-diamineB1341,203,40DMSO-d6: 8,91 (s, 1H), 7,86 (t, 1H), 7,65 (s, 2H), 7,45 (d, 1H), 7,05 (d, 1H), 6,95 (d, 2H)and 5.9 (s, 2H), 3,82 (s, 3H), of 2.5 (s, 3H)
N3-(7-Methoxybenzo[1,3]dioxol-5-yl)-1-(5-triptoreline the one-2-yl)-1H-[1,2,4]triazole-3,5-diamine In3395,143,84DMSO-d6: the remaining 9.08 (s, 1H), 8,77 (s, 1H), 8.34 per (d, 1H), 7,80 (t, 3H), of 6.99 (s, 2H), 5,90 (s, 2H), 3,85 (s, 3H)
[4-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)phenyl]morpholine-4-ylmethanolN3366,203,30Methanol-d4: to 8.45 (t, 1H), 7,97 (t, 1H), 7,82 (d, 1H), to 7.67 (d, 2H), 7,45 (d, 2H), 7,25 (m, 1H), 3,85-3,6 (m, 8H)
4-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-N-methyl-N-(1-methylpiperidin-4-yl)benzamidN3407,301,40Methanol-d4: 8,42 (d, 1H), 7,95 (t, 1H), 7,82 (d, 1H), 7,68 (d, 2H), 7,43 (d, 2H), 7,24 (t, 1H), 4,4 (m, 1H), 3,60 (t, 2H), 3.15 in (t, 2H), 2,96 (s, 3H), 2,87 (s, 3H), 2,17 (t, 2H), 2.05 is (m, 2H)
[4-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)phenyl]-(3-aminopyrrolidine-1-yl)methanonN3365,201,00Methanol-d4: 8,42 (t, 1H), 7,95 (t, 1H), 7,80 (d, 1H), 7,69 (d, 2H), 7,55 (d, 2H), 7,22 (m, 1H), 3,99 (t, 2H), 3,88-3,62 (t, 3H), 2,43 (t, 1H), 2,1 (m, 1H)
[4-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)phenyl]-(4-methyl[1,4]diazepan-1-yl)methanonN3393,301,00Methanol-d4: 8,42 (d, 1H), 7,95 (t, 1H), 7,80 (d, 1H), 7,69 (d, 2H), 7,47 (d, 2H), 7,25 (m, 1H), 4,35-to 3.35 (m, 8H), 2.95 and (s, 3H), 2,2 (m, 2H)
[4-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)phenyl]-(4-pyrrolidin-1 and the piperidine-1-yl)methanon N3433,301,50Methanol-d4: 8,42 (d, 1H), 7,95 (t, 1H), 7,80 (d, 1H), 7,69 (d, 2H), 7,42 (d, 2H), 7,22 (m, 1H), 4,4 (t, 2H), to 3.67 (t, 2H), 3.45 points (t, 1H), 3.25 to 3,0 (t, 4H), 2,28-of 1.97 (t, 6N), of 1.66 (m, 2H)
{6-[5-amino-3-(4-(morpholine-4-yl-phenylamino)[1,2,4]triazole-1-yl]pyridine-3-yl}morpholine-4-ylmethanolD3451,201,80Methanol-d4: 8,5 (s, 1H), 8,01 (d, 1H), to 7.84 (d, 1H), 7,73 (d, 2H), 7,45 (d, 2H), was 4.02 (t, 4H), 3-87-3,47 (m, 12H)
{6-[5-amino-3-(4-(morpholine-4-yl-phenylamino)[1,2,4]triazole-1-yl]pyridine-3-yl}-(4-methylpiperidin-1-yl)methanonD3463,901,80Methanol-d4: 8,56 (s, 1H), 8,07 (d, 1H), 7,88 (d, 1H), 7,71 (d, 2H), 7,38 (d, 2H), 4,0 (t, 4H), 3,47 (m, 4H), 3.46 in-3,2 (m, 8H), 2,96 (s, 3H)
6-[5-amino-3-(4-(morpholine-4-yl-phenylamino)[1,2,4]triazole-1-yl]-N-(2-methylaminomethyl)-nicotinamideD3452,302,00Methanol-d4: 8,9 (s, 1H), of 8.37 (d, 1H), a 7.85 (d, 1H), 7,72 (d, 2H), 7,38 (d, 2H), 4,01 (t, 4H), and 3.8 (t, 2H), 3,5 (m, 4H), to 3.41 (t, 2H), 3,01 (s, 6H)
N3-(2,5-Acid)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1313,10, 313,103,40, 3,40DMSO-d6: to 8.45 (d, 1H), with 8.05 (t, 1H), 7,95 (s, 2H), 7,86 (d, 1H), to 7.67 (d, 1H), 7,55 (s, 1H), 7,27 (t, 1H), 6,91(d, 1H), 6,45 (d, 1H), 3,84 (s, 3H), of 3.75 (s, 3H),

DMSO(d6): 8,43 (DD, 1H), 8,02 (TD, 1H), 7,93 (Shir. s, 2H), 7,86 (d, 1H), 7,65 (d, 1), 7,54
N3-Benzo[1,3]dioxol-5-yl-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3297,10, 297,202,82,3,06DMSO-d6: 9,02 (s, 1H), 8,40 (d, 1H), 7,99 (t, 1H), 7,80-the 7.65 (m, 3H), 7,32 (d, 1H), 7,21 (t, 1H), 7,05 (d, 1H), 6,83 (d, 1H), 5,95 (s, 2H)

DMSO: 8,9 (s, 1H), 8,46 compared to 8.26 (d,d, 1H), 8,06-7,88 (m, 1H), 7,72-7,52 (m, 3H), 7,41-7,24 (d, 1H), 7.24 to 7,10 (d,d
1-Pyridin-2-yl-N3-(3,4,5-trimethoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd1343,20, 343,102,90, 2,90(DMSO-d6): 9,0 (s, 1H), 8,42 (d, 1H), 7,98 (t, 1H), of 7.70 (s, 2H), 7,66 (d, 1H), 7,21 (t, 1H), 7,05 (s, 2H), 3,79 (s, 6H), of 3.60 (s, 3H),

(DMSO-d6): 9,0 (s, 1H), 8,42 (d, 1H), 7,98 (t, 1H), of 7.70 (s, 2H), 7,66 (d, 1H), 7,21 (t, 1H), 7,05 (s, 2H), 3,79 (s,
N3-(4-(Morpholine-4-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd1338,502,00DMSO-d6: 9,85 (s, 1H), 8,40 (d, 1H), 7,95 (t, 1H), 7,65 (t, 3H), 7,51 (m, 2H), 7,20 (m, 1H), 6.90 to (m, 2H), 3.75 to (m, 4H), to 3.00 (m, 4H)
4-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-N-(2-morpholin-4-retil)benzamidAnd3409,301,70, 2Methanol-d4: 8,42 (d, 1H), 7,95 (t, 1H), a 7.85 (d, 2H), 7,81 (d, 1H), 7,69 (d, 2H), 7,24 (t, 1H),of 4.11 (m, 2H), 3,85-the 3.65 (m, 6N), 3,39 (m, 2H), 3,2 (m, 2H)
1-(3-Morpholine-4-ylphenyl)-N3-(3,4,5-trimethoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineD*427,30 2,701H NMR (CD3COCD3, 500 MHz): 3,13-3, 19 (m,4H)and 3.59 (s,3H), 3.72 points-of 3.78 (m, 4H), 3,74 (s, 6H), 6,88-6,93 (m, 1H), 6,97 (s, 2H), 7,00? 7.04 baby mortality (m, 1H), 7,10-7,13 (m, 1H), 7,30-7,35 (m, 1H), 8,86 (s, W, 1H)
tert-Butyl ether 4-[4-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)benzoyl]-piperazine-1-carboxylic acidD465,2
tert-Butyl ether 4-[4-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)phenyl]piperazine-1-carboxylic acidD465,2
Benzyl ether of 4-{4-[5-amino-1-(4-cyanophenyl)-1H-[1,2,4]triazole-3-ylamino]-2,6-dimethoxyphenoxy}-piperidine-1-carboxylic acidD570,2
N3-(4-Piperazine-1-ylphenyl)-1-pyrimidine-4-yl-1H-[1,2,4]triazole-3,5-diamine338,002,501H NMR (CD3OD, 500 MHz): 3,30-to 3.41(m, 8H), 7,02 (d, 2H), 7,54 (d, 2H), of 7.75 (d, 1H), 8,73 (d, 1H), 8,96 (s, 1H)

1-phenyl-N3-(3,4,5-trimethoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineA1342,10, 342,202,62, 2,60DMSO-d6: 8,80 (s, 1H), 7,55 (2H),7,63 (d, 2H), 7,50 (t, 2H), 7,28 (m, 1H), 7,01 (s, 2H), 6,47 (s, 2H), 3,74 (s, 6H)and 3.59 (s, 3H), (500 MHz, DMSO-d6) 8,87 (s, 1H), to 7.61 (DD, 2H), 7,50 (t, 2H), 7,30 (m, 1H), 6,97 (s, 2H), 6,65 (Shir. C
1,N3-Diphenyl-1H-[1,2,4]triazole-3,5-diamineA3252,2DMSO-d6: of 8.92 (s, 1H), 7,58 (m, 4H), 7.5 (t, 2H), and 7.3 (t, 1H), 7,2 (t, 2H), 6,77 (t, 1H), 6,44 (s, 2H)
Methyl ester 3-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)benzoic acidAnd1311,2DMSO-d6: 9,43 (s, 1H), 8,43 (d, 1H), 8.30 to (m, 1H), 8,02 (t, 1H), to $ 7.91 (d, 1H), of 7.75 (s, 2H), 7,71 (d, 1H), 7,43, (m, 2H), 7,33 (t, 1H), 3,86 (s, 3H)
Methyl ester of 3-[5-amino-1-(3-methoxyphenyl)-1H-[1,2,4]triazole-3-ylamino]benzoic acidAnd3340,2DMSO-d6: was 9.33 (s, 1H), 8,23 (m, 1H), to 7.84 (d, 1H), 7,39 (m, 3H), 7,17 (d, 1H), 7,15 (t, 1H), to 6.88 (d, 1H), of 6.52 (s, 2H), 3,83 (s, 6H)
Methyl ester of 3-[5-amino-1-(4-methoxyphenyl)-1H-[1,2,4]triazole-3-ylamino]benzoic acidAnd3340,2DMSO-d6: was 9.33 (s, 1H), 8,13 (t, 1H), 7,86 (d, 1H), 7.5 (m, 2H), 7,38 (m, 2H), to 7.09 (m, 2H), 6,65 (Sirs,2H), 3,81 (s, 6H)
Methyl ester 3-(5-amino-1-phenyl-1H-[1,2,4]triazole-3-ylamino]benzoic acidAnd3310,2DMSO-d6: 9,3 (s, 1H), 8,15 (m, 1H), a 7.85 (d, 1H), 7,6 (m, 2H) of 7.48 (m, 2H), 7,34 (m, 3H), 6,69 (Sirs, 2H), 3,82 (s, 3H)
N3-(3-Benzyloxyphenyl)-1-(3-methoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineA*3388,3DMSO-d6: 9,0 (s, 1H), and 7.4 (m, 7H), and 7.1 (m, 4H), 6,85 (d, 1H), 6,65 (Sirs, 2H), 6,45 (d, 1H), of 5.05 (s, 2H), and 3.8 (s, 3H)
N3-(3-Benzyloxyphenyl)-1-(4-methoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineA*3388,3DMSO-d6: 9,1 (s, 1H), and 7.3-7.5 (m, 8H), 7,05 (m, 4H), 6,7 (Sirs, 2H), 6,45 (d, 1H), of 5.05 (s, 2H), 3,85 (s, 3H)
N3-(3-Benzyloxyphenyl)-1-phenyl-1H-[1,2,4]triazole-3,5-diamineAnd3358,3DMSO-d6: 9,0 (s, 1H), 7,6 (m, 2H), 7.5 (m, 2H), and 7.4 (m, 2H), 7,35 (m, 5H), and 7.1 (m, 2H), 6,65 (Sirs, 2H), 6,45 (d, 1H), of 5.05 (s, 2H)
1-(3-Methoxyphenyl)-N3-(4-phenoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineA*3374,3DMSO-d6: 9,15 (s, 1H), 7,6 (m, 2H), 7,43 (m, 1H), 7,32 (m, 2H), 7,18 (m, 2H), 7,05 (m, 1H), 7,0 and 6.6 (m, 7H), and 3.8 (s, 3H)
1-(4-Methoxyphenyl)-N3-(4-phenoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineA*3374,3DMSO-d6: 9,1 (s, 1H), and 7.6 (d, 2H), 7.5 (d, 2H), 7,35 (d, 2H), 7,05 (m, 3H), 6,95-of 6.90 (m, 4H), 6,65 (Sirs, 2H), and 3.8 (s, 3H)
N3-(4-Phenoxyphenyl)-1-phenyl-1H-[1,2,4]triazole-3,5-diamineAnd3344,2DMSO-d6: 9,1 (s, 1H), to 7.59 (m, 4H),7,5(m, 2H), 7,31 (m, 3H), 7,05 (m, 1H), 6,95-of 6.90 (m, 4H), 6.75 in (Sirs, 2H)
4-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino]benzoic acidAnd3297,2DMSO-d6: 9,7 (s, 1H), 8,45 (m, 1H), 8,1-in 7.7 (m, 7H), 7,25 (m, 1H)
4-[5-amino-1-(3-methoxyphenyl)-1H-[1,2,4]triazole-3-ylamino]benzoic acidA*3326,2DMSO-d6: at 9.53 (s, 1H), 7,8 (m, 2H), 7,6 (m, 2H), and 7.4 (m, 1H), 7,2, and 7.1 (m, 2H), 6,9 (m, 1H), 6,6 (Sirs 2H), 3,85 (s, 3H)
4-[5-Amino-1-(4-methoxyphenyl)-1H-[1,2,4]triazole-3-ylamino]benzoic acidA*3326,2DMSO-d6: to 9.45 (s, 1H), and 7.8 (d, 2H), and 7.6 (d, 2H), 7.5 (d, 2H), 7,05 (m, 2H), 6.35mm (s, 2H), 3,81 (s, 3H)
4-(5-amino-1-phenyl-1H-[1,2,4]triazole-3-ylamino]benzoic acidAnd3296,2DMSO-d6: 9,5 (s, 1H), 7,8 (m, 2H), 7,65 was 7.45 (m, 6H), 7,33 (m, 1H), 6,55 (s, 2H)
1-(3-Methoxyphenyl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamineA*3282,2DMSO-d6: of 8.95 (s, 1H), 8,18 (s, 1H), 7,55 (d, 2H), 7,39 (t, 1H), 7,25 to 7.1 (m, 3H), 6,85 (d, 1H), 6.75 in (t, 1H), 6,45 (s, 2H), and 3.8 (s, 3H)
1-(4-Methoxyphenyl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamineA*3282,2 DMSO-d6: cent to 8.85 (s, 1H), 7,55 (d, 2H), 7,45 (d, 2H), 7,2 (t, 2H), 7,05 (d, 2H), 6.75 in (t, 1H), and 6.25 (s, 2H), and 3.8 (s, 3H)
N3-(3,4-Acid)-1-(3-methoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineA*3342,2DMSO-d6: 8,7 (s, 1H), 8,15 (s, 1H), 7,35 (m, 2H), 7,15 (m, 2H), 7,05 (d, 1H), 6,85 (m, 2H), 6,45 (s, 2H), 3,82 (s, 3H), of 3.75 (s, 3H), 3,68 (s, 3H)
N3-(3,4-Acid)-1-(4-methoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineA*3342,2DMSO-d6: 8,6 (s, 1H), 8,15 (s, 1H), 7,45 (m, 2H), 7,27 (d, 1H), and 7.1 (d, 1H), 7,05 (d, 2H), 6,8 (d, 1H), and 6.25 (s, 2H), and 3.8 (s, 3H), and 3.7 (s, 3H), 3,68 (s, 3H)
N3-(3,4-Acid)-1-phenyl-1H-[1,2,4]triazole-3,5-diamineAnd3312,2DMSO-d6: 8,7 (s, 1H), to 7.61 (d, 2H), 7.5 (t, 2H), 7,27 (m, 2H), 7,11 (d, 1H), PC 6.82 (d, 1H), 6,41 (s, 2H, in), 3.75 (s, 3H), 3,68 (s, 3H)
N3-(4-Phenoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3345,2DMSO-d6: 9,17 (s, 1H), and 8.4 (d, 1H), 7,99 (t, 1H), and 7.7 (m, 5H), 7,35 (m, 2H), 7,2 (t, 1H), 7,05 (t, 1H), 7,0 (d, 2H), 6,92 (m, 2H)
[4-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)phenyl]methanolAnd3283,2DMSO-d6: the remaining 9.08 (s, 1H), and 8.4 (m, 1H), 7,98 (t, 1H), and 7.7 (m, 3H), to 7.59 (d, 2H), 7,2 (m, 3H), 5,0 (m, 1H), 4,4 (m, 2H)
3-Benzyl-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine And3267,2DMSO-d6: 8,32 (d, 1H), 7,88 (t, 1H), 7,52 (m, 3H), 7,37 (d, 2H), and 7.3 (m, 2H), 7,21 (t, 1H), 7,11 (m, 1H), 6,56 (t, 1H), 4,32 (d, 2H)
N3-Benzyl-1-(4-methoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd3296,2DMSO-d6: 7,4-7,27 (m, 6H), 7,2 (t, 1H), 6,98 (m, 2H), x 6.15 (t, 1H), equal to 6.05 (s, 2H), 4.25 in (d, 2H), 3,76 (s, 3H)
N3-Benzyl-1-phenyl-1H-[1,2,4]triazole-3,5-diamineAnd3266,2DMSO-d6: 7,5-to 7.18 (m, 10H), and 6.25 (m, 3H), 4,35 (d, 2H)
N3-(3,4-Acid)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3313,2DMSO-d6: 8,88 (s, 1H), scored 8.38 (m, 1H), 7,95 (m, 1H), 7,65 (m, 3H), 7,35 (m, 1H), 7,15 (m, 2H), 6,83 (m, 1H), and 3.8 (s, 3H), 3,68 (s, 3H)
N3-(3-Benzyloxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3359,3DMSO-d6: 9,15 (s, 1H), to 8.41 (d, 1H), 7,97 (m, 1H), and 7.7 (s, 2H), to 7.61 (d, 1H), 7,45 (d, 2H), 7,38 (m, 3H), and 7.3 (m, 1H), 7,15 (m, 3H), and 6.5 (d, 1H), 5,1 (s, 2H)
N3-Biphenyl-3-yl-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd3329,2DMSO-d6: a 9.25 (s, 1H), 8,42 (m, 1H), 8.0 a (m, 1H), and 7.9 (s, 1H), 7,72 (m, 4H), of 7.65 (d, 2H), 7,47 (m, 2H), 7,35 (m, 2H), 7,2 (m, 1H), 7,11 (m, 1H)
1-(3-methoxyphenyl)-N3-(tetrahed furan-2-ylmethyl)-1H-[1,2,4]triazole-3,5-diamine A*3290,2DMSO-d6: 7,65 (Sirs, 2H), 7,46 (t, 1H), and 7.1 (m, 2H), 6,98 (d, 1H), 6,68 (Sirs, 1H), 4,0 (m, 1H), 3,83 (s, 3H), of 3.78 (m, 1H), 3,65 (m, 1H), 3.15 in (m, 2H), 1,92 (m, 1H), of 1.85 (m, 2H), 1.55V (m, 1H)
1-(2-Fluoro-4-itfeel)-N3-(3,4,5-trimethoxyphenyl-1H-[1,2,4]triazole-3,5-diamineAnd2of 486.03,2(500 MHz, DMSO-d6), a total of 8.74 (s, 1H), 7,86 (DD, 1H), 7,68 (DD, 1H), 7,34 (t, 1H), 6,91 (s, 2H), 6.42 per (s, 2H), 3,69 (s, 6H), of 3.57 (s, 3H) ppm
4-(5-Amino-3-(benzo[1,3]dioxol-5-ylamino)-[1,2,4]triazole-1-yl]benzoic acidG1340,12,49(500MHz, DMSO-d6) 8,83 (s, 1H), 8,03 (d, 2H), 7,71 (m, 3H), 7,29 (d, 1H), 6,99 (d, 1H), is 6.61 (s, 1H), 5,91 (s, 2H) ppm
1-(6-Chloropyrimidine-4-yl)-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineG*2373,22,751(500 MHz, DMSO-d6) 9,04 (s, 1H), 8,80 (s, 1H), 7,87 (s, 2H), 7,58 (s, 1H), 7,50 (d, 2H), 6,91 (d, 2H), to 3.73 (m, 4H), 3,01 (m, 4H) ppm
1-(6-Chloropyrimidine-4-yl)-N3-(2,4-differenl)-1H-[1,2,4]triazole-3,5-diamineG*1324,1to 3.58(500 MHz, DMSO-d6) 8,84 (s, 1H), 8,81 (s, 1H), 8,13 (m, 1H), to 7.93 (s, 2H), to 7.59 (s, 1H), 7,24 (m, 1H), 7,07 (m, 1H) ppm
1-(6-Chloropyrimidine-4-yl)-N3-(2-methoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineG*1318,1the 3.8 (500 MHz, DMSO-d6) 8,82 (s, 1H), 8,13 (d, 1H), 7,94 (s, 2H), 7,66 (s, 1H), 7,55 (s, 1H), 6,99 (m, 2H), 6,91 (d, 1H), a 3.87 (s, 3H) ppm
1-(6-Chloropyrimidine-4-yl)-N3-indan-4-yl-1H-[1,2,4]triazole-3,5-diamineG*1328,2as 4.02(500 MHz, DMSO-d6) 8,81 (s, 1H), 8.30 to (s, 1H), 7,88 (s, 2H), 7,79 (d, 1H),at 7.55 (d, 1H), 7,12 (t, 1H), 6,83 (d, 1H), 2,88 (m, 4H), for 2.01 (m, 2H) ppm
4-[5-Amino-3-(3,4,5-trimethoxybenzylamine)-[1,2,4]triazole-1-yl]benzoic acidC2386,1
N5-(3, 5dimethylphenyl)-1-thiazol-yl-1H-[1,2,4]triazole-3,5-diamineA2287,10the 3.8DMSO: 9,96, S,1H; of 7.64, d, 1H; 7,43, d, 1H; 7,28, s, 2H; 6,68, s, 1H; between 6.08, Sirs, 2H; 2,22, s, 6H
N3-(3, 5dimethylphenyl)-1-(4-methylthiazole-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd2301,104,2Acetone-d6: 7,32, s, 2H; 6,87, s, 1H; of 6.71, s, 1H; 2,38, s, 3H; and 2.26, s, 6H
1-Benzothiazol-2-yl-N3-(3, 5dimethylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd1337,104,6DMSO-d6: a 9.25 (s, 1H); 8,08 (d, 1H); 7,86 (d, 1H); 7,78 (Sirs, 2H); 7,51 (DD, 1H); 7,34 (DD, 1H); 7,21 (s, 2H); 6,50 (s, 1H); 2,22 (s, 6H)
1-Benzothiazol-2-yl-N3-(3,5-acid)-1H-[1,2,4]triazole-3,5-diamineAnd1369,2 4,1DMSO-d6: 9,41 (s, 1H); of 8.06 (d, 1H); 7,86 (d, 1H); 7,76 (Sirs, 2H); of 7.48 (DD, 1H); 7,39 (DD, 1H); to 6.88 (s, 2H); 6,03 (s, 1H); 3,76 (s, 6H), 1H NMR (DMSO-d6): 3,74 (6H, s), the 6.06 (1H, t), 6.89 in (2H, d), 7,37 (1H, t)to 7.50 (1H, t), 7,81 (2H, s), 7,87 (1H, d), 8,
1-Benzothiazol-2-yl-N3-(3-methoxy-5-triptoreline)-1H-[1,2,4]triazole-3,5-diamineAnd1407,10the 4.7DMSO-d6: 9,82 (s, 1H); 8,10 (d, 1H); to $ 7.91 (Sirs, 2H); 7,86 (d, 1H); 7,58 (s, 1H); 7,52 (s, 1H); to 7.50 (DD, 1H); 7,34 (DD, 1H); 6,74 (s, 1H); 3,86 (s, 3H)
3-(5-amino-1-benzothiazol-2-yl-1H-[1,2,4]triazole-3-ylamino)-5-cryptomaterialAnd1393,104DMSO-d6: 10,00 (Sirs, 1H); RS 9.69 (s, 1H); 8,08 (d, 1H); 7,80-to 7.95 (m, 3H); 7,45-7,53 (m, 2H); to 7.35 (DD, 1H); 7,30 (s, 1H); 6,55 (s, 1H)
3-[3-(5-amino-1-benzothiazol-2-yl-1H-[1,2,4]triazole-3-ylamino)-5-triptoreline]-propan-1-olAnd1451,204,1DMSO-d6: 9,85 (s, 1H); 8,08 (d, 1H); 7,88 (Sirs, 2H); 7,86 (d, 1H); 7,56 (s, 1H); of 7.48-7,52 (m, 2H); 7,39 (DD, 1H); 6.73 x (s, 1H); 4,11 (t, 2H); of 3.57 (t, 2H); 1.91 a (m, 2H)
N3-(3, 5dimethylphenyl)-1-(5-methylthiazole-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd2301,104,14DMSO-d6: 9,03 (s, 1H); 7,42 (Sirs, 2H); from 7.24 (s, 1H); 7.18 in (s, 2H); 6,47 (s, 1H); to 2.41 (s, 3H); 2,24 (s, 6H)
N5-(3, 5dimethylphenyl)-1-(5-methylthiazole-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd301,104,22DMSO-d6: 9,85 (s, 1H); 7,33 (s, 1H); 7,27 (s, 2H); of 6.68 (s, 1H); 5,99 (Sirs, 2H); of 2.36 (s, 3H); and 2.26 (s, 6H)
N3-(3,5-Acid)-1-(5-methylthiazole-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd2333,13,61DMSO-d6: 9,18 (s, 1H); 7,43 (Sirs, 2H); 7,22 (s, 1H); PC 6.82 (s, 2H); 6,01 (s, 1H); and 3.72 (s, 6H); to 2.42 (s, 3H), DMSO-d6: 9,19 (s, 1H); 7,42 (Sirs, 2H); 7,22 (s, 1H); PC 6.82 (s, 2H); of 6.02 (s, 1H); 3,71 (s, 6H); 2,36 (s, 3H)
N5-(3,5-Acid)-1-(5-methylthiazole-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd2333,103,61DMSO-d6: 9,88 (s, 1H); 7,31 (s, 1H); 6,92 (s, 2H); 6,18 (s, 1H); 5,98 (Sirs, 2H); 3,76 (s, 6H); 2,39 (s, 3H)
N3-(3-Methoxy-5-triptoreline)-1-(5-methylthiazole-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd2371,104,3DMSO-d6: to 9.66 (s, 1H); 7,51 (s, 1H); of 7.48 (Sirs, 2H); 7,46 (s, 1H); 7,28 (s, 1H); 6,66 (s, 1H); of 3.78 (s, 3H); is 2.37 (s, 3H)
N5-(3-Methoxy-5-triptoreline)-1-(5-methylthiazole-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd2371,104,37DMSO-d6: of 10.05 (s, 1H); 7,72 (s, 1H); the 7.65 (s, 1H); to 7.32 (s, 1H); 6.89 in (s, 1H); 6,02 (Sirs 2H); 3,86 (s, 3H); of 2.38 (s, 3H)
N3-(3,5-Acid)-1-thiazol-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd2319,103,31DMSO-d6: which 9.22 (s, 1H); to 7.61 (who, 1H); of 7.48 (Sirs, 2H); 7,40 (d, 1H); 6,86 (s, 2H); 6,00 (s, 1H); and 3.72 (s, 6H)
N5-(3,5-Acid)-1-thiazol-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd2319,103,36DMSO-d6; 9,96 (s, 1H);to 7.59 (d, 1H); 7,41 (d, 1H); 6,92 (s, 2H); of 6.20 (s, 1H); 5,97 (Sirs, 2H); of 3.78 (s, 6H)
N3-(3-Methoxy-5-triptoreline)-1-thiazol-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd2357,10DMSO-d6: 9,68 (s, 1H); to 7.59 (d, 1H); 7,56 (Sirs, 2H); 7,53 (s, 1H); of 7.48 (s, 1H); 7,42 (d, 1H); 6,69 (s, 1H); 3,82 (s, 1H)
N5-(3-Methoxy-5-triptoreline)-1-thiazol-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd2357,104,06DMSO-d6: 10,19 (s, 1H); to 7.77 (s, 1H); to 7.68 (d, 1H); 7,66 (s, 1H); 7,42 (d, 1H); 6.89 in (s, 1H); 6,06 (Sirs, 2H); of 3.84 (s, 3H)
N3-(3-Benzyloxyphenyl)-1-thiazol-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd2365,204,11DMSO-d6: 7,60 (Sirs, 1H); 7,52 (d, 1H); of 7.48 (s, 1H); 7,46 (s, 1H); 7,30-7,40 (m, 6H); 7,22 (DD, 1H); was 7.08 (d, 1H); 7,02 (d, 1H); only 6.64 (d, 1H); 5,10 (s, 2H)
N3-(2-Methoxyphenyl)-1-(5-methylthiazole-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd2303,103,85DMSO-d6: 8,02 (d, 1H); 7,52 (s, 1H); of 7.48 (Sirs, 2H); 7,22 (s, 1H); 6,99 (d, 1H); 6.87 in-6,93 (m, 2H); 3,86 (s, 3H); of 2.38 (s, 3H)
N3-(3-Methoxyphenyl)-1-(5-methylthiazole-2-yl)-1H-[1,2,4]Tria is ol-3,5-diamine And2303,23,59DMSO-d6: 9,23 (s, 1H); 7,43 (Sirs, 2H); 7,34 (s, 1H); 7.23 percent (s, 1H); for 7.12 (DD, 1H); 7.03 is (d, 1H); 6,41 (d, 1H); of 3.78 (s, 3H); 2,39 (s, 3H), DMSO-d6: of 9.21 (s, 1H); 7,42 (Sirs, 2H); 7,31 (s, 1H); 7,22 (s, 1H); 7,11 (DD, 1H); 7.03 is (d, 1H); 6.42 per (d, 1H); 3,74 (s, 3
N3-(4-Methoxyphenyl)-1-(5-methylthiazole-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd2303,203,47DMSO-d6: 8,99 (s, 1H); was 7.45 (d, 2H); 7,38 (Sirs, 2H); from 7.24 (s, 1H); 6,86 (d, 2H); 3,68 (s, 3H); of 2.38 (s, 3H)
N3-(3, 5dimethylphenyl)-1-thiazol-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd2287,204,69DMSO-d6: 9,05 (s, 1H); rate of 7.54 (d, 1H); 7,50 (Sirs, 2H); 7,37 (d, 1H); 7.18 in (s, 2H); 6.48 in (s, 1H); 2,22 (s, 6H)
N3-(2,4-Acid)-1-thiazol-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd2319,204,07DMSO-d6: a 7.85 (d, 1H); at 7.55 (d, 1H); 7,49 (Sirs, 2H); of 7.36 (d, 1H); to 7.32 (s, 1H); 6,60 (d, 1H); 6,50 (m, 1H); is 3.82 (s, 3H); and 3.72 (s, 3H);
N3-(3,4-Acid)-1-thiazol-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd2319,203,49DMSO-d6: 9,02 (s, 1H); 7,58 (d, 1H); 7,49 (Sirs, 2H); 7-42 (s, 1H); 7,39 (d, 1H); 7,02 (d, 1H); to 6.88 (d, 1H); of 3.77 (s, 3H); 3,70 (s, 3H)
N3-(2,5-Dimethoxyphenyl)-1-thiazol-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd2319,204,2DMSO-d6: 7,80 (d, 1H); 7,58 (d, 1H); 7,56 (m, 3H); 7,42 (d, 1H); to 6.88 (d, 1H); to 6.43 (d, 1H); of 3.80 (s, 3H); of 3.75 (s, 3H)
N3-(2,3-Dihydrobenzo[1,4]dioxin-5-yl)-1-thiazol-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd2317,10of 3.77DMSO-d6: 9,02 (s, 1H); 7,58 (d, 1H); 7,51 (Sirs, 2H); 7,39 (d, 1H); 7,21(s, 1H); 6,92 (DD, 1H); 6,76 (d, 1H); 4,18-to 4.14 (m, 4H)
N3-(2-Methoxyphenyl)-1-thiazol-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd2289,204,29DMSO-d6: 8,02 (d, 1H); of 7.60 (d, 1H); EUR 7.57 (Sirs, 2H); 7,51 (s, 1H); 7,41 (d, 1H); 7,00 (d, 1H); 6,95-to 6.88 (m, 2H); 3,86 (s, 3H)
N3-(3-Methoxyphenyl)-1-thiazol-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd2289,203,99DMSO-d6: which 9.22 (s, 1H); to 7.59 (d, 1H); 7,50 (Sirs, 2H); 7,40 (d, 1H); 7,37 (s, 1H); 7,13 (DD, 1H); was 7.08 (d, 1H); 6.42 per (d, 1H); and 3.72 (s, 3H)
N3-(4-Methoxyphenyl)-1-thiazol-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd2289,203,81DMSO-d6: 9,02 (s, 1H); 7,52 (d, 1H); 7,49 (m, 4H); to 7.32 (d, 1H); PC 6.82 (d, 2H); 3,70 (s, 3H)
5-(5-Amino-1-thiazol-2-yl-1H-[1,2,4]triazole-3-ylamino)-2-methoxyphenolAnd2305,203,01DMSO-d6: of 8.92 (s, 1H): 7,56 (d, 1H); 7,50 (Sirs, 2H); 7,42 (d,1H); 7,02 (d, 1H); 6,98 (DD, 1H); 6,86 (d, 1H); of 3.69 (s, 3H)
N3-(3,4-Acid)-1-thiazol-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd333,203,18DMSO-d6: 8,98 (Sirs, 1H); 7,37 (Sirs, 3H); 7.23 percent (s, 1H); 7,01 (d, 1H); PC 6.82 (d, 1H); and 3.72 (s, 3H); 3,62 (s, 3H); 2,32 (s, 3H)
N5-(3, 5dimethylphenyl)-1-thiazol-2-yl-1H-[1,2,4]triazole-3,5-diamineAnd2287,10the 3.8DMSO: 9,96, s, 1H; of 7.64, d, 1H: 7,43, d, 1H; 7,28, s, 2H; 6,68, s, 1H; between 6.08, Sirs, 2H; 2,22, s, 6H
N3-(3, 5dimethylphenyl)-1-(4-methylthiazole-2-yl)-1H-[1,2,4]triazole-3,5-diamineAnd2301,104,2Acetone-d6: 7,32, s, 2H; 6,87, s, 1H; of 6.71, s, 1H; 2,38, s, 3H; and 2.26, s, 6H
1-Benzothiazol-2-yl-N3-(3, 5dimethylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd1337,104,6DMSO-d6: a 9.25 (s, 1H); 8,08 (d, 1H); 7,86 (d, 1H); 7,78 (Sirs, 2H); 7,51 (DD, 1H); 7,34 (DD, 1H); 7,21 (s, 2H); 6,50 (s, 1H); 2,22 (s, 6H)
1-Benzothiazol-2-yl-N3-(3,5-acid)-1H-[1,2,4]triazole-3,5-diamineAnd1369,24,1DMSO-d6: 9,41 (s, 1H); of 8.06 (d, 1H); 7,86 (d, 1H); 7,76 (Sirs, 2H); of 7.48 (DD, 1H); 7,39 (DD, 1H); to 6.88 (s, 2H); 6,03 (s, 1H); 3,76 (s, 6H), 1H NMR (DMSO-d6): 3,74 (6H, s), the 6.06 (1H, t), 6.89 in (2H, d), 7,37 (1H, t)to 7.50 (1H, t), 7,81 (2H, s), 7,87 (1H, d),8,

Example 53

Scheme 20

4-[5-Amino-3-(3,4,5-trimethoxybenzylamine)-[1,2,4]triazole-1-yl]benzamide. When 0°1,1'-carbonyldiimidazole (83 mg, 0.5 mmol) DOB is given to the solution of 4-[5-amino-3-(3,4,5-trimethoxybenzylamine)-[1,2,4]triazole-1-yl]benzoic acid (100 mg, 0.25 mmol) in DMF (3 ml). The reaction mixture was stirred at room temperature for 1 hour and add ammonia (7.0 M in Meon, 1 ml). The reaction mixture was stirred at room temperature for 2 days. The mixture is then purified prepreparation HPLC. FIA-MS: m/e=385,1 (M+N), 381,1 (ES), Rt=3,60 min (method A).1H NMR (500 MHz, DMSO(d6)): 8,87 (s, 1H), 8,02 (Sirs, 1H), to 7.99 (d, 2H), to 7.67 (d, 2H), 7,39 (Sirs, 1H), 7,00 (s, 2H), 6,62 (s, 2H), 3,78 (C, 6N), the 3.65 (s, 3H).

Scheme 21

N3-(5-Amino-2-methoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine and N3-(2-methoxy-5-morpholine-4-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine

Hydrogenation of N3-(5-nitro-2-methoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine 10% Pd/C in a mixed solvent of EtOAc/Meon (1:1) gives N3-(5-amino-2-methoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine.

FIA-MS: m/e=298,2 (M+H). Rt=2,40 min (method A).1H NMR (500 MHz, d-6): to 9.93 (Sirs, 2H), 8,45 (DD, 1H), with 8.33 (d, 1H), 8,00 (TD, 1H), 7,88 (d, 1H), 7,82 (Sirs, 2H), to 7.99 (s, 1H), 7,26 (DD, 1H), was 7.08 (d, 1H), 6.87 in (DD, 1H), 3,90 (s, 3H).

A solution of N3-(5-Amino-2-methoxyphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine (160 mg, 0.5 mmol) and bis-(2-bromatologia ester (140 mg, 0.6 mmol) and isopropylaniline (258 mg, 2 mmol) in a mixture of toluene (30 ml) and DMAC (3 ml) is heated at 110°C for 70 hours. The mixture is concentrated. The residue is purified HPLC, while receiving specified in the title compound (26 mg).

t=2,13 min (method A).1H NMR (500 MHz, d-6): 8,43 (DD, 1H), 8,03 (m, 2H), of 7.90 (m, 1H), 7,68 (d, 1H), 7,56 (Sirs, 1H), 7,26 (DD, 1H), 6,94 (d, 1H), only 6.64 (DD, 1H), 3,80 (s, 3H), 3,28 (Sirs, 4H).

Scheme 22

3-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-4-methoxybenzoic acid

A suspension of methyl ester of 3-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-4-methoxybenzoic acid (1.31 g, of 3.85 mmol) in a mixed solvent of THF (40 ml), Meon (5 ml) and water (10 ml) is treated with 2 N. NaOH (8 ml) at 50°C for 1 hour. The reaction mixture is cooled to room temperature, neutralized 6 N. HCl. A precipitate, which is collected by filtration, thus obtaining specified in the title compound (1.20 g) with a yield of 95%. A small amount of advanced clean HPLC.

FIA-MS: m/e=327,1 (M+N), 325,0 (M-N). Rt=3,09 min (method A).1H NMR (500 MHz, d-6): of 12.53 (s, 1H), 8,81 (d, 1H), 8,43 (DD, 1H), 8,01 (TD, 1H), 7,78 (s, 2H), 7,65 (d, 1H), 7,56 (s, 1H), 7,353 (DD, 1H), 7.23 percent (DD, 1H), 7,07 (DD, 1H), 3,92 (s, 3H).

Scheme 23

3-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-4-methoxybenzamide. A suspension of 3-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-4-methoxybenzoic acid (108 mg, 0.8 mmol) in a mixed solvent of THF (50 ml) and DMF (15 ml) is treated with 1,1'- carbonyl diimidazol (194 mg, 1.2 mmol) at room temperature. 1 hour later we use the t ammonia in the Meon (7.0 M, 1 ml). The reaction mixture was stirred at 50°C for 16 h, poured into water. The precipitate is collected by filtration and further purified HPLC, thus obtaining 3-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-4-methoxybenzamide (112 mg).

FIA-MS: m/e=to 326.1 (M+1). Rt=to 2.65 min (method A).1H NMR (500 MHz, d-6): 8,65 (d, 1H), 8,43 (DD, 1H), 8,02 (TD, 1H), 7,98 (m, 1H), 7,83 (m, 1H), 7,73 (d, 1H), of 7.70 (m, 1H), 7,47 (DD, 1H), 7,27 (ff, 1H), 7,14 (m, 1H),? 7.04 baby mortality (d, 1H), 3,90 (s, 1H).

Similarly receive the following connections:

NameMS (M+N)Retention time, minNMR
[3-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-4-methoxyphenyl]morpholine-4-ylmethanol396,13,09 (method A)DMSO-d6: 8,44 (d, 1H), compared to 8.26 (d, 1H), of 8.06 (m, 2H), 8,02 (t, 1H), 7,88 (s, 1H), to 7.67 (d, 1H), 7,30 (TD, 1H), was 7.08 (d, 1H), 7,02 (d, 1H), 3,90 (s, 1H), 3,60 (m, 4H), 3,55 (m, 4H).
3-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-N-(2-dimethylaminoethyl)-4-methoxybenzamide397,22,79

Method And
DMSO-d6: 9,52 (d, 1H), 8,73 (d, 1H), 8,54 (t, 1H), 8,45 (d, 1H), 8,02 (TD, 1H), 7,86 (m, 1H), 7,72 (d, 1H), 7.62mm (s, 1H), 7,45 (DD, 1H), 7,25 (DD, 1H), was 7.08 (d, 1H), 3,93 (s, 1H), 3,60 (kV, 2H), 3,29 (square, 2N), is 2.88 (s, 3H), of 2.86 (s, 3H).

Scheme 24

4-[5-Amino-3-(2-bromo-3,5-dimethoxy-4-methylphenylimino)-[1,2,4]triazole-yl]benzonitrile

To a suspension of 4-(5-Amino-3-(3,5-dimethoxy-4-methylphenylimino)-[1,2,4]triazole-1-yl]benzonitrile (155 mg, 0.44 mmol) in CCl4(10 ml) and benzene (10 ml) is added N-bromosuccinimide (100 g, of 0.56 mmol) and benzoyl peroxide (10 mg). The reaction mixture is refluxed for 16 hours. Concentrate. The residue is purified HPLC, while receiving specified in the title compound (80 mg).

FIA-MS: m/e=429,1 and 431,1 (M+N), 427,1 and 429,1 (M-N). Rt=3,89 min (method A).1H NMR (500 MHz, DMSO(d6)): to 7.95 (d, 2H), 7,82 (s, 1H), 7,80 (d, 2H), 7,37 (s, 1H), 6,88 (Sirs, 2H), 3,80 (s, 3H), of 3.69 (s, 3H), of 2.08 (s, 3H).

Scheme 25

N3-(4-Amino-5-morpholine-4-yl-2-trifloromethyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine and N-[4-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)-2-morpholine-4-yl-5-trifloromethyl]ndimethylacetamide

A solution of 1-cyano-3-(5-morpholine-4-yl-4-nitro-2-trifloromethyl)-2-phenylazomethine (of 3.60 g, 8 mmol), 2-hydrazinopyridazine (2.0 g, and 18.3 mmol) in DMA (50 ml) was stirred at 110°C for 18 hours. The mixture is evaporated under high vacuum and the residue suspended in water (200 ml) and filtered. The solid is suspended in a mixture of EtOH (50 ml) and EtOAc (30 ml), shaken with 10% Pd/C (835 mg) and 6 N. HCl (2 ml) in an atmosphere of H2(50 psi) for 18 hours. The reaction mixture was filtered through celite and the celite washed with DMF. The filtrate and washing liquid are combined and distilled in high vacuo the e and then lyophilized, while receiving specified in the title compound (2.35 g). A small amount of advanced clean HPLC for biological analysis.

FIA-MS: m/e=437,2 (M+H). Rt=3,14 min (method A).1H NMR (500 MHz, DMSO(d6)): to 8.41 (d, 1H), 8,31 (m, 1H), 8.0 a (t, 1H), of 7.96 (m, 1H), 7,75 (Sirs, 2H), to 7.61 (d, 1H), 7,22 (DD, 1H), 6,93 (m, 1H), 5,0 (Sirs, 2H), 3,79 (m, 4H), of 2.86 (m, 4H).

A solution of N3-(4-amino-5-morpholine-4-yl-2-trifloromethyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine (150 mg, 0.34 mmol) in DMF (6 ml) is treated with pyridine (0.1 ml) and acetic anhydride (0,040 ml) at 23°C for 4 hours. The mixture is concentrated and the residue purified HPLC, while receiving specified in the title compound (43 mg).

FIA-MS: m/e=479,2 (M+H). Rt=3,30 min (method A).1H NMR (500 MHz, DMSO(d6)): DMSO(d6): 8,89 (s, 1H), 8,56 (s, 1H), 8,43 (DD, 1H), 8,19 (s, 1H), 8,02 (TD, 1H), 7,88 (s, 1H), to 7.75 (m, 2H), 7,65 (d, 1H), 7.23 percent (DD, 1H), 3,82 (m, 4H), 2,88 (m, 4H), 2,11 (s, 3H).

Example 54

[4-(5-Amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)phenyl]piperazine-1-ylmethanone. A mixture of tert-butyl ester 4-[4-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)benzoyl]piperazine-1-carboxylic acid (22,1 mg) and triperoxonane acid (0.50 Il) was stirred at room temperature for 1 hour. The reaction mixture is concentrated, thus obtaining specified in the header connection (to 13.6 mg) as a white solid.

MS (ES+): m/z=365,1.1H NMR (CD 3SOCD3, 500 MHz): δ 3,09 is 3.23 (m, 4H), 3,63 is 3.76 (m, 4H), 7,20-7,25 (m, 1H), 7,41 (d, 2H), of 7.64-7,74 (m,4H), 7,95-8,02 (m, 1H), 8,39-8,44 (m, 1H), 8,66-8,95 (m, 2H), 9,44-9,48 (m, 1H).

Example 55

N3-(4-Piperazine-1-ylphenyl)-1-pyridin-2-yl-1H-[1,2,4]triazole-3,5-diamine. Specified in the title compound is obtained from tert-butyl ether 4-[4-(5-amino-1-pyridin-2-yl-1H-[1,2,4]triazole-3-ylamino)phenyl]piperazine-1-carboxylic acid according to the procedure described above.

MS (ES+): m/z=337,20.1H NMR (CD3OD, 500 MHz): δ 3,34-to 3.41 (m, 8H), 7,06 (d, 2H), 7,30 (DD, 1H), 7,53 (d, 2H), 7,82 (d, 1H), 7,97-8,02 (m, 1H), 8,45-8,48 (m, 1H).

Example 56

1-(4-Aminomethylphenol)-N3-[3,5-dimethoxy-4-(piperidine-4-yloxy)phenyl]-1H-[1,2,4]triazole-3,5-diamine. Specified in the title compound is obtained from butyl ester 4-{4-[5-amino-1-(4-cyanophenyl)-1H-[1,2,4]triazole-3-ylamino]-2,6-dimethoxyphenoxy}piperidine-1-carboxylic acid according to the procedure described above.

MS (ES+): m/z=440,20.1H NMR (CD3OD, 500 MHz): δ 1,90-of 2.09 (m, 4H), 3,13-is 3.21 (m, 2H), 3,50-3,59 (m, 2H), 3,82 (C, 6N), 4,19 (s, 2H), 4,29 is 4.35 (m, 1H), 6,93 (s, 2H), to 7.61 (d, 2H), of 7.70 (d, 2H).

Scheme 26

Example 57

4-[5-Amino-3-(4-Morfin-4-yl)phenylamino-[1,2,4]triazole-1-yl]-3-perbenzoate. A mixture of 1-(2-fluoro-4-itfeel)-N3-(4-morpholinomethyl)-1H-[1,2,4]triazole-3,5-diamine (0,48 g 0,99 mol) is of copper cyanide (I) (0.09 g, 0,99 mmol) in NMRA (3 ml) and heated at 55°C for 2 h, then poured into water (75 ml) and filtered, washing with water. The filter residue is suspended in chloroform (100 ml) and methanol (5 ml), refluxed for 2 hours, cooled, filtered and evaporated. Cleaning prepreparation HPLC gives specified in the title compound (0.04 g, yield 9%) as a pale reddish-brown freeze-dried.

In a similar way we obtain the following connections:

NameMS (M+N)Retention time, minNMR
4-[5-Amino-3-(3,4,5-trimethoxybenzylamine)-[1,2,4]triazole-1-yl]-3-perbenzoate385,202,80(500 MHz, DMSO-d6) 8,88 (s, 1H), 8,11 (DD, 1H), 7,82 (m, 2H), 6,93 (s, 2H), 6,70 (Shir. s, 2H), 3,70 (s, 6N), of 3.57 (s, 3H) ppm
4-[5-Amino-3-(4-(morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]-3-perbenzoate380,101,80(500 MHz, DMSO-d6) cent to 8.85 (Shir. s, 1H), 8,12 (DD, 1H), to 7.84 (DD, 1H), to 7.77 (t, 1H), 7,44 (d, 2H), of 6.96 (m, 2H), 6,66 (Sirs, 2H), to 3.73 (m, 4H), to 3.09 (m, 4H) ppm

Example 58

4-[5-Amino-3-(4-(morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]-3-perbenzoate

A mixture of 1-(2-fluoro-4-itfeel)-N3-(4-morpholinomethyl)-1H-[1,2,4]triazole-3,5-diamine (0,48 g 0,99 mmol) and cyanide is a single (I) (0.09 g of 0.99 mmol) in NMRA (3 ml) is heated at 55° C, then poured into water (75 ml) and filtered, washing with water. The filter residue is suspended in chloroform (100 ml) and methanol (5 ml), refluxed for 2 hours, cooled, filtered and evaporated. Cleaning prepreparation HPLC gives specified in the title compound (0.04 g, yield 9%) as a pale reddish-brown freeze-dried.

NameMS (M+N)Retention time, minNMR
4-[5-Amino-3-(3,4,5-trimethoxybenzylamine)-[1,2,4]triazole-1-yl]-3-perbenzoate383,202,80(500 MHz, DMSO-d6) 8,88 (s, 1H), 8,11 (DD, 1H), 7,82 (m, 2H), 6,93 (s, 2H), 6,70 (Sirs, 2H), 3,70 (s, 6N), of 3.57 (s, 3H) ppm
4-[5-Amino-3-(4-(morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]-3-perbenzoate380,101,80(500 MHz, DMSO-d6) cent to 8.85 (Sirs, 1H), 8,12 (DD, 1H), to 7.84 (DD, 1H), to 7.77 (t, 1H), 7,44 (d, 2H), of 6.96 (m, 2H), 6,66 (Sirs, 2H), to 3.73 (m, 4H), to 3.09 (m, 4H) ppm

Scheme 27

Example 59

{4-[5-Amino-3-(benzo[1,3]dioxol-5-ylamino)-[1,2,4]triazole-1-yl]phenyl}morpholine-4-ylmethanol. A mixture of 4-[5-amino-3-benzo[1,3]dioxol-5-ylamino)[1,2,4]triazole-1-yl]benzoic acid (0.15 g, 0.44 mmol), research (0.05 ml, 0.55 mmol) and HBTU (0.21 g, 0.55 mmol) in THF (5 ml) var who're asked at room temperature for 4 hours. The reaction mixture is diluted with water, extracted with a mixture of methanol/dichloromethane, dried (sodium sulfate) and evaporated. Purification of 2 consecutive prepreparation HPLC gives specified in the title compound (0.008 g, yield 5%) as light pink freeze-dried.

In a similar way we obtain the following connections:

NameMS (M+N)Retention time, minNMR
{4-[5-Amino-3-(benzo[1,3]dioxol-5-ylamino)-[1,2,4]triazole-1-yl]phenyl}morpholine-4-ylmethanol409,202,38(500 MHz, DMSO-d6) 8,79 (s, 1H), 7,63 (d, 2H), 7,53 (d, 2H), 7,29 (d, 1H), 6,97 (DD, 1H), 6,77 (d, 1H), 6,50 (s, 2H), 5,90 (s, 2H), 3,4-3,6 (SIRM, 8H) ppm
{4-[5-Amino-3-(benzo[1,3]dioxol-5-ylamino)-[1,2,4]triazole-1-yl]phenyl}-(4-methylpiperazin-1-yl)methanon422,201,27(500 MHz, DMSO-d6) 8,79 (s, 1H), 7.62mm (d, 2H), 7,49 (d, 2H), 7,29 (d, 1H), 6,97 (DD, 1H), 6,77 (d, 1H), 6,50 (s, 2H), 5,90 (s, 2H), 3,5 (Shir. m, 4H), 2,3 (Shir. m, 4H), of 2.21 (s, 3H) ppm
4-[5-Amino-3-(benzo[1,3]dioxol-5-ylamino)-[1,2,4]triazole-1-yl]-N-methylbenzamide353,202,22(500 MHz, DMSO-d6) 8,80 (s, 1H), 8,44 (square, 1H), 7,94 (d, 2H), 7,65 (d, 2H), 7,28 (d, 1H), 6,98 (DD, 1H), 6,78 (d, 1H), 6,54 (s, 2H), 5,91 (s, 2H), 2,80 (d, 3H) ppm
4-[5-Amino-3-(benzo[1,3]dioxol-5-ylamino)-[1,2,4]triazole-1-yl]benzamide39,10 2,09(500 MHz, DMSO-d6) 8,80 (s, 1H), ,7,98 (m, 3H), of 7.64 (d, 2H), 7,35 (s, 1H), 7,28 (d, 1H), 6,98 (DD, 1H), 6,78 (d, 1H), 6,54 (s, 2H), 5,91 (s, 2H), ppm
4-[5-Amino-3-(benzo[1,3]dioxol-5-ylamino)-[1,2,4]triazole-1-yl]-N,N-dimethylbenzamide367,202,36(500 MHz, DMSO-d6) 8,79 (s, 1H), 7.62mm (d, 2H), 7,51 (d, 2H), 7,29 (d, 1H), 6,98 (DD, 1H), 6,77 (d, 1H), of 6.49 (s, 2H), 5,90 (s, 2H), 2,98 (s, 6H) ppm

Example 60

N3-(2,4-acid)-1-[4-1H-tetrazol-5-yl)phenyl]-1H-[1,2,4]triazole-3,5-diamine

4-[5-Amino-3-(2,4-dimethoxyaniline)-[1,2,4]triazole-1-yl]benzonitrile (52 mg, 0.15 mmol) and trimethylsilyl (20 mg, 0,165 mol) are suspended in 1 ml of toluene with a catalytic amount of oxide dibutylamine and heated to 110°C for 18 hours. The toluene is evaporated and the residue purified preparative HPLC, while receiving 13 mg of product as TFA salt.

NameCleaning procedureMS (M+N)Retention time (min)NMR
N3-(2,4-acid)-1-[4-(1H-tetrazol-5-yl)phenyl]-1H-[1,2,4]triazole-3,5-diamine3380,202,61Acetone-d: 8.3 (l, 2N)and 8.1 (d, 1H), 7,9 (d, 2H), 7,3 (Sirs, 1H), 6,7 (Sirs, 2H), and 6.6 (m, 1H), 6,5 (DD, 1H), 3,9 (s, 3H), and 3.8 (s, 3H).

Scheme 28

(a) NMP, 220°, microwave equipment, (b) the substitution Method: Amin, THF, DIEA, boiling under reflux, the method of substitution In: Amin, NMP, 220°, microwave equipment.

Example 61

N3-(4-(Morpholine-4-ylphenyl)-1-(6-piperazine-1-Yeremey-4-yl)-1H-[1,2,4]triazole-3,5-diamine. A mixture of 1-(6-chloropyrimidine-4-yl)-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine (0.11 g, 0.30 mmol), piperazine (0.26 g, 3.0 mmol) and diisopropylethylamine (of 0.21 ml) in THF (100 ml) stirred at the boil under reflux for 3 hours, then cooled and evaporated. Cleaning prepreparation HPLC gives specified in the header of the connection (of 0.13 g, yield 64%) as a pale yellow solid.

The following compounds are obtained from the use specified in similar ways (scheme 28).

NameThe method of substitutionMS (M+N)Retention time (min)NMR
N3-(2,4-Differenl)-1-[6-(4-methylpiperazin-1-yl)pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd388,301,63(500 MHz, DMSO-d6) to 8.62 (s, 1H), of 8.47 (d, 1H), 8,13 (m, 1H), 7,82 (s, 2H), 7.23 percent (m, 1H), 7,02 (m, 1H), 6,86 (s, 1H), 4,55 (d, 2H), 3,54 (d, 2H), 3,29 (t, 2H), 3,11(m, 2H), 2,86 (s, 3H) ppm
1-(6-Diethylaminobenzylidene-4-yl)-N3-(2,4-differeni is)-1H-[1,2,4]triazole-3,5-diamine And361,203,91(500 MHz, DMSO-d6) 8,66 (s, 1H), at 8.36 (s, 1H), 8,04 (m, 1H), to 7.77 (s, 2H), 7,21 (m, 1H), 7,01 (m, 1H), 6,56 (s, 1H), 3,54 (m, 4H)and 1.15 (t, 6H) ppm
N3-(2-Methoxyphenyl)-1-[6-(2-pyrrolidin-1 ylethylamine)pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd396,301,81(500 MHz, DMSO-d6) 9,48 (s, 1H), 8,39 (s, 1H), 8,12 (DD, 1H), 7,87 (DM, 1H), to 7.77 (s, 2H), 7,38 (s, 1H), 7,01 (DD, 1H), 6,91 (m, 2H), 6,70 (s, 1H), a 3.87(with,3H), 3,70 (m, 2H), 3,62 (m, 2H), 3,34 (m, 2H), is 3.08 (m, 2H), 2,02 (m, 2H), to 1.87 (m, 2H) ppm
N3-(2,4-Differenl)-1-[6-(2-pyrrolidin-1 ylethylamine)pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd402,301,85(500 MHz, DMSO-d6) to 8.62 (s, 1H), 8,39 (s, 3H), of 8.06 (m, 1H), to 7.84 (s, 1H), of 7.75 (s, 2H), 7,24 (m, 1H), 6,99 (m, 1H), 6,62 (s, 1H), 3,68 (m, 2H), 3,61 (m, 2H), 3,34 (m, 2H), of 3.07 (m, 2H), 2,02 (m, 2H), 1,86 (m, 2H) ppm
N3-Indan-4-yl-1-[6-(2-pyrrolidin-1 ylethylamine)pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd406,302,70(500 MHz, DMSO-d6) 8,39 (s, 1H), 8,08 (s, 3H), a 7.85 (s, 1H), 7,80 (d, 1H), 7,71 (s, 2H), 7,05 (t, 1H), for 6.81 (d, 1H), 6,65 (s, 1H), 3,69 (m, 2H), 3,61 (m, 2H), 3,35 (m, 2H), of 3.07 (m, 2H), 2,86 (m, 4H), 2,01(m, 4H), to 1.86 (m, 2H) ppm
N3-Indan-4-yl-1-[6-(4-methylpiperazin-1-yl)pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd392,302,61(500MHz, DMSO-d6) 8,48 (s, 1H), 8,08 (s, 1H), 7,80 (d, 1H), to 7.77 (s, 2H), was 7.08 (t, 1H), 6,84 (s, 1H), 6,80 (d, 1H), to 4.52 (m, 2), of 3.54 (m, 2H), 3,30 (m, 2H), 3,11 (m, 2H), 2,85 ( m, 7H), 1,99 (m, 4H), ppm
1-[6-(4-Cyclopropylmethyl-1-yl)pyrimidine-4-yl]-N3-indan-4-yl-1H-[1,2,4]triazole-3,5-diamineAnd418,302,15(500 MHz, DMSO-d6) 8,48 (s, 1H), 8,10 (s, 1H), 7,80 (d, 1H), to 7.77 (s, 2H), 7,07 (t, 1H), 6,84 (s, 1H), for 6.81(d, 1H), 4.53-in (lat. m, 2H), 3,59 (Shir. m, 2H), 3,30 (Shir. m, 4H), 2,86 (m, 5H), of 1.99 (m, 2H), 0,97 (Shir. m, 2H), 0,84 (Shir. m, 2H) ppm
1-[6-(4-Cyclopropylmethyl-1-yl)pyrimidine-4-yl]-N3-(2-methoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd408,301,88(500 MHz, DMSO-d6) 8,48 (s, 1H), 8,16 (DD, 1H), to 7.84 (s, 2H), 7,38 (s, 1H), 7,00 (DD, 1H), 6,99 (t, 3H), 4,6 (Shir. m, 2H), a 3.87 (s, 3H), 3,6 (Shir. m, 2H), 3,30 (Shir. m, 4H), 2,9 (Shir. m, 1H), 0,98 (Shir. m, 2H), 0,85 (Shir. m, 2H) ppm
1-[6-(4-Cyclopropylmethyl-1-yl)pyrimidine-4-yl]-N3-(2,4-differenl)-1H-[1,2,4]triazole-3,5-diamineAnd414,302,45(500 MHz, DMSO-d6) 8,64 (s, 1H), of 8.47 (s, 1H), 8,12 (m, 1H), 7,82 (s, 2H), 7.23 percent (m, 1H), 7,01(m, 1H), 6,83 (s, 1H), 4,5 (Shir. m, 2H), 3,6 (Shir. m, 2H), 3,30 (Shir. m, 4H), 2,85 (Shir. m, 1H), 0,95 (Shir. m, 2H), 0,83 (Shir. m, 2H) ppm
N3-(4-(Morpholine-4-ylphenyl)-1-[6-(2-pyrrolidin-1 ylethylamine)pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd451,300,24(500 MHz, DMSO-d6) 8,91(s, 1H), scored 8.38 (s, 1H), to 7.84 (s, 1H), of 7.70 (s, 2H), 7,50 (d, 2H), 6.90 to (d, 2H), 6,66 (s, 1H), 3,76 (m, 4H), of 3.69 (m, 2H), 3,62 (Shir. m, 2H), 3,35 (m, 2H), 3.04 from (m, 6N), 2,02 (m, 2H), to 1.86 (m, 2H) who d
N3-(4-(Morpholine-4-ylphenyl)-1-(6-piperazine-1-Yeremey-4-yl)-1H-[1,2,4]triazole-3,5-diamineAnd423,301,98(500 MHz, DMSO-d6) 8,93 (s, 1H), 8,88 (s, 1H), 8,45 (s, 1H), 7,76 (s, 2H), 7,53 (d, 2H), 6,94 (d, 2H), PC 6.82 (s, 1H), with 3.89 (m, 4H), 3,76 (m, 4H), 3,24 (m, 4H), 3,05 (m, 4H) ppm
1-[6-(4-Methylpiperazin-1-yl)pyrimidine-4-yl]-N5-(4-(morpholine-4-ylphenyl-1H-[1,2,4]triazole-3,5-diamineAnd437,302,30(DMSO-d6, 500 MHz) 10,85 (s, 1H), 8,54 (d, 1H)" 7,58 (DD, 2H), of 6.96 (d, 2H), 6,76 (s, 1H), 5,80 (width, 2H), 4,5 (Shir. m, 2H), 3.75 to (m, 4H), 3,53 (m, 2H), 3,29 (m, 2H), 3,10 (m, 2H), of 3.07 (m, 4H), 2,85 (s, 3H) ppm
1-[6-(4-Cyclopropylmethyl-1-yl)pyrimidine-4-yl]-N3-morpholine-4-yl-phenyl-1H-[1,2,4]triazole-3,5-diamineAnd463,402,07(500MHz, DMSO-d6) of 8.92 (s, 1H), of 8.47 (s, 1H), 7,76 (s, 2H), 7,53 (d, 2H), 6,92 (d, 2H), 6,86 (s, 1H), 4,5 (SIRM 2N in), 3.75 (m, 4H), 3,6 (Shir. m, 2H), 3,3 (Shir t, 4H), 3.04 from (m, 4H), 2,9 (width m, 1H), and 0.98 (m, 2H), 0,86 (m, 2H) ppm
1-[6-(1-Benzylpyrrolidine-3-ylamino)pyrimidine-4-yl]-N3-phenyl-1H-[1,2,4]triazole-3,5-diamineIn4281H NMR (500 MHz, CDC13) 8,32 (1H, s)to 7.50 (2H, d), 7,3 1(7H, m), to 6.95 (1H, t), of 6.65 (1H, s), 6,63 (1H, in), 3.75 (2H, DD), 2,90 (1H, m)of 2.75 (1H, m), 2,70 (1H, m), 2.40 a (2H, m) ppm

2-[6-(5-Amino-3-phenylamino-[1,2,4]triazole-1-yl)pyrimidine-4-ylamino]-2-phenylethanol In3891H NMR (500 MHz, DMSO-d6) d 9,10 (1H, s), of 8.28 (1H, s), 8,10 (1H, Shir), the 7.65 (5H, m), 7,43-7,20 (7H, m), 6,85 (1H, t), to 5.21 (1H, Shir s)of 4.95 (1H, Shir), the 3.65 (2H, Shir. (C) M.D.
1-{6-[1-(4-Methoxyphenyl)-ethylamino]pyrimidine-4-yl}-N3-phenyl-1H-[1,2,4]triazole-3,5-diamineIn403,33,51H NMR (500 MHz, DMSO-d6) d remaining 9.08 (1H, s), compared to 8.26 (1H, s), of 8.04 (1H, d), 7,66 (2H, s), to 7.59 (2H, m), 7,34-7,20 (4H, m), 6.89 in (3H, m), 3,70 (3H, s)of 1.44 (3H, d) ppm
1-[6-(Indan-1-ylamino)pyrimidine-4-yl]-N3-phenyl-1H-[1,2,4]triazole-3,5-diamineB385,23,831H NMR (500 MHz, DMSO-d6) d 9,10 (1H, s), 8,39 (1H, s), 8,01 (1H, d), of 7.70 (2H, s), to 7.61 (2H, d), 7,30-7,10 (8H, m), to 6.80 (1H, m), 6,70 (1H, s), 3,30 (2H, m), 3,10-2,80 (3H, m) ppm
1-{6-[1-(4-Forfinal)ethylamino]-pyrimidine-4-yl}-N3-phenyl-1 H-[1,2,4]triazole-3,5-diamineB391,33,611H NMR (500 MHz, DMSO-d6) d is 9.09 (1H, s), compared to 8.26 (1H, s), 8,11 (1H, d), 7,66 (2H, s), to 7.59 (2H, m), 7,42 (2H, m), 7,25 (2H, m), to 7.15 (2H, t), 6,89 (1H, m), and 5.30 (1H, Sirs), a 1.45 (3H, d) ppm
N3-Phenyl-1-[6-(1-phenylpropylamine)-pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineB387,33,761H NMR (500 MHz, DMSO-d6) d is 9.09 (1H, s), compared to 8.26 (1H, s), with 8.05 (1H, d), a 7.62 (2H, s), to 7.59 (2H, m), 7,45-to 7.18 (8H, m), 6.89 in (1H, m), and 5.30 (1H, Shir. C)of 1.80 (2H, m), and 0.9 (3H, m) ppm
3-[6-(5-Amino-3-phenylamino[1,2,4]-triazole-1-yl)pyrimidine-4-ylamino]-3-phenylpropane-1-olB403,22,871H NMR (500 MHz, DMSO-d6) d is 9.09 (1H, s), compared to 8.26 (1H, s)to 8.12 (1H, d), a 7.62 (2H, s), to 7.59 (2H, m), 7,45-to 7.18 (8H, m), 6.89 in (1H, m), and 5.30 (1H, Shir. C)4,55 (1H, m), 3,50 (2H, m), 1,90 (2H, m) ppm

1-[6-(5-Amino-3-phenylamino[1,2,4]-triazole-1-yl)pyrimidine-4-ylamino]indan-2-olIn401,3with 3.271H NMR (500 MHz, DMSO-d6) d is 9.09 (1H, s), 8,32 (1H, s), of 7.70 (3H, s), 7,60 (3H, m), 7,32-7,10 (6N, m), 6.89 in (1H, m), the ceiling of 5.60 (1H, Shir. C)5,08 (1H, Shir. C)4,50 (1H, Shir. C)3,05 (1H, DD), 2,85 (1H, DD) ppm
1-{6-[1-(4-Forfinal)ethylamino]-pyrimidine-4-yl}-N3-phenyl-1H-[1,2,4]triazole-3,5-diamineIn391,33,611H NMR (500 MHz, DMSO-d6) d is 9.09 (1H, s), compared to 8.26 (1H, s), 8,11 (1H, d), 7,66 (2H, s), to 7.59 (2H, m), 7,42 (2H, m), 7,25 (2H, m), to 7.15 (2H, t), 6,89 (1H, m), and 5.30 (1H, Sirs), a 1.45 (3H, d) ppm
1-[6-(5-Amino-3-phenylamino[1,2,4]-triazole-1-yl)pyrimidine-4-ylamino]indan-2-olIn401,3with 3.271H NMR (500 MHz, DMSO-d6) d is 9.09 (1H, s), 8,32 (1H, s), of 7.70 (3H, s), 7,60 (3H, m), 7,32-7,10 (6N, m), 6.89 in (1H, m), the ceiling of 5.60 (1H, Shir. C)5,08 (1H, Shir. C)4,50 (1H, Shir. C)3,05 (1H, DD), 2,85 (1H, DD) ppm
2-[6-(5-Amino-3-phenylamino[1,2,4]-triazole-1-yl)pyrimidine-4-ylamino]the pan-1,3-diol B343,21,91H NMR (500 MHz, MeOD-d4) d 8,30 (1H, s), 7,56 (2H, d), 7.23 percent (2H, t), 6,89 (1H, t), for 6.81 (1H, s), 3,71 (5H, m) ppm
2-[6-(5-Amino-3-phenylamino[1,2,4]-triazole-1-yl)pyrimidine-4-ylamino]propane-1-olB327,22,391H NMR (500 MHz, MeOD-d4) d 8,30 (1H, s), 7,56 (2H, d), 7.23 percent (2H, t), 6,89 (1H, t), 6,77 (1H, s), 4,10 (1H, m), 3,55 (2H, m)of 1.23 (3H, d) ppm
2-[6-(5-Amino-3-phenylamino[1,2,4]-triazole-1-yl)pyrimidine-4-ylamino]-4-methylpentan-1-olB369,33,261H NMR (500 MHz, MeOD-d4) d 8,29 (1H, s), 7,53 (2H, d), 7.23 percent (2H, t), 6,89 (1H, t), 6,74 (1H, s), 3,55 (2H, m), 1,71 (1H, m), 1,50 (2H, t), 0,95 (7H, m) ppm

{1-[6-(5-Amino-3-phenylamino[1,2,4]-triazole-1-yl)pyrimidine-4-ylamino]cyclopentyl}-methanolIn367,33,131H NMR (500 MHz, MeOD-d4) d to 8.70 (1H, s), EUR 7.57 (2H, d), 7,34 (2H, t), 7,30 (1H, t), 7,05 (1H, s), 3,81 (2H, s)2,03 (4H, m), of 1.85 (4H, m) ppm
2-[6-(5-Amino-3-phenylamino[1,2,4]-triazole-1-yl)pyrimidine-4-ylamino]-3-phenylpropane-1-olIn403,283,311H NMR (500 MHz, MeOD-d4) d to 8.20 (1H, s), EUR 7.57 (2H, d), 7,30-7,20 (6N, m), to 7.15 (1H, t), 6,89 (1H, t), 6,69 (1H, s), 3,61 (2H, m), 3,40 (1H, t)of 3.00 (1H, DD), 2,85 (1H, DD) 2,31 (1 is, t), and 2.0 (1H, m) ppm
2-[6-(5-Amino-3-phenylamino[1,2,4]-triazole-1-yl)pyrimidine-4-ylamino]-3-phenylpropane-1-olIn403,283,311H NMR (500 MHz, MeOD-d4) d to 8.20 (1H, s), EUR 7.57 (2H, d), 7,30-7,20 (6N, m), to 7.15 (1H, t), 6,89 (1H, t), 6,69 (1H, s), 3,61 (2H, m), 3,40 (1H, t)of 3.00 (1H, DD), 2,85 (1H, DD), 2,31 (1H, t), and 2.0 (1H, m) ppm
2-[6-(5-Amino-3-phenylamino[1,2,4]-triazole-1-yl)pyrimidine-4-ylamino]-3-methylbutane-1-olIn355,32,871H NMR (500 MHz, CDCl3d 8,11 (1H, s), 7,40 (2H, d), 7,38 (1H, m), 7,21 (3H, m), 7,0 (2H, Shir. C)for 6.81 (1H, t), 6,55 (1H, s), 3,76 (1H, DD), the 3.65 (1H, DD), 0,90 (7H, m) ppm
2-[6-(5-Amino-3-phenylamino[1,2,4]-triazole-1-yl)pyrimidine-4-ylamino]cyclohexanolIn367,33,221H NMR (500 MHz, MeOD-d4) d of 8.27 (1H, s), EUR 7.57 (2H, d), 7,25 (2H, t), 6,89 (1H, t), 6,79 (1H, Shir. C)to 4.01 (1H, m), 1,90-1,40 (N, m) ppm
2-[6-(5-Amino-3-phenylamino[1,2,4]-triazole-1-yl)pyrimidine-4-ylamino]-3-phenylpropionamideIn416,33,421H NMR (500 MHz, MeOD-d4) d 8,24 (1H, s), 7,31-7,20 (6N, m), 7,17 (1H, t), 6,89 (1H, t), PC 6.82 (1H, Shir. C)3,30 (1H, DD), 3,23 (1H, DD), 2,99 M.D.

Amide 1-[6-(5-Amino-3-phenylamino[1,2,4]-triazole-1-yl)pyrimidine-4-yl]piperidine-3-carboxylic acidIn380,32,871H NMR (500 MHz, DMSO-d6) d 9,12 (1H, s), 8,39 (1H, s), of 7.75 (2H, s), to 7.59 (2H, d), 7,38 (1H, Shir. C), 7,20 (2H, t), of 6.90 (1H, s), to 6.80 (1H, t), of 6.75 (1H, s), 3,05 (2H, m), 2,31 (1H, m), of 1.95 (1H, m), of 1.78 (1H, m)to 1.67 (1H, m)of 1.41 (1H, m) ppm
Amide 1-[6-(5-Amino-3-phenylamino[1,2,4]-triazole-1-yl)pyrimidine-4-yl]piperidine-4-carboxylic acidIn380,32,651H NMR (500 MHz, DMSO-d6) d 9,10 (1H, s)of 8.37 (1H, s), of 7.75 (2H, s), 7,58 (2H, d), 7,30 (1H, Shir. C)of 7.24 (2H, t), for 6.81 (1H, s), to 6.80 (1H, t), of 6.73 (1H, s), 4,35 (2H, m), 3,05 (2H, m), is 2.41 (1H, m), is 1.81 (2H, m)of 1.55 (2H, m) ppm
3-{4-[6-(5-Amino-3-phenylamino[1,2,4]-triazole-1-yl)pyrimidine-4-yl]piperazine-1-yl}-3-oxopropionateIn405,22,721H NMR (500 MHz, CDCl3d 8,31 (1H, s), 7,40 (2H, d), 7,25 (2H, t), 6,89 (1H, t), 6,77 (1H, s), of 6.65 (2H, Shir. C)of 6.45 (1H, s), 3,82 (2H, m), 3,70 (4H, m), 3,52 (2H, m), 3,40 (2H, s) ppm
(1-{6-[5-Amino-3-(2-fluoro-4-morpholine-4-ilfenomeno)[1,2,4]-triazole-1-yl]pyrimidine-4-yl}piperidine-4-yl)methanolB470,32,531H NMR (500 MHz, CDCl3d of 8.28 (1H, s), 8,00 (1H, t), to 6.80 (2H, Shir. C)of 6.71(1H, s)6,70-6,55 (3H, m), 4,42 (2H, m), a 3.87 (4H, m), 3,50 (2H, m), 3,40 (3H, m)of 3.00 (4H, m), of 2.86 (2H, m), of 1.80 (2H, m) ppm
(1-{6-[5-Amino-3-(2-fluoro-4-morpholine-4-ilfenomeno)[1,2,4]-triazole-1-yl]pyrimidine-4-yl}pyrrolidin-2-yl)methanolB456,32,421H NMR (500 MHz, CDCl3d to 8.20 (1H, s), to 7.99 (1H, t), 6,77 2H, Shir. C)6,62 (2H, m), 6,53 (2H, d), of 3.77 (4H, m), of 3.69 (1H, DL)of 3.60 (1H, t), 3,50 (1H, m)of 3.00 (4H, m), is 2.05 (2H, m)to 1.70 (4H, m) ppm

1-{6-[5-Amino-3-(2-fluoro-4-morpholine-4-ilfenomeno)[1,2,4]-triazole-1-yl]pyrimidine-4-yl}pyrrolidin-3-olIn442,32,131H NMR (500 MHz, CDCl3d to 8.40 (1H, s), to 7.93 (1H, t), of 6.90 (2H, Shir. C)6,63 (1H, s), 4,48 (1H, s), 3,85 (4H, m), the 3.65 (2H, Shir. C)of 3.42 (4H, m), 3,20 (1H, m), 2.40 a (2H, m), of 2.15 (2H, m), and 2.0 (2H, m) ppm
1-{6-[5-Amino-3-(2-fluoro-4-morpholine-4-ilfenomeno)[1,2,4]-triazole-1-yl]pyrimidine-4-yl}pyrrolidin-3-olIn442,32,131H NMR (500 MHz, CDCl3d to 8.40 (1H,), TO 7.93 (1H, t), of 6.90 (2H, Shir. C)6,63 (1H, s), 4,48 (1H, s), 3,85 (4H, t), the 3.65 (2H, Shir. C)of 3.42 (4H, t), 3,20 (1H, t), is 2.40 (2H, t), of 2.15 (2H, t), and 2.0 (2H, t) ppm
(1-{6-[5-Amino-3-(2-fluoro-4-morpholine-4-ilfenomeno)[1,2,4]-triazole-1-yl]pyrimidine-4-ylamino}cyclopentyl)-methanolIn470,3was 2.761H NMR (500 MHz, CDCl3d 8,29 (1H, s), 8,02 (1H, t), 6,82-6,70 (3H, m), 3,82 (4H, m), of 3.77 (2H, s)to 3.09 (4H, m), from 2.00 (2H, m), 1,90 (2H, m), 1,8 (2H, m)to 1.70 (2H, m) ppm
Ethyl ester of 1-{6-[5-amino-3-(2-fluoro-4-morpholine-4-ilfenomeno)[1,2,4]-triazole-1-yl]pyrimidine-4-yl}piperidine-3-carboxylic acid B512,33,571H NMR (500 MHz, CDCl3d of 8.28 (1H, s), of 7.96 (1H, t), to 6.88 (1H, Shir. C)of 6.73 (1H, s)6,70-6,62 (2H, m), of 4.05 (2H, square), of 3.80 (4H, m), or 3.28 (1H, DD) 3,15 (1H, t), to 3.02 (4H, m), 2.49 USD (1H, m), is 2.05 (1H, m)of 1.76 (2H, m), of 1.52 (1H, m)of 1.20 (3H, t) ppm
2-({6-[5-Amino-3-(4-(morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]pyrimidine-4-yl}methylamino)-4-methylpentan-1-olB468,32,651H NMR (500 MHz, CDCl3d 8,21 (1H, s), 7,33 (2H, d), at 6.84 (2H, d), 6,70 (2H, Shir. C)of 6.66 (1H, s)6,40 (1H, s), 3,80 (4H, m), 3,62 (2H, m), to 3.02 (4H, m), 2,89 (3H, s)of 1.50 (2H, m)of 1.42 (1H, m), 1,21 (1H, m), 0,85 (6N, m) ppm

2-({6-[5-Amino-3-(4-(morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]pyrimidine-4-ylamino}-4-methylpentan-1-olInof 454.32,311H NMR (500 MHz, CDCl3d 8,13 (1H, s), 7,33 (2H, d), 7,12 (1H, Shir. C), 6,97 (2H, Shir. C)to 6.80 (2H, d), to 6.57 (1H, s), 3,80 (5H, m), 3,53 (1H, m)of 3.00 (4H, m), 1,60 (1H, m)of 1.34 (2H, m)of 0.90 (3H, m)of 0.85 (4H, m) ppm
(1-{6-[5-Amino-3-(4-(morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]pyrimidine-4-yl}piperidine-3-yl)methanolIn452,32,051H NMR (500 MHz, CDCl3 d 8,24 (1H, s), 7,35 (2H, d), at 6.84 (4H, m), 6,72 (1H, s)to 3.92 (1H, DD), of 3.78 (4H, m), of 3.48 (1H, m)to 3.41 (1H, m), 3,29 (1H, m)of 3.00 (4H, m), of 1.80 (2H, m)to 1.67 (1H, m), 1,50 (1H, m)of 1.36 (1H, m) ppm
(1-{6-[5-Amino-3-(4-(morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]pyrimidine-4-yl}piperidine-3-yl)methanolIn452,32,161H NMR (500 MHz, CDCl3d 8,24 (1H, s), 7,35 (2H, d), at 6.84 (4H, m), 6,72 (1H, s)to 3.92 (1H, DD), of 3.78 (4H, m), of 3.48 (1H, m)to 3.41 (1H, m), 3,29 (1H, m)of 3.00 (4H, t), of 1.80 (2H, t)to 1.67 (1H, m), 1,50 (1H, m)of 1.36 (1H, m) ppm
1-(4-{6-[5-Amino-3-(4-(morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]pyrimidine-4-yl}piperazine-1-yl)alanonIn465,42,021H NMR (500 MHz, MeOD-d4) d scored 8.38 (1H, s), 7,47 (2H, d), to 6.95 (2H, d), PC 6.82 (1H, s), 3,81 (6N, m), 3,78-3,62 (6N, m)is 3.08 (4H, m), 2,12 (3H, s) ppm
Ethyl ester of 4-{6-[5-amino-3-(4-(morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]pyrimidine-4-yl}piperazine-1-carboxylic acidIn495,42,611H NMR (500 MHz, MeOD-d4) d scored 8.38 (1H, s), 7,47 (2H, d), to 6.95 (2H, d), PC 6.82 (1H, s)to 4.15 (2H, square), 3,81 (4H, m), 3,74 (4H, m)and 3.59 (4H, m), is 3.08 (4H, m), 1,25 (3H, t) ppm

(1-{6-[5-Amino-3-(2-methoxy-4-morpholine-4-yl-phenylamino)-[1,2,4]triazole-1-yl]pyrimidine-4-yl}piperidine-3-yl)methanolIn482,42,391H NMR (500 MHz, CDCl3d 8,24 (1H, s), of 7.97 (1H, d), PC 6.82 (1H, s) of 6.75 (1H, C)6,63 (2H, s), 6,50 (1H, DD), 6,46 (1H, s), 3,90 (1H, DD), 3,80 (7H, m), 3,48 (3H, m)to 3.35 (1H, m), and 3.0 (4H, m), equal to 1.82 (2H, m), by 1.68 (1H, m), 1,50 (1H, m)of 1.40 (1H, m) ppm
2-{6-[5-Amino-3-(2-methoxy-4-morpholine-4-yl-phenylamino)-[1,2,4]triazole-1-yl]pyrimidine-4-ylamino}-4-methylpentan-1-olIn484,4to 2.571H NMR (500 MHz, CDCl3d to 8.20 (1H, s), to 7.99 (1H, d), 6.89 in (1H, s)6,70 (2 H, s), 6,60 (1H, s), to 6.43 (2H, m), 3,80 (7H, m), and 3.72 (1H, DD), 3,53 (1H, DD), and 3.0 (4H, m)of 1.64 (1H, m)of 1.40 (2H, m)of 0.93 (3H, d), of 0.87 (3H, d) ppm
2-{6-[5-Amino-3-(2-methoxy-4-morpholine-4-yl-phenylamino)-[1,2,4]triazole-1-yl]pyrimidine-4-yl}-methylamino)-4-methylpentan-1-olIn498,42,91H NMR (500 MHz, CDCl3d 8,29 (1H, s), of 8.04 (1H, d), of 6.90 (1H, s), to 6.80 (2H, s)6,70 (1H, s), to 6.43 (2H, m)to 3.89 (7H, m), 3,70 (2 H, m), 3,10 (4H, m), of 2.92 (3H, s)to 1.61 (2H, m)of 1.30 (1H, m), 0,90 (6N, t) ppm
1-{4-[4-(5-Amino-3-phenylamino-[1,2,4]triazole-1-yl)pyridin-2-yl]piperazine-1-yl}alanonInto 379.21,881H NMR (500 MHz, CDCl3d to 8.20 (1H, d), to 7.93 (1H, s), 7,41 (2H, d), 7,21 (2H, t), 6,89 (1H, t), for 6.81 (1H, s), to 6.80 (1H, d), to 6.39 (1H, s), 3,70 (2 H, m), 3,63 (2H, m), 3,51 (4H, m), 2,10 (3H, s) ppm
[4'-5-Amino-3-phenylamino-{1,2,4]triazole-1-yl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-3-yl]methanolIn366,31,841H NMR (500 MHz, CDCl3d with 8.05 (1H, d), 7,35 (2H, d), 7,20 (2H, t), 7,01 (1H, m), 6,83 (1H, t), of 6.75 (1H, s, of 6.61 (1H, d), of 3.75 (1H, DD), 3,70 (1H, DD), 3,50-3,20 (4H, m)to 1.79 (2H, m), 1,60 (1H, t), of 1.45 (1H, m), 1,25 (1H, m) ppm
1-[6-(4-Chlorpheniramine)-pyrimidine-4-yl]-N3-(2-fluoro-4-morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineIn4824,4
1-[6-(2,5-dimethoxyaniline)-pyrimidine-4-yl]-N3-(2-fluoro-4-methoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineIn453,23,7
N3-(2-Fluoro-4-methoxyphenyl)-1-[6-(5-methoxy-2-methylphenylimino)-pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineIn437,23,7
N3-(2-Fluoro-4-methoxyphenyl)-1-(6-phenylaminopyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineIn393,2the 3.8
2(R)-{6-[5-Amino-3-(2-fluoro-4-methoxybenzylamine)-[1,2,4]triazole-1-yl]pyrimidine-4-ylamino}-4-methylpentan-1-olIn4173,15500 MHz DMSO-d6: 8,8 (Shir. m,1H), 8,459 (Shir. m, 1H), and 8.4 (s, 1H), 7,83 (t, 1H), 6,9 (d, 1H), 6.75 in (m, 2H), 4,2 (m, 1H, in), 3.75 (s, 3H), 3,4 (shirt, 2H), 1,65 (m, 1H), 1,4 (m, 2H), and 0.9 (d, 6H)
2(S)-{6-[5-Amino-3-(2-fluoro-4-methoxybenzylamine)-[1,2,4]triazole-1-yl]pyrimidine-4-ylamino}-4-methylpentan-1-olIn4173,15500 MHz DMSO-d6: 8,8 (Shir. m, 1H), 8,459 (SIRM, 1H), and 8.4 (s, 1H), 7,83 (t, 1H), 6,9 (d, 1H), 6.75 in (m, 2H), 4,2 (m, 1H), 3,5 (, 3H), 3,4 (shirt, 2H), 1,65 (m, 1H), 1,4 (m, 2H), and 0.9 (d, 6H)
(1-{6-[5-Amino-3-(2-fluoro-4-methoxybenzylamine)-[1,2,4]triazole-1-yl]pyrimidine-4-ylamino}cyclopentyl)-methanolIn415of 3.07500 MHz DMSO-d6: 8,7 (Shir. m, 1H), 8,45 (Shir. m, 1H), 7,9 (t, 1H), 6,9 (d, 1H), 6.75 in (m, 2H, in), 3.75 (s, 3H), 3,6 (m, 2H), 1,95 (m, 2H), of 1.75 (m, 2H), 1,65 (m, 2H), and 1.54 (m, H)
(1-{6-[5-Amino-3-(2-fluoro-4-methoxybenzylamine)-[1,2,4]triazole-1-yl]pyrimidine-4-yl}piperidine-4-yl)methanolIn4152,94500 MHz DMSO-d6: 8,65 (Shir. m, 1H), and 8.4 (s, 1H), 7,9 (t, 1H), 6,9 (d, 1H), 6,77 (d, 1H), to 6.67 (s, 1H), 4,4 (m Shir., 1H, in), 3.75 (s, 3H) 3,3 (m, 2H), 3,0 (t, 2H), 2.0 (DM, 1H), 1.77 in (d, 2H), 1,7 (m, 1H), 1,1 (quart., 2H)
2(S)-{6-[5-Amino-3-(2-fluoro-4-morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]pyrimidine-4-ylamino}-2-phenylethanolIn492,22,73500 MHz (DMSO) to 8.25 (s, 1H), 8,19 (m, 1H), 8,07 (m, 1H), 7,83 (DD, 1H), to 7.67 (m, 2H), was 7.36 (m, 2H), 7,31 (DD, 2H), 7.23 percent (DD, 1H), 6,83 (DD, 1H), 6.73 x (m, 1H), 5,22 (m, 1H), 3,74 (m, 4H), to 3.64 (m, 2H), is 3.08 (m, 1H) ppm
Ethyl ester of 4-{6-{5-amino-3-(2-fluoro-4-morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]pyrimidine-4-ylamino}piperidine-1-carboxylic acidIn527,33500 MHz (DMSO) 8,31(s, 1H), 8,18 (m, 1H), 7,78 (DD, 1H), of 7.70 (m, 2H), 7,63 (d, 1H), PC 6.82 (DD, 1H), 6,70 (DD, 1H), is 6.54 (s, 1H), 4,11-was 4.02 (burried m, 1H), 4.04 the (square, 2H), 3,90 (m, 2H), to 3.73 (m, 4H), 3,06 (m, 4H), 2,98 (m, 2H), to 1.87 (m, 2H), 1,32 (m, 2H), 18th (t, 3H) ppm
2(R)-{6-[5-Amino-3-(2-fluoro-4-morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]pyrimidine-4-ylamino}-propan-1-olIn430,22,05500 MHz (DMSO) 8,29 (s, 1H), they were 8.22 (Shir. s, 1H), 7,81 (DD, 1H), 7,72 (m, 2H), 7,54 (m, 1H), 6,83 (DD, 1H), 6,70 (DD, 1H), 6,58 (Shir. s, 1H), 4,10 (m, 1H), to 3.73 (m, 4H), of 3.45 (DD, 1H), 3,34 (m, 1H), 3,06 (m, 4H), of 1.12 (d, 3H) ppm
2(S)-{6-[5-Amino-3-(2-fluoro-4-morpholine-4-ilfenomeno)-[1,2,4]triazole-1-yl]pyrimidine-4-ylamino}-3-methylbutane-1-olIn458,3of 2.51500 MHz (DMSO) of 8.27 (s, 1H), 7,82 (Shir. s, 1H), 7,82 (DD, 1H), 7,71(t, 2H), 7,45 (m, 1H), 6,83 (d, 1H), of 6.71 (d, 1H), 6,67 (Shir. s, 1H), 4.00 points (t, 1H), to 3.73 (m, 4H), 3.46 in (d, 2H), of 3.07 (m, 4H), of 1.92 (m, 1H), from 0.90 (t, 6H) ppm
N3-Phenyl-1-(2-phenylaminopyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamineIn344,22,38500 MHz (DMSO) 10,27 (Shir. s, 1H), 9,24 (s, 1H), of 8.09 (d, 1H), 7,55 (d, 2H), 7,49 (m, 4H), 7,33 (s, 1H), 7,25 (m, 2H), 7.23 percent (t, 2H), 7,09 (Shir. s, 2H), 6,86 (t, 1H) ppm
N3-(2,4-Differenl)-1-[6-(4-methylpiperazin-1-yl)pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd388,301,63(500 MHz, DMSO-d6) to 8.62 (s, 1H), of 8.47 (d, 1H), 8,13 (m, 1H), 7,82 (s, 2H), 7.23 percent (m, 1H), 7,02 (m, 1H), 6,86 (s, 1H), 4,55 (d, 2H), 3,54 (d, 2H), 3,29 (t, 2H), 3,11 (m, 2H), 2,86 (s, 3H) ppm
1-(6-Diethylaminobenzylidene-4-yl)-N3-(2,4-differenl)-1H-[1,2,4]triazole-3,5-diamineAnd361,203,1 (500 MHz, DMSO-d6) 8,66 9s, 1H), at 8.36 (s, 1H), 8,04 (m, 1H), to 7.77 (s, 2H), 7,21 (m, 1H), 7,01 (m, 1H), 6,56 (s, 1H), 3,54 (m, 4H)and 1.15 (t, 6H) ppm
N3-(2-Methoxyphenyl)-1-[6-(2-pyrrolidin-1 ylethylamine)-pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd396,301,81(500 MHz, DMSO-d6) 9,48 (s, 1H), 8,39 (s, 1H), 8,12 (DD, 1H), 7,87 (DM, 1H), to 7.77 (s, 2H), &,38 (s, 1H), 7,01(DD, 1H), 6,91 (m, 2H), 6,70 (s, 1H), a 3.87 (s, 3H), 3,70 (m, 2H), 3,62 (m, 2H), 3,34 (m, 2N), is 3.08 (m, 2H), 2,02 (m, 2H), to 1.87 (m, 2H) ppm
N3-(2,4-Differenl)-1-[6-(2-pyrrolidin-1 ylethylamine)-pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd402,301,85(500 MHz, DMSO-d6) to 8.62 (s, 1H), 8,39 (s, 3H), of 8.06 (m, 1H), to 7.84 (s, 1H), of 7.75 (s, 2H), 7,24 (m, 1H), 6,99 (m, 1H), 6,62 (s, 1H), 3,68 (m, 2H), 3,61 (m, 2H), 3,34 (m, 2H), of 3.07 (m, 2H), 2,02 (m, 2H), 1,86 (m, 2H) ppm
N3-Indan-4-yl-1-[6-(2-pyrrolidin-1 ylethylamine)-pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd406,302,70(500MHz, DMSO-d6) 8,39 (s, 1H), 8,08 (s, 3H), a 7.85 (s, 1H), 7,80 (d, 1H), 7,71 (s, 2H), 7,05 (t, 1H), for 6.81 (d, 1H), 6,65 (s, 1H), 3,69 (m, 2H), 3,61(m, 2H), 3,35 (m, 2H), of 3.07 (m, 2H), 2,86 (m, 4H), 2,01(m, 4H), to 1.86 (m, 2H) ppm
N3-Indan-4-yl-1-[6-(4-methylpiperazin-1-yl)-pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd392,302,61(500 MHz, DMSO-d6) 8,48 (s, 1H), 8,08 (s, 1H), 7,80 (d, 1H), to 7.77 (s, 2H), was 7.08 (t, 1H), 6,84 (s, 1H), 6,80 (d, 1H), to 4.52 (m, 2H), 3,54 (m, 2H), 3,30 (m, 2H), 3,11(m, 2H), 2,85 ( m, 7H), 1,99 (m, 4H), ppm
1-[6-(4-Cyclopropylmethyl-1-yl)pyrimidine-4-yl]-N3-indan-4-yl-1H-[1,2,4]triazole-3,5-diamineAnd418,302,15(500 MHz, DMSO-d6) 848 (s, 1H), 8,10 (s, 1H), 7,80 (d, 1H), to 7.77 (s, 2H), 7,07 (t, 1H), 6,84 (,1H), for 6.81 (d, 1H), 4.53-in (lat. m, 2H), 3,59 (Shir. m, 2H), 3,30 (Shir. m, 4H), 2,86 (m, 5H), of 1.99 (m, 2H), 0,97 (Shir. m, 2H), 0,84 (SIRM, 2H) ppm
1-[6-(4-Cyclopropylmethyl-1-yl)pyrimidine-4-yl]-N3-(2-methoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd408,301,88(500 MHz, DMSO-d6) 8,48 (s, 1H), 8,16 (DD, 1H), to 7.84 (s, 2H), 7,38 (s, 1H), 7,00 (DD, 1H), 6,99 (m, 3H), 4,6 (Shir. m, 2H), a 3.87 (s, 3H), 3,6 (Shir. m, 2H), 3,30 (Shir. m, 4H), 2,9 (Shir. m, 1H), 0,98 (Shir. m, 2H), 0,85 (Shir. m, 2H) ppm
1-[6-(4-Cyclopropylmethyl-1-yl)pyrimidine-4-yl]-N3-(2,4-differenl)-1H-[1,2,4]triazole-3,5-diamineAnd414,302,45(500 MHz, DMSO-d6) 8,64 (s, 1H), of 8.47 (s, 1H), 8,12 (m, 1H), 7,82 (s, 2H), 7.23 percent (m, 1H), 7,01 (m, 1H), 6,83 (s, 1H), 4,5 (Shir. m, 2H), 3,6 (SIRM, 2H), 3,30 (SIRM, 4H), 2,85 (Shir. m, 1H), 0,95 (Shir. m, 2H), 0,83 (Shir. m, 2H) ppm
N3-(4-(Morpholine-4-ylphenyl)-1-[6-(2-pyrrolidin-1 ylethylamine)-pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd451,300,24(500 MHz, DMSO-d6) 8,91(s, 1H), scored 8.38 (s, 1H), to 7.84 (s, 1H), of 7.70 (s, 2H), 7,50 (d, 2H), 6.90 to (d, 2H), 6,66 (s, 1H), 3,76 (m, 4H), of 3.69 (m, 2H), 3,62 (Shir. m, 2H), 3,35 (m, 2H), 3.04 from (m, 6N), 2,02 (m, 2H), to 1.86 (m, 2H) ppm
N3-(4-(Morpholine-4-elfini is)-1-(6-piperazine-1-Yeremey-4-yl]-1H-[1,2,4]triazole-3,5-diamine And423,301,98(500 MHz, DMSO-d6) 8,93 (s, 1H), 8,88 (s, 1H), 8,45 (s, 1H), 7,76 (s, 2H), 7,53 (d, 2H), 6,94 (d, 2H), PC 6.82 (s, 1H), with 3.89 (m, 4H), 3,76 (m, 4H), 3,24 (m, 4H), 3,05 (m, 4H) ppm
1-[6-(4-Methylpiperazin-1-yl)pyrimidine-4-yl]-N5-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd437,302,30(DMSO-d6, 500 MHz) 10,85 (s, 1H), 8,54 (d, 1H), 7,58 (DD, 2H), of 6.96 (d, 2H), 6,76 (s, 1H), 5,80 (width, 2H), 4,5 (Shir. m, 2H, in), 3.75 (m, 4H), 3,53 (m, 2H), 3,29 (m, 2H), 3,10 (m, 2H), of 3.07 (m, 4H), 2,85 (s, 3H) ppm
1-[6-(4-Cyclopropylmethyl-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd463,402,07(500MHz, DMSO-d6) of 8.92 (s, 1H), of 8.47 (s, 1H), 7,76 (s, 2H), 7,53 (d, 2H), 6,92 (d, 2H), 6,86 (s, 1H), 4,5 (Shir. m, 2H, in), 3.75 (m, 4H), 3,6 (Shir. m, 2H), 3,3 (Shir. m, 4H), 3.04 from (m, 4H), 2,9 (Shir. m, 1H), and 0.98 (m, 2H), 0,86 (m, 2H) ppm
1-[6-(2-Diethylaminoethylamine)-pyrimidine-4-yl]-N3-(2-methoxy-4-morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd455,31,8CD3CN: 11,1 (s, 1H), and 8.3(s,1H)and 8.1 (d, 1H), and 6.6 (s, 1H), 6.4 (m, 2H), 5,9 (Sirs, 1H), 4,4 (s, 1H), and 3.8 (s, 3H), and 3.7 (m, 4H), 3,2 (m, 8H), 3.0 a (m, 4H), 2,4 (m, 2H),
1-[6-(2-Diethylaminoethylamine)-pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd425,3DMSO-d6: 8,8 (s, 1H), and 8.3 (s, 1H), 7,65 (Sirs, 2H), 7.5 (d, 2H), 6,85 (d, 2H), 6,65 (Sirs, 1H) 3,7 (m, 4H), 3,4 (Sirs, 2H), 3.0 a (m, 4H), 2,4 (m, 2H), 2,2 (Sirs, 6H),
1-[6-(2-Diethylaminoethylamine)-pyrimidine-4-yl]-N5-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd425,3DMSO-d6: 8,4 (Sirs, 1H), 7,55 (m, 3H), 6,95 (d, 2H), 6,5 (Sirs, 1H), 5,7 (Sirs 2H, in), 3.75 (m, 4H), 3,5 (Sirs, 2H), 3,05 (m, 4H), 2,4 (m, 2H), 2,2 (s, 6H)
1-[6-(3-Methylpiperazin-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd437,330,31DMSO-d6: 8,82 (s, 1H), 8,35 (s, 1H), 7,71 (Sirs,2H), 7,47 (d, 2H), 6.87 in (d, 2H), of 6.68 (s, 1H), 4,25 (m, 1H), 4,15 (m, 1H), and 3.72 (m, 4H), of 2.97 (m, 5H), 2,89 (t, 1H), to 2.67 (m, 2H), 2,53 (m, 1H), 2,34 (m, 1H), was 1.04 (d, 3H)
1-[6-(3-Dimethylaminopropan-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd451,400,80DMSO-d6: 8,82 (s, 1H), 8.34 per (s, 1H), of 7.70 (s, 2H), 7,49 (d, 2H), 6.87 in (d, 2H), to 6.39 (s, 1H), 3,71 (m, 4H), 2,99 (m, 4H), 2.49 USD (C, 7H), 1,86 (Sirs, 1H), 3,9-2,6 (5H),
1-[6-(4-Methyl[1,4]diazepan-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd467,201,46CD3CN: of 8.25 (s, 1H), 7,43 (d, 2H), 6,83 (m, 3H) 6,64 (Sirs, 1H), 3,66 (m, 4H), of 3.57 (m, 2H), is 3.08 (s, 3H), 2,98 (m, 4H), 2,6-2,4 (m, 6H), of 0.95 (t, 6H)
1-{6-[(2-Diethylaminoethyl)-methylamino)pyrimidine-4-yl}-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd467,20 1,46CD3CN: of 8.25 (s, 1H), 7,43 (d, 2H), 6,83 (m, 3H), 6,64 (Sirs,1H), 3,66 (m, 4H), of 3.57 (m, 2H), is 3.08 (s, 3H), 2,98 (ra, 4H), 2,6-2,4 (m, 6H), of 0.95 (t, 6H)
1-[6-(4-Isopropylpiperazine-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd437,201,50DMSO-d6: 9,9 (Sirs, 1H), 8,9 (s, 1H), and 8.4 (s, 1H), 7,75 (Sirs, 2H), 7.5 (d, 2H), 6,9 (d, 2H), 6,8 (s, 1H), 4,5 (m, 2H, in), 3.75 (4H), 3,5 (m, 2H), 3,3 (m, 2H), 3,1 (m, 6H), and 2.8 (s, 3H)
N3-(2,4-Differenl)-1-[6-(4-methylpiperazin-1-yl)pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd388,301,63(500 MHz, DMSO-d6) to 8.62 (s, 1H), of 8.47 (d, 1H), 8,13 (m, 1H), 7,82 (s, 2H), 7.23 percent (m, 1H), 7,02 (m, 1H), 6,86 (s, 1H), 4,55 (d, 2H), 3,54 (d, 2H), 3,29 (t, 2H), 3,11(m, 2H), 2,86 (s, 3H) ppm
1-(6-Diethylaminobenzylidene-4-yl)-N3-(2,4-differenl)-1H-[1,2,4]triazole-3,5-diamineAnd361,203,91(500 MHz, DMSO-d6) 8,66 9s, 1H), at 8.36 (s, 1H), 8,04 (m, 1H), to 7.77 (,2H), 7,21 (m, 1H), 7,01 (m, 1H), 6,56 (s, 1H), 3,54 (m, 4H)and 1.15 (t, 6H) ppm
N3-(2-methoxyphenyl)-1-[6-(2-pyrrolidin-1 ylethylamine)pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd396,301,81(500 MHz, DMSO-d6) 9,48 (s, 1H), 8,39 (s, 1H), 8,12 (DD, 1H), 7,87 (DM, 1H), to 7.77 (s, 2H), &,38 (s, 1H), 7,01 (DD, 1H), 6,91 (m, 2H), 6,70 (s, 1H), a 3.87 (s, 3H), 3,70 (m, 2H), 3,62 (m, 2H), 3,34 (m, 2H), is 3.08 (m, 2H), 2,02 (m, 2H), to 1.87 (m, 2H) ppm
N3-(2,4-Differenl)-1-[6-(2-pyrrolidin-1-iletileri is about)pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamine And402,301,85(500 MHz, DMSO-d6) to 8.62 (s, 1H), 8,39 (s, 3H), of 8.06 (m, 1H), to 7.84 (s, 1H), of 7.75 (s, 2H), 7,24 (m, 1H), 6,99 (m, 1H), 6,62 (s, 1H), 3,68 (m, 2H), 3,61 (m, 2H), 3,34 (m, 2H), of 3.07 (m, 2H), 2,02 (m, 2H), 1,86 (m, 2H) ppm
N3-Indan-4-yl-1-[6-(2-pyrrolidin-1 ylethylamine)pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd406,302,70(500 MHz, DMSO-d6) 8,39 (s, 1H), 8,08 (s, 3H), a 7.85 (s, 1H), 7,80 (d, 1H), 7,71 (s, 2H), 7,05 (t, 1H), for 6.81 (d, 1H), 6,65 (s, 1H), 3,69 (m, 2H), 3,61 (m, 2H), 3,35 (m, 2H), of 3.07 (m, 2H), 2,86 (m, 4H), 2,01 (m, 4H), to 1.86 (m, 2H) ppm
N3-Indan-4-yl-1-[6-(4-methylpiperazin-1-yl)pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd392,302,61(500 MHz, DMSO-d6) 8,48 (s, 1H), 8,08 (s, 1H), 7,80 (d, 1H), to 7.77 (s, 2H), was 7.08 (t, 1H), 6,84 (s, 1H), 6,80 (d, 1H), to 4.52 (m, 2H), 3,54 (m, 2H), 3,30 (m, 2H), 3,11 (m, 2H), 2,85 (m, 7H), 1,99 (m, 4H), ppm
1-[6-(4-Cyclopropylmethyl-1-yl)pyrimidine-4-yl]-N3-indan-4-yl-1H-[1,2,4]triazole-3,5-diamineAnd418,302,15(500 MHz, DMSO-d6) 8,48 (s, 1H), 8,10 (s, 1H), 7,80 (d, 1H), to 7.77 (s, 2H), 7,07 (t, 1H), 6,84 (s, 1H), for 6.81 (d, 1H), 4.53-in (lat. m, 2H), 3,59 (Shir. m, 2H), 3,30 (Shir. m, 4H), 2,86 (m, 5H), of 1.99 (m, 2H), 0,97 (Shir. m, 2H), 0,84 (SIRM, 2H) ppm
1-[6-(4-Cyclopropylmethyl-1-yl)pyrimidine-4-yl]-N3-(2-methoxyphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd408,301,88(500 MHz, DMSO-d6) 8,48 (s, 1H), 8,16 (DD, 1H), to 7.84 (s, 2H), 7,38 (s, 1H), 7,00(DD, 1H), 6,99 (m, 3H), 4,6 (SIRM, 2H), a 3.87 (s, 3H), 3,6 (SIRM, 2H), 3,30 (Shir. m, 4H), 2,9 (SIRM, 1H), 0,98 (SIRM, 2H), 0,85 (SIRM, 2H) ppm
1-[6-(4-Cyclopropylmethyl-1-yl)pyrimidine-4-yl]-N3-(2,4-differenl)-1H-[1,2,4]triazole-3,5-diamineAnd414,302,45(500 MHz, DMSO-d6) 8,64 (s, 1H), of 8.47 (s, 1H), 8,12 (m, 1H), 7,82 (s, 2H), 7.23 percent (m, 1H), 7,01 (m, 1H), 6,83 (s, 1H), 4,5 (Shir. m, 2H), 3,6 (SIRM,2H), 3,30 (SIRM, 4H), 2,85 (SIRM, 1H), 0,95 (SIRM, 2H), 0,83 (SIRM, 2H) ppm
N3-(4-(Morpholine-4-ylphenyl)-1-[6-(2-pyrrolidin-1 ylethylamine)pyrimidine-4-yl]-1H-[1,2,4]triazole-3,5-diamineAnd451,300,24(500 MHz, DMSO-d6) 8,91 (s, 1H), scored 8.38 (s, 1H), to 7.84 (s, 1H), of 7.70 (s, 2H), 7,50 (d, 2H), 6.90 to (d, 2H), 6,66 (s, 1H), 3,76 (m, 4H), of 3.69 (m, 2H), 3,62 (SIRM, 2H), 3,35 (m, 2H), 3.04 from (m, 6N), 2,02 (m, 2H), 1,86 (m, 2H) ppm
N3-(4-(Morpholine-4-ylphenyl)-1-(6-piperazine-1-Yeremey-4-yl)-1H-[1,2,4]triazole-3,5-diamineAnd423,301,98(500 MHz, DMSO-d6) 8,93 (s, 1H), 8,88 (s, 1H), 8,45 (s, 1H), 7,76 (s, 2H), 7,53 (d, 2H), 6,94 (d, 2H), PC 6.82 (s, 1H), with 3.89 (m, 4H), 3,76 (m, 4H), 3,24 (m, 4H), 3,05 (m, 4H) ppm
1-[6-(4-Methylpiperazin-1-yl)pyrimidine-4-yl]-N5-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd437,302,30(DMSO-d6, 500 MHz) 10,85 (s, 1H), 8,54 (d, 1H), 7,58 (DD, 2H), of 6.96 (d, 2H), 6,76 (s, 1H), 5,80 (width, 2H), 4,5 (SIRM 2N in), 3.75 (m, 4H), 3,53 (m, 2H), 3,29 (m, 2H), 3,10 (m, 2H), of 3.07 (m, 4H), 2,85 (s, 3H) ppm
1-[6-(4-Cyclopropylmethyl-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd463,402,07(500 MHz, DMSO-d6) of 8.92 (s, 1H), of 8.47 (s, 1H), 7,76 (s, 2H), 7,53 (d, 2H), 6,92 (d, 2H), 6,86 (s, 1H), 4,5 (Shir. m, 2H), 3.75 to (m, 4H), 3,6 (Shir. m, 2H), 3,3 (Shir. m, 4H), 3.04 from (t, 4H), 2,9 (Shir. m, 1H), and 0.98 (m, 2H), 0,86 (m, 2H) ppm
1-[6-(2-Diethylaminoethylamine)-pyrimidine-4-yl]-N3-(2-methoxy-4-morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd455,31,8CD3CN: 11,1 (s, 1H), and 8.3 (s, 1H)and 8.1 (d, 1H), and 6.6 (s, 1H), 6.4 (m, 2H), 5,9 (Sirs, 1H), 4,4 (s, 1H), and 3.8 (s, 3H), and 3.7 (m, 4H), 3,2 (m, 8H), 3.0 a (m, 4H), 2,4 (m, 2H),
1-[6-(2-Diethylaminoethylamine)-pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd425,3DMSO-d6: 8,8 (s, 1H), and 8.3 (s, 1H), 7,65 (Sirs, 2H), 7.5 (d, 2H), 6,85 (d, 2H), 6,65 (Sirs, 1H), and 3.7 (m, 4H), 3,4 (Sirs, 2H), 3.0 a (m, 4H), 2,4 (m, 2H), 2,2 (Sirs, 6H)
1-[6-(2-Diethylaminoethylamine)-pyrimidine-4-yl]-N5-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd425,3DMSO-d6: 8,4 (Sirs, 1H), 7,55 (m, 3H), 6,95 (d, 2H), 6,5 (Sirs, 1H), 5,7 (Sirs, 2H, in), 3.75 (m, 4H), 3,5 (Sirs, 2H), 3,05 (m, 4H), 2,4 (m, 2H), 2,2 (s, 6H)
1-[6-(3-Methylpiperazin-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd437,330,31 DMSO-d6: 8,82 (s, 1H), 8,35 (s, 1H), 7,71 (Sirs, 2H), 7,47 (d, 2H), 6.87 in (d, 2H), of 6.68 (s, 1H), 4,25 (m, 1H), 4,15 (m, 1H), and 3.72 (m, 4H), of 2.97 (m, 5H), 2,89 (t, 1H), to 2.67 (m, 2H), 2,53 (m, 1H), 2,34 (m, 1H), was 1.04 (d, 3H)
1-[6-(3-Dimethylaminopropan-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd451,400,80DMSO-d6: 8,82 (s, 1H), 8.34 per (s, 1H), of 7.70 (s, 2H), 7,49 (d, 2H), 6.87 in (d, 2H), to 6.39 (s, 1H), 3,71 (m, 4H), 2,99 (m, 4H), 2.49 USD (C, 7H), 1,86 (Sirs, 1H), 3,9-2,6 (5H),
1-[6-(4-Methyl[1,4]diazepan-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd467,201,46CD3CN: of 8.25 (s, 1H), 7,43 (d, 2H), 6,83 (m, 3H), 6,64 (Sirs, 1H), 3,66 (m, 4H), of 3.57 (m, 2H), is 3.08 (s, 3H), 2,98 (m, 4H), 2,6-2,4 (m, 6H), of 0.95 (t, 6H)
1-{6-[(2-Diethylaminoethyl)-methylamino]pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd467,201,46CD3CN: of 8.25 (s, 1H),7,43 (d, 2H), 6,83 (m, 3H), 6,64 (Sirs, 1H), 3,66 (m, 4H), of 3.57 (m, 2H), is 3.08 (s, 3H), 2,98 (m, 4H), 2,6-2,4 (m, 6H), of 0.95 (t, 6H)
1-[6-(4-Isopropylpiperazine-1-yl)pyrimidine-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamineAnd437,201,50DMSO-d6: 9,9 (Sirs, 1H), 8,9 (s, 1H), and 8.4 (s, 1H), 7,75 (Sirs, 2H), 7.5 (d, 2H), 6,9 (d, 2H), 6,8 (s, 1H), 4,5 (m, 2H, in), 3.75 (4H), 3,5 (m, 2H), 3,3 (m, 2H), 3,1 (m, 6H), and 2.8 (s, 3H)
1-(6-Chloropyrimidine-4-yl]-N3-(2-fluoro-4-morpholine-4-ylphenyl)-1H-[1,2,triazole-3,5-diamine 391,23,02500 MHz (DMSO) 8,79 (C, H), 8,44 (s, 1H), 7,87 (s, 2H), 7,82 (t, 1H), 7,50 (s, 1H), PC 6.82 (DD, 1H), 6,77 (DD, 1H), and 3.72 (m, 4H), of 3.07 (m, 4H) ppm
1-(6-Chloropyrimidine-4-yl]-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine288,153,311H NMR (500 MHz, DMSO-d6) of 9.30 (1H, s), 8,81 (1H, s), to $ 7.91 (2H, s), a 7.62 (3H, m), 7,28 (2H, t), 6.87 in (1H, t) ppm
1-(6-Chloropyrimidine-4-yl]-N3-(2-fluoro-4-methoxyphenyl)-1H-[1,2,4]triazole-3,5-diamine1H NMR (500 MHz, DMSO-d6) 88,80 (d, 1H), charged 8.52 (s, 1H), 7,89 (m, 3H), 7,52 (d, 1H), 6,85 (DD, 1H), 6,79 (DD, 1H) ppm

Scheme 29

(2) Amin, DIEA, p-dioxane, 100° (b) hydrazine, THF, boiling under reflux, (C) 4, DMF, 220°With (microwave equipment)

The following compounds are obtained, as shown and described in scheme 29:

2,80
NameMS (M+N)Retention time (min)NMR
N3-(3-Methoxyphenyl)-1-(2-methyl-6-phenylaminopyrimidine-4-yl)-1H-[1,2,4]triazole-for 3,5-diamine3893,40500 MHz, DMSO-d6: of 9.75 (s, 1H), 9,13 (s, 1H), and 7.8 (s, 2H), 7,65 (d, 2H), 7,35 (m, 2H), and 7.3 (s, 1H), 7,15 (m, 2H), 7,05 (t, 1H), 6,79 (s, 1H), 6,45 (m, 1H, in), 3.75 (s, 3H), 2,52 (s, 3H)
N3-(3-Dimethylamino enyl)-1-(2-methyl-6-phenylaminopyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamine 4022,86500 MHz, DMSO-d6: 9,7 (s, 1H), 8,9 (s, 1H), and 7.8 (s, 2H), and 7.6 (d, 2H), 7,35 (m, 2H), 7,03 (m, 4H), 6.75 in (s, 1H), and 6.25 (d, 1H), and 2.8 (s, 6H), to 2.55 (s, 3H)
N3-(2,4-Acid)-1-(2-methyl-6-phenylaminopyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamine4193,52500 MHz, DMSO-d6: 9,7 (s, 1H), 7,95 (d, 1H), and 7.8 (s, 2H), 7,68 (d, 2H), 7,37 (t, 2H), 7.23 percent (s, 1H), 7,03 (t, 1H), 6,8 (s, 1H), 6,65 (s, 1H), 6,45 (d, 1H), 3,85 (s, 3H), of 3.73 (s, 3H), by 2.55 (s, 3H)
N3-[3-Methoxy-4-(2-morpholine-4-ylethoxy)phenyl]-1-(2-methyl-6-phenylaminopyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamine5182,82500 MHz, DMSO-d6: 10,0 (Shir. m, 1H), 9,68 (s, 1H), 9,03 (s, 1H), 7,81 (s, 2H), and 7.6 (d, 2H), 7,38 (m, 3H), and 7.1 (m, 2H), 6,95 (d, 1H), 6.75 in (s, 1H), 4,25 (m, 2H), 4,0 (m, 2H), and 3.8 (m, 2H), and 3.7 (s, 3H), 3,6 (m, 2H), 3,55 (m, 2H)at 3.25 (m, 2H), and 2.5 (s, 3H)
N3-(2-Methoxyphenyl)-1-(2-methyl-6-phenylaminopyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamine3893,57500 MHz, DMSO-d6: 9,7 (s, 1H), 8,15 (d, 1H),7,85 s, 2H), 7.7 (d, 2H), and 7.4 (s, 1H), 7,38 (m, 2H), 7,03 (t, 1H), 7,01 (d, 1H), 6,92 (m, 2H), 6,83 (s, 2H), 3,83 (s, 3H), of 2.5 (s, 3H)
1-(2-Methyl-6-phenylaminopyrimidine-4-yl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine359of 3.46500 MHz, DMSO-d6: 9,73 (s, 1H), 9,17 (s, 1H), and 7.8 (s, 2H), 7.7 (d, 2H), a 7.62 (d, 2H), 7,35 (m, 2H), 7,25 (m, 2H), 7,05 (t, 1H), 6,83 (t, 1H), for 6.81 (s, 2H), 2,3 (s, 3H)
N3-(3-AMINOPHENYL)-1-(2-methyl-6-phenylaminopyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamine374500 MHz, DMSO-d6: of 10.05 (s, 1H), and 9.7 (s, 1H)and 8.1 (s, 1H), and 7.8 (m, 3H), 7.5 (d, 1H), and 7.4 (s, 1H), 7,35 (m, 2H), 7,05 (t, 1H), 6,85 (d, 1H), to 2.55 (s, 3H)
1-(6-Cyclohexylamino-2-methylpyrimidin-4-yl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine365,303,19(DMSO) 9,10 (s, 1H), 7.23 percent (Sirs, 2H), 7,44 (d, 2H), 7.23 percent (d, 1H), 7.23 percent (DD, 2H), 6,83 (DD, 1H), 6,47 (Shir. s, 1H), 3,91 (m, 1H), is 2.37 (s, 3H), of 1.88 (m, 2H), 1,72 (m, 2H), 1,58 (m, 1H), 1,33 (m, 2H), 1,21 (m, 3H) ppm
1-(6-Cyclohexylamino-2-methylpyrimidin-4-yl)-N3-(2-methoxyphenyl)-1H-[1,2,4]triazole-3,5-diamine395,303,42DMSO) to 8.14 (DD, 1H), to 7.77 (Shir. s, 2H), 7,45 (d, 1H), 7,00 (DD, 1H), 6.90 to (m, 2H), 6.48 in (lat. s, 1H), 3,91(m, 1H), a 3.87 (s, 3H), is 2.37 (s, 3H), of 1.88 (m, 2H), 1,72 (m, 2H), 1,58 (m, 1H), 1,32 (m, 2H), 1,18 (m, 3H) ppm
1-[6-(1-Benzylpiperidine-4-ylamino)-2-methylpyrimidin-4-yl]-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine456,302,13(DMSO) 9,11 (s, 1H), 7,73 (s, 2H), 7,60 (d, 2H), 7,49 (d, 1H), 7,323 (complex m, 4H), 7,25 (m, 3H), at 6.84 (DD, 1H), 6.48 in (s, 1H), 3,92 (m, 1H), 3,48 (s, 2H), 2,78 (m, 2H), is 2.37 (s, 3H), 2,07 (DD, 2H), to 1.86 (m, 2H), a 1.45 (m, 2H) ppm
1-[6-(1-Benzylpiperidine-4-ylamino)-2-methylpyrimidin-4-yl]-N3-(2-methoxyphenyl)-1H-[1,2,4]triazole-3,5-diamine486,302,288,13 (DD, 1H), 7,76 (Shir. s, 2H), 7,50 (d, 1H), 7,31 (m, 5H), 7,25 (DD, 1H), 6,99 (d, 1H), 6.90 to (m, 1H), of 6.49 (s, 1H), 3,91 (m, 1H), a 3.87 (s, 3H), of 3.48 (s, 2H), 2,78 (m, 2H), of 2.38 (s, 3H), 2,07 (DD, 2H), of 1.85 (m, 2H), 1,44 (m, 2H) ppm
1-[6-(1-Benzylpiperidine-4-yl) - Rev. Mino)-2-methylpyrimidin-4-yl]-N3-(3-methoxy-4-(3-morpholine-4-ylpropionic)phenyl]-1H-[1,2,4]triazole-3,5-diamine 532,402,20(DMSO) (to 9.66 (s, 1H), 9,48 (m, 1H), 8,98 (s, 1H), 7,80 (s, 2H), to 7.59 (d, 2H), was 7.36 (m, 3H), was 7.08 (DD, 2H), 6,86 (d, 1H), 6.75 in (s, 1H), was 4.02 (d, 2H), of 3.97 (t, 2H), 3,68 (s, 3H), of 3.65 (t, 2H), 3,51 (d, 2H), 3,30 (m, 2H), 3,11 (DD, 2H), 2,09 (m, 2H) ppm
1-[6-(1-Benzylpiperidine-4-ylamino)-2-methylpyrimidin-4-yl]-N3-(3-methoxy-4-(4-(morpholine-4-albucosi)phenyl]-1H-[1,2,4]triazole-3,5-diamine546,402,24(DMSO) to 9.66 (s, 1H), at 9.53 (m, 1H), to 8.94 (s, 1H), 7,79 (s, 2H), to 7.59 (d, 2H), was 7.36 (DD, 2H), 7,33 (d, 1H), was 7.08 (m, 2H), 6,83 (d, 1H), 6.75 in (s, 1H), 3,99 (d, 2H), 3,92 (DD, 2H), 3,68 (s, 3H), of 3.64 (t, 2H), of 3.45 (d, 2H), 3,20 (m, 2H), 3,06 (m,2H), equal to 1.82 (m,
1-[2-Methyl-6-piperidine-4-ylamino)-pyrimidine-4-yl]-N3-phenyl]-1H-[1,2,4]triazole-3,5-diamine366,301,52(DMSO) to 9.20 (s, 1H), total of 8.74 (m, 2H), 8,10-of 7.70 (m, 3H), 7,60 (d, 2H), 7,25 (DD, 2H), 6,85 (DD, 1H), 6,56 (s, 1H), 4,24 (m, 1H), and 3.31(m, 2H), 3.04 from (m, 2H), 2,46 (s, 3H), of 2.05 (m, 2H), by 1.68 (m, 2H) ppm
N3-(3-Isopropoxyphenyl)-1-(2-methyl-6-phenylaminopyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamine417,224.09 to500 MHz(DMSO) 9,73 (s, 1H), remaining 9.08 (s, 1H), 7,80 (s, 2H), 7,63 (d, 2H), 7,35 (DD, 2H), 7,21 (d, 1H), 7,11-7,03 (complex m, 3H), 6,79 (s, 1H), 6,41(DD, 1H), to 4.52 (m, 1H), 2,47 (hidden s, 3H), of 1.25 (d, 6H) ppm
N3-(2-Forfinal)-1-(2-methyl-6-phenylaminopyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamine377,203,91500 MHz (DMSO) 9,78 (s, 1H), to 8.57 (s, 1H), 8,14 (DD, 1H), 7,80 (Shir. s, 2H), 7,65 (d, 2H), 7,35 (DD, 2H), 7,17 (DD, 1H), 7,12 (DD, 1H, 7,05 (DD, 1H), 6,93 (DD, 1H), 6,79 (s, 1H), 2,5 (implicit s, 3H) ppm
1-(2-Methyl-6-phenylaminopyrimidine-4-yl)-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine444,222,72500 MHz (DMSO) 9,65 (s, 1H), 8,81(s, 1H), (7,72 s, 2H), to 7.67 (d, 2H), 7,49 (d, 2H), 7,35 (DD, 2H),? 7.04 baby mortality (DD, 1H), 6,85 (d, 2H), 6,79 (s, 1H), 3,74 (m, 4H), to 3.00 (m, 4H), 2,5 (implicit s, 3H) ppm
N3-(2-Fluoro-4-morpholinyl-4-ylphenyl)-1-(2-methyl-6-phenylaminopyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamine462,103,51500 MHz (MeOD) to 7.59 (m, 1H), 7,56 (d, 2H), 7,38 (DD, 2H), 7,16 (DD, 1H), 6,85 (m, 2H), 6,76 (m, 1H), 3,85 (m, 3H), and 3.16 (m, 4H), of 2.56 (s, 3H) ppm
1-(2-Methyl-6-phenylaminopyrimidine-4-yl)-N3-m-tolyl-1H-[1,2,4]triazole-3,5-diamine373,303,90
1-(2-Methyl-6-phenylaminopyrimidine-4-yl)-N3-p-tolyl-1H-[1,2,4]triazole-3,5-diamine373,303,90

Example 62

(6-Chloro-2-methylpyrimidin-4-yl)phenylamine

2-Methyl-4,6-dichloropyrimidine (400 mg; of 2.64 mmol) is refluxed in 10 ml of p-dioxane with DIEA (575 μl; 426 mg; 3.3 mmol) and aniline (239 μl; 247 mg; to 2.65 mmol) for 48 h in an atmosphere of N2. The solvent is removed under reduced pressure and the residue distributed between ethyl acetate and 0.5 N. HCl. The organic fraction was washed with water, saturated salt solution and dry the t over Na 2SO4and the solvent is removed under reduced pressure. The crude material is triturated with MTBE, filtered with suction to highlight and washed again MTBE and dried in the air, while receiving 375 mg of a white solid, yield of 64.5%.1H NMR (500 MHz, DMSO-d6) d of 8.9 (s, 1H), and 7.7 (s, 1H), 7,55 (m, 2H), 7,27 (t, 2H), 6,95 (t, 1H), 6,0 (s, 1H), of 2.25 (s, 3H) ppm

Example 63

(6 Hydrazino-2-methylpyrimidin-4-yl)phenylamine. (6-Chloro-2-methylpyrimidin-4-yl)phenylamine (2.83 g; 12.9 mmol) is refluxed in THF (35 ml) with anhydrous hydrazine (5 ml; 4.9 g; 153 mmol) in an atmosphere of N2within 26 hours. The reaction mixture is cooled and the solvent is removed under reduced pressure. The residue is distributed between ethyl acetate and water and the organic phase is washed again with water, saturated salt solution and dried (Na2SO4) and the solvent is removed under reduced pressure. The crude material is dissolved in a minimum amount of methylene chloride (hot) and add 100 ml of hot hexanol and the material is stirred, while it is cooled to ambient temperature. Solid allocate by filtration with suction and washed again with hexane and air-dried, thus obtaining 2.5 g of white powder, yield 89%.

1H NMR (500 MHz, DMSO-d6) d of 8.9 (s, 1H), and 7.7 (s, 1H), 7.5 (d, 2H), 7,26 (t, 2H), 6,9 (who, 1H), 6,0 (s, 1H), 4,15 (s, 2H), 2,3 (s, 3H), ppm; MS (M+H) 216.

Example 64

1-(2-Methyl-6-phenylaminopyrimidine-4-yl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine

(6 Hydrazino-2-methylpyrimidin-4-yl)phenylamine (50 mg; 0,232 mmol) is heated in a sealed vessel in 2 ml of 2-propanol and 60 mg of N-cyano-N'-phenyl-O-phenylazomethine within 8 hours. The reaction mixture is cooled and quenched with water and filtered with suction to highlight solids. The crude material is triturated with warm 2-propanolol and collected by filtration with suction, while receiving 15 mg of a white material, the yield of 18%.

1H NMR (500 MHz, DMSO-d6) d 9,73 (s, 1H), 9,17 (s, 1H), and 7.8 (s, 2H), 7.7 (d, 2H), a 7.62 (d,2H), 7,35 (m, 2H), 7,25 (m, 2H), 7,05 (t, 1H), 6,83 (t, 1H), for 6.81 (s, 1H), 2,53 (s, 3H); MS (M+H) 359.

Scheme 30

(a) Amin, DIEA, p-dioxane, 100° (b) hydrazine, THF, boiling under reflux, (C) 4, DMF, 220°With (microwave equipment), and (d) mCPBA THF/p-dioxane, (e) for ZRY= CN, CONH2(i) KCN, DMSO, (ii) K2CO330% of the H2About2, DMSO; ZRY=OR: (iii) NaOR, DMF; ZRY=HE; (iv) NaOH, DMF; ZRY=N(R')2, v) NH(R')2, THF, 80°C.

As described in scheme 29, receive the following connections:

NameMS (M+N)Retention time (min) NMR
N3-(2-Methoxyphenyl-1-(2-methylsulfanyl-6-phenylaminopyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamine4214,17500 MHz DMSO-d6: 9,9(s,1H), 8,12 (d, meta spl, 1H), 7,85 (Shir. s, 2H), 7,65 (d, 2H), 7,63 (s, 1H), 7,35 (m, 2H), 7,05 (t,1H), 7,02 (d, meta spl, 1H), 6,95 (m, 2H), 6.75 in (s, 1H), 3,85 (s, 3H), by 2.55 (s, 3H)
N3-(3-Methoxyphenyl-1-(2-methylsulfanyl-6-phenylaminopyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamine4214,08500 MHz DMSO-d6; 9,9 (s, 1H), and 9.2 (s, 1H), 7,73 (Shir. s, 1H), 7,63 (d, 2H), 7,33 (t, 2H), 7,0 (s, 1H), 7,19 (m, 2H), 7,07 (t, 1H), 6,7 (s, 1H), 6,45 (m, 1H, in), 3.75 (s, 3H), by 2.55 (s, 3H)
1-(2-Methylsulfanyl-6-phenylaminopyrimidine-4-yl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine3914,10500 MHz DMSO-d6: 10,0 (Shir. s, 1H), 9,38 (Shir. m, 1H), 7.7 (d, 2H), 7,63 (d, 2H), was 7.36 (t, 2H), 7,27 (1 DN), was 7.08 (t, 1H), to 6.88 (t, 1H), 6,77 (s, 1H), and 2.6 (s, 3H)
N3-[3-Methoxy-4-(3-morpholine-4-ylpropionic)phenyl]-1-(2-methylsulfonylamino-4-yl)-1H-[1,2,4]triazole-1-yl] - for 3,5-diamine4732,80500 MHz DMSO-d6: 9,05 (s, 1H), and 8.6 (d, 1H), and 7.7 (s, 2H), 7,37 (d, 1H), 7,27 (d, 1H), and 7.1 (DD, 1H), 6,85 (1H), 3,93 (t, 2H), of 3.78 (s, 3H)and 3.59 (m, 4H), to 2.55 (s, 3H), 2,43-2,35 (2m, 6H)and 1.83 (m, 2H)
1-(2-Methylsulfanyl-pyridin-4-yl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine3003,40500 MHz DMSO-d6: 9,2 (s, 1H), and 8.6 (d, 1H), and 7.7 (s, 2H), and 7.6 (d, 2H), 7,35 (d, 1H), 7,25 (m, 2H), 6,9 (t, 1H), 2,53 (s, 3H)
1-(2-Methylsulfanyl-PI is one-4-yl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine 3153,05500 MHz DMSO-d6: 9,1 (s, 1H), 7,6 (m, 4H), 7,2 (1, 1H), 7,15 (Shir. m, 2H), 6,83 (t, 1H), and 6.3 (s, 1H), 2,42 (s, 3H)
1-(6-Amino-2-methylsulfonylamino-4-yl)-N3-[3-methoxy-4-(3-morpholine-4-ylpropionic)phenyl]-1H-[1,2,4]triazole-3,5-diamine488500 MHz (DMSO-d6) of 7.3 (s, 1H), and 7.1 (d, 1H), 6,93 (d, 1H), 6,4 (1H), a 4.03 (t, 4H), 3,83 (s, 3H), of 3.77 (t, 2H), 3,51 (d, 2H), 3,32 (t, 2H), 3.15 in (t, 2H), 2,53 (s, 3H), of 2.15 (m ,2H)
N3-(3-AMINOPHENYL)-1-(2-methylsulfanyl-6-phenylaminopyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamine4063,25500 MHz (DMSO-d6) 10,15 (s, 1H), and 9.7 (s, l), 8,18 (s, 1H), of 7.75 (d, 2H), 7,45 (s, 1H), 7,44 (d, 1H), and 7.3 (t, 3H), 7,03 (t, 1H), 6,85 (d, 1H), 2,55 (s, 5H) 2 exh
6-(5-Amino-3-phenylamino-[1,2,4]triazole-1-yl)-N2-methyl-N4-phenylpyrimidine-2,4-diamine3743,39500 MHz DMSO-d6: 9,6 (Shir. s, 1H), 9,15 (Shir. s, 1H), 7,72 (d, 2H), and 7.6 (d, 2H), 7,35 (m, 2H), 7,25 (m, 2H), 7,03 (t, 1H), 6,85 (t, 1H), and 6.3 (s, 1H), 2,9 (s, 3H)
6-(5-Amino-3-phenylamino-[1,2,4]triazole-1-yl)-N2-ethyl-N4-phenylpyrimidine-2,4-diamine3883,68500 MHzDMSO-d6: 9,7 (Shir. s, 1H), 9,25 (Shir. s, 1H), 7.7 (d, 2H), 7,53 (d, 2H), 7,35 (m, 2H), 7,25 (m, 2H), 7,05 (Shir. t, 1H), 6,85 (t, 1H), and 6.3 (s, 1H), 3,3 (Shir. quart., 2H)and 1.15 (t, 3H)
6-(5-Amino-3-phenylamino-[1,2,4]triazole-1-yl)-N2-ethyl-N2-methyl-N4-phenylpyrimidine-2,4-diamine4024,01500 MHz DMSO-d6: 9,45 (Shir. with 1H), 9,05 (Shir. s, 1H), 7.7 (d, 2H), 7,65 (Shir. m, 2H), to 7.61 (d, 2H), 7,35 (m, 2H), 7,25 (m, 2H), 6,97 (t, 1H), 6,85 (t, 1H), 6,33 (s, 1H), 3,6 (Shir. quart., 2H), 3,1 (Shir. s, 3H)and 1.15 (t, 3H)
6-(5-Amino-3-phenylamino-[1,2,4]triazole-1-yl)-N4-phenyl-N2-propylpyrimidine-2,4-diamine4024,46500 MHz DMSO-d6: 9,5 (Shir. s, 1H), 9,1 (Shir. s, 1H), 7.7 (d, 2H), to 7.61 (d, 1H), 7,35 (m, 2H), 7,25 (m, 2H), 7,0 (Shir. t, 1H), 6,85 (t, 1H), 6,33 (s, 1H), 3,3 (Shir. quart., 2H), and 1.6 (m, 2H), of 0.95 (t, 3H)
6-(5-Amino-3-phenylamino-[1,2,4]triazole-1-yl)-N2-ethyl-N2-methylpyrimidine-2,4-diamine3262,79500 MHz DMSO-d6: 9,23 (Shir. s, 1H), 7,65 (Shir. m, 2H), and 7.6 (d, 2H), 7,25 (m, 2H), 6,86 (t, 1H), 6,2 (s, 1H), 3,6 (quart, 2H), 3,17 (s, 3H)and 1.15 (t, 3H)
6-(5-Amino-3-phenylamino-[1,2,4]triazole-1-yl)-N2-methyl-pyrimidine-2,4-diamine2982,65500 MHz DMSO-d6:: 9,25 (Sirs, 1H), 7,55 (d, 2H), 7,24 (t, 2H), 6.87 in (t, 1H), 6,15 (Sirs, 1H), 2,9 (Shir. m, 3H)
6-(5-Amino-3-phenylamino-[1,2,4]triazole-1-yl)-N2-propyl-pyrimidine-2,4-diamine3262,75500MHz MeOD-d4: at 7.55 (d, 2H), 7,34 (t, 2H), 7,05 (t, 1H), 6,5 (Shir. s, 1H), 3,4 (t, 2H), 3,2 (s, 2H), 1,7 (the Queen., 2H), 1,05 (Shir. t, 3H)
6-(5-Amino-3-phenylamino-[1,2,4]triazole-1-yl)-N2-ethyl-pyrimidine-2,4-diamine3122,70500 MHz DMSO-d: 6:9,25 (s, 1H), 8,8 (Shir. s, 1H), 8.4V (Shir. s, 2H), 7,9 (wide s, 2H), and 7.6 (d, 2H), 7,25 (m, 2H), at 6.84 (t, 1H), 6,2 (s, 1H), 3,38 (m, 2H), 1,2 (t, 3H)
4-(5-Amino-3-phenyl what Mino-[1,2,4]triazole-1-yl)-6-phenylaminopyrimidine-2-ol 3,19500 MHz, DMSO-d6: 10,5 (Shir. s, 1H) to 9.15 (s, 1H), 7,9 (Shir. s, 2H), 7,66 (d, 4H), to 7.4 (t, 2H), 7,2 (t, 2H), 7,18 (Shir. s, 1H), 6,8 (t, 1H), 6.35mm (Shir. s, 1H)
1-(2-Methoxy-6-phenylaminopyrimidine-4-yl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine3753,68500 MHz DMSO-d6: 9,8 (s, 1H) to 9.15 (s, 1H), and 7.7 (m, 7H), 7,37 (t, 2H), 7,25 (m, 2H), 7,02 (t, 1H), 6,83 (t, 1H), only 6.64 (s, 1H), 3,9 (s, 3H)
1-(2-Isopropoxy-6-phenylaminopyrimidine-4-yl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine4034,01500 MHz DMSO-d6: 9,8 (s, lH) to 9.15 (s, lH), and 7.7 (m, 6H), 7,37 (t, 2H), 7,25 (m, 2H), 7,02 (t, lH), 6,83 (t, lH), only 6.64 (s, lH), of 5.15 (m, 1H), of 1.35 (d, 6H)
N3-Methyl-1-(2-methylsulfanyl-6-phenylaminopyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamine3293,30500 MHz DMSO-d6: 9,83 (s, lH), to 7.93 (Shir. m,2H), 7,68 (d, 2H), 7,35 (m, 2H), 7,02 (t, 1H), only 6.64 (s, 1H), 2,77 (s, 3H), 2,52 (s, 3H)
N3-Cyclohexyl-1-(2-methylsulfanyl-6-phenylaminopyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamine3973,86500 MHz DMSO-d6: to 9.93 (s, 1H), 8,2 (SIRM, lH), the 7.65 (d, 2H), 7,35 (m, 2H), 7,05 (t, 1H), 6,4 (s, 1H), 4,35 (m, 1H), to 2.55 (s, 3H), of 1.93 (m, 2H), 1,72 (m, 2H), 1.55V (m, 1H), 1,25 (m, 4H), of 1.16 (m, 2H)
N3-Cyclohexylmethyl-1-(2-methylsulfanyl-6-phenylaminopyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamine4114,04500 MHz DMSO-d6: 9,7 (s, 1H), 7,65 (d, 2H), 7,5 (s, 2H), 7,32 (m, 2H), 7,05 (t, 1H), 6,5 (s, lH), of 6.02 (m, 1H, of 3.3 (s, 3H), 2.95 and (m, 2H), 1,7 (m, 6H), 1,6 (m, 1H), 1,2 (m, 4H), and 0.9 (m, 2H)
6-[5-Amino-3-(2-fluoro-4-morpholine-4-ilfenomeno-[1,2,4]triazole-1-yl)-N4-phenylpyrimidine-2,4-diamine494,204,19500 MHz (DMSO) 9,78 (s, 1H), 8,21 (s, 1H), of 7.75 (DD, 1H), 7.62mm (d, 2H), to 7.59 (s, 2H), 7,34 (DD, 2H), 7,05 (DD, 1H), 7,82 (DD, 1H), 7,69 (DD, 1H), 6,59 (s, 1H), 3,74 (m, 4H), of 3.07 (m, 4H), 2,52 (s, 3H) ppm

Example 65

(6-Chloro-2-methylsulfonylamino-4-yl)phenylamine

A mixture of 2.00 g (10.2 mmol) of 2-thiomethyl-4,6-dichloropyrimidine heated to 100°With 20 ml of p-dioxane together with (1.8 ml; 1.35 g; 10.2 mmol) and DIEA (0,93 ml; 0.96 g; or 10.3 mmol) of aniline in an atmosphere of N2within 24 hour. The reaction mixture is cooled and the solvent is removed under reduced pressure. The residue is distributed between water and ethyl acetate and the organic layer washed with 0.1 N. HCl, water, saturated salt solution and dried (Na2SO4); the solvent is removed under reduced pressure. The material cures when standing with getting to 2.57 g of a white powder, yield 88%. MS m/e (FIA+) 250/252.

(6 Hydrazino-2-methylsulfonylamino-4-yl)phenylamine

6-Chloro-2-methylsulfonylamino-4-yl)phenylamine (2.7 g; 11 mmol) is heated at boiling under reflux in 25 ml of THF anhydrous hydrazine (2.5 ml; 2,44 g; 76 mmol) for 5 hours in an atmosphere of N2. The reaction mixture is Hledat and the solvent is removed under reduced pressure. The mixture is stirred with 100 ml of water, resulting in the formed white solid. The material is collected by filtration with suction, washed again with water and dried in air, while receiving 2,69 g of a white powder, yield 95%.

MS m/e (FIA+) 246;1H NMR (500 MHz, DMSO-d6) d 9,05 (s, 1H), and 7.8 (s, 1H), 7.5 (d, 2H), 7,25 (2N)and 6.9 (t, 1H), to 5.85 (s, 1H), 4.26 deaths (Shir. s, 2H), of 2.45 (s, 3H) ppm

1-(2-Methylsulfanyl-6-phenylaminopyrimidine-4-yl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine

(6 Hydrazino-2-methylsulfonylamino-4-yl)phenylamine (100 mg, 0.40 mmol) is heated with N-cyano-N'-phenyl-O-phenylazomethine (96 mg, 0.44 mmol) in 0.5 ml of DMSO in a sealed tube for 4 hours at 100°C. the Reaction is quenched with water and the resulting solid substance produce by filtration with suction. The solid is washed with water and transferred into a round bottom flask with acetonitrile and the solvent is removed under reduced pressure. HPLC (gradient eluent: water-acetonitrile, with 0.1% TFA) to give 15 mg of a beige powder, yield of 11%.

MS m/e (FIA+) 391, m/e (FIA-) 389;1H NMR (500 MHz, DMSO-d6) d 10,0 (Shir. s, 1H), 9,38 (Shir. m, 1H), 7.7 (d, 2H), 7,63 (d, 2H), 7,63 (d, 2H), was 7.36 (t, 2H), 7,27 (t, 2H), was 7.08 (t, 1H), to 6.88 (t, 1H), 6,77 (s, 1H), and 2.6 (s, 3H) ppm

1-(2-Methanesulfonyl-6-phenylaminopyrimidine-4-yl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine

To 1-(2-methylsulfanyl-6-phenylaminopyrimidine-4-yl)-N3-phenyl-1H-[1,2,triazole-3,5-diamine (240 mg; of 0.615 mmol) in 10 ml of p-dioxane and 10 ml of THF add 77% mCPBA (413 mg; 2.4 mmol). The reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture is quenched in water. The formed solid substance produce by filtration with suction and the solid is washed again with water. The solid is transferred into a round bottom flask with acetonitrile and the solvent is removed under reduced pressure. The resulting solid is triturated with MTBE and the solid is collected by filtration with suction and air-dried, thus obtaining 214 g not quite white powder (yield 82.3 per cent).

MS m/e (FIA+) 423, m/e (FIA-) 421;1H NMR (500 MHz, DMSO-d6) δ of 10.4 (s, 1H), 9,25 (s, 1H), 7,72 (s, 1H), 7,13 (t, 4H), 7,43 (t, 2H), 7,25 (m, 2H), 7,15 (t, 1H), 7,03 (s, 1H), 6,85 (t, 1H), 3,3 (s, 3H) ppm

4-(5-Amino-3-phenylamino-[1,2,4]triazole-1-yl)-6-phenylaminopyrimidine-2-carbonitril

To a solution of 1-(2-methanesulfonyl-6-phenylaminopyrimidine-4-yl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine (50 mg; 0.12 mmol) in 2 ml of DMSO added 8 mg (0.13 mmol) of potassium cyanide and the reaction mixture is stirred for 1 hour at ambient temperature. The solvent is removed under reduced pressure. The residue is triturated with water and the solid is allocate by filtration with suction. Column chromatography (SiO2with 5% EtOH-CH2 Cl2) followed by rubbing with diethyl ether gives 5 mg not quite white powder (yield 11%).

MS m/e (FIA+) 370, m/e (FIA-) 368;1H NMR (500 MHz, DMSO-d6) δ of 10.25 (s, 1H), 9,25 (s, 1H), 7,63 (m, 6N), and 7.4 (t, 2H), 7,25 (m, 2H), 7,15 (t, 1H), 7,07 (s, 1H), to 6.88 (t, 1H) ppm

Amide 4-(5-Amino-3-phenylamino-[1,2,4]triazole-1-yl)-6-phenylaminopyrimidine-2-carboxylic acid

To 4-(5-amino-3-phenylamino-[1,2,4]triazole-1-yl)-6-phenylaminopyrimidine-2-carbonitrile (20 mg; 0,054 mmol) in 500 μl of DMSO added at ambient temperature To anhydrous2CO3(5 mg; being 0.036 mmol), followed by adding 10 drops of 30% aqueous H2About2. The reaction mixture was stirred for 10 min and quenched with water. The aqueous layer was extracted with EtOAc (2x). The organic fractions are combined and washed with water, saturated salt solution and then dried (Na2SO4), filtered and concentrated. The solid is triturated with hot 2-propanol, leave to cool and the solid is collected by filtration with suction, washed with 2-propanol and MTBE and dried in the air, while receiving no white powder (yield 61%).

MS m/e (FIA+) 388, 410 (M+Na), m/e (FIA-) 386;1H NMR (500 MHz, DMSO-d6) δ 10,0 (Shir. s, 1H), and 9.2 (s, 1H), 7,83 (d, 4H), to 7.68 (d, 2H), 7,63 (d, 2H), and 7.4 (t, 2H), 7.23 percent (t, 2H), and 7.1 (t, 1H), 6,85 (t, 1H) ppm

4-(5-Amino-3-phenylamino-[1,2,4]triazole-1-yl)-6-phenylamino-1H-pyrimido the-2-he

1-(2-Methanesulfonyl-6-phenylaminopyrimidine-4-yl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine (12 mg, 0,028 mmol) was stirred at ambient temperature in 500 ml of DMF with 200 μl of 1 N. NaOH for 2 hours. The reaction mixture was quenched with water and the solution is allowed to form the precipitate. The filtrate is decanted and the solid is again suspended in water, give him a chance to settle and again decanted. The solid is transferred into a round bottom flask with acetonitrile and the solvent removed under reduced pressure. The resulting material, beige-yellow solid, is obtained in a yield of 90%.

MS m/e (FIA-) 359;1H NMR (500 MHz, DMSO-d6) δ 10,5 (Sirs, 1H), 9.15, with (s, 1H), 7,9 (Sirs, 2H), 7,66 (d, 4H), to 7.4 (t, 2H), 7,2 (t, 2H), 7,18 (Sirs, 1H), 6,8 (t, 1H), 6.35mm (Sirs, 1H) ppm

1-(2-Methoxy-6-phenylaminopyrimidine-4-yl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine

1-(2-Methanesulfonyl-6-phenylaminopyrimidine-4-yl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine (12 mg, 0,028 mmol) was stirred at ambient temperature in 500 μl DMF with 200 ál their solution of sodium methoxide for 2 hours. The reaction mixture was quenched with water and the precipitate provide an opportunity to disembark from the solution. The filtrate is decanted and the material washed with water, again decanted and the solid is transferred into a round bottom flask with acetonitrile and rastvoritelem.dl under reduced pressure. Preparative HPLC (gradient eluent: acetonitrile-water with 0.1% TFA) to give 12 mg of beige solid, yield 90%.

MS m/e (FIA+) 375;1H NMR (500 MHz, DMSO-d6) δ of 9.8 (s, 1H), 9.15, with (s, 1H), and 7.7 (m, 7H), 7,37 (t, 2H), 7,25 (m, 2H), 7,02 (t, 1H), 6,83 (t, 1H), only 6.64 (s, 1H) ppm

6-[5-Amino-3-phenylamino-[1,2,4]triazole-1-yl)-N2-ethyl-N2-methyl-N4-phenylpyrimidine-2,4-diamine

1-(2-Methanesulfonyl-6-phenylaminopyrimidine-4-yl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine (75 mg, 0.18 mmol) was stirred with N-ethylmethylamine (200 μl; 1.5 mmol) in 1 ml THF in a sealed tube for 10 hours at 80°C. the Reaction mixture was quenched with 1 N. HCl and the resulting precipitate is centrifuged to obtain a precipitate. The precipitate is suspended in water and again centrifuged to obtain a precipitate. Preparative HPLC (gradient eluent: acetonitrile-water with 0.1% TFA) gives specified in the header connection. The purified material is converted into the HCl salt by addition of 1 N. HCl, and the solvent is removed under reduced pressure. The material was obtained in the form of not-quite-white solid (5 mg, yield 6%).

MS m/e (FIA+) 402, m/e (FIA-) 400;1H NMR (500 MHz, DMSO-d6) δ 9,45 (Sirs, 1H), 9,05 (Sirs, 1H), 7.7 (d, 2H), 7,65 (Sirs, 2H), to 7.61 (d, 2H), 7,35 (m, 2H), 7,25 (m, 2H), 6,97 (t, 1H), 6,85 (t, 1H), 6,33 (s, 1H), 3,6 (Shir. quart., 2H), 3,1 (Shir. s, 3H)and 1.15 (t, 3H) ppm

Scheme 30

Reaction conditions: A. piperazine, NMP, 220°C, 6 min; Century harangued the ID acid, the basis Hunya, CH2Cl2.

Example 66

N3-Phenyl-1-(6-piperazine-1-Yeremey-4-yl)-1H-[1,2,4]triazole-3,5-diamine

To a solution of 200 mg of 1-(6-chloropyrimidine-4-yl)-N3-phenyl-1H-[1,2,4]triazole-3,5-diamine (0.69 mmol, 1 EQ.) in 5 ml of NMP added 200 mg of piperazine (2.32 mmol, 3.3 EQ.). The reaction vessel is sealed and heated to 220°by microwave irradiation for 6 min and leave to cool. The resulting solution was poured into 50 ml water and the precipitate filtered and washed with water (3 x 20 ml). The resulting waxy solid (150 mg) is used without further purification.

LC-MS: Rf=1,35 min, 338,24 (M+H).

Example 67

3-{4-[6-(5-Amino-3-phenylamino-[1,2,4]triazole-1-yl)pyrimidine-4-yl]piperazine-1-yl}-3-oxopropionate. To a stirred solution of 100 mg of 2-tsianuksusnogo acid (1.2 mmol, 7.9 equiv.) in 10 ml of CH2Cl2add sequentially 300 μl of oxalicacid (435 mg, of 3.45 mmol, 23 EQ.) and 1 drop of DMF. The reaction mixture is left to stir at 25°s to stop shedding vesicles. The reaction mixture was concentrated and subjected to azeotropic distillation with CH2Cl2(3 × 10 ml) before re-dissolving in 10 ml of CH2Cl2. To this solution was added 50 mg N3-phenyl-1-(6-piperazine-1-Yeremey-4-and the)-1H-[1,2,4]triazole-3,5-diamine (0,148 mmol, 1 EQ.) in 5 ml of CH2Cl2. After adding 200 ál of base Hunga the reaction mixture was stirred for 12 h at 25°C. the Reaction mixture was then concentrated and purified by chromatography on silica gel, thus obtaining a 2.9 mg (0,007 mmol, yield 5%).

LC-MS: 2,72 min/405,2 (M+H). 1H NMR (500 MHz, CDCl3) δ 8,31 (1H, s), 7,40 (2H, d), 7,25 (2H, t), 6,89 (1H, t), 6,77 (1H, s), of 6.65 (2H, Sirs), of 6.45 (1H, s), 3,82 (2H, m), 3,70 (4H, m), 3,52 (2H, m), 3,40 (2H, s) ppm

Scheme 31

(a)2CO330% of the H2About2, DMSO

5-(5-Amino-3-phenylamino-[1,2,4]triazole-1-yl)-2-methoxybenzamide. To a stirred solution of 5-(5-amino-3-phenylamino)-[1,2,4]triazole-1-yl)-2-methoxybenzonitrile (20 mg, 0,065 mmol) and K2CO3(2 mg) in DMSO (0.3 ml) at room temperature add 30% aqueous solution of N2About2(0.3 ml). After 1 hour add a further 30% aqueous H2About2(0.15 ml). After 40 min, water is added together with 5% aqueous Na2CO3and the mixture is stirred for several minutes. The solid is collected and washed with several portions of water and dried under vacuum, thus obtaining white solid (18 mg, to 0.055 mmol, yield 85%).

1H NMR 500 MHz (DMSO) 8,82 (s, 1H), to 7.93 (d, 1H), 7,71 (Shir. s, 1H), 7,63 (DD, 1H), 7,60 (Shir. s, 1H), 7,52 (d, 2H), 7,25 (d, 1H), 7,19 (t, 2H), 6.75 in (t, 1H), 6,28 (Shir. s, 2H), 3,93 (s, 3H), ppm LC/MS: Rt=2,27 min, (M+N)= 325,2.

Scheme 32

(2-Chloropyridin-4-yl)hydrazine

2-Chloropyridin-4-ylamine (2 g, 15.6 mmol) was dissolved in 20 ml of 1 M HCl and 4 ml conc. HCl and cooled to 0°C. sodium Nitrite (1 g, 17 mmol) dissolved in 2 ml of water and the solution added dropwise to a solution of pyridine. The mixture is stirred at 0-5°C for 2 h and then added dropwise to the suspension SnCl2in 35 ml conc. HCl at 0°C. the Mixture was stirred at 0°C for 1 hour, then the pH is carefully raised to pH 9-10 with NaOH using efficient cooling and stirring. The aqueous mixture is extracted with a 10% solution of the Meon/chloroform and the organic layer is separated, dried (sodium sulfate) and evaporated. The crude product mixture is purified column chromatography (silica, 5% Meon/DCM)to give 400 mg (2-chloropyridin-4-yl)hydrazine. MS ES+ 144, 0MM, 146,3.

Diametrical, 1-(2-chloropyridin-4-yl)-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine and other diametrically described in the schema and the table is obtained from (2-chloropyridin-4-yl)hydrazine and imidate esters using procedures described elsewhere in this invention.

5-[2-(4-Methylpiperazin-1-yl)pyridine-4-yl]-N2-(4-(morpholine-4-ylphenyl)-5H-imidazole-2,4-diamine. 1-(2-chloropyridin-4-yl)-N3-(4-(morpholine-4-ylphenyl)-5H-imidazole-2,4-diamine (100 mg, 0.27 mmol) and N-methylpiperazine (101 mg, 1 mmol) is mixed B1 ml of n-butanol and heated to 230° C for 360 seconds in a personal microwave instrument. The solvent is evaporated in vacuo and the residue purified preparative TLC (1% NH4OH/10% Meon/DCM), while receiving 45 mg 5-[2-(4-methylpiperazin-1-yl)pyridine-4-yl]-N2-(4-(morpholine-4-ylphenyl)-5H-imidazole-2,4-diamine.

In a similar way we obtain the following connections.

The structure's nameMSNMR
5-[2-(4-Methylpiperazin-1-yl)pyridine-4-yl]-N2-(4-(morpholine-4-ylphenyl)-5H-imidazole-2,4-diamine433,3CD3CN: is 7.9 (d, 1H), 7.5 (d, 2H), and 7.1 (m, 3H), at 3.9 (m, 4H), of 3.75 (m, 2H), 3,25 (m, 2H), 3,2 (m, 4H), and 2.8 (s, 6H)
1-[2-(2-Diethylaminoethylamine)-pyridin-4-yl]-N3-(4-(morpholine-4-ylphenyl)-1H-[1,2,4]triazole-3,5-diamine424,5DMS-d6: 9,8 (Sirs, lH), cent to 8.85 (Sirs, 1H), and 8.2 (d, lH), 7.5 (d, 2H), 7,0 (d, lH), to 6.95 (s, 1H), 6.90 to (m, 2H), 6,7 (Sirs, 2H), 4,45 (m, 2H, in), 3.75 (m, 4H), 3,5 (m, 2H), 3,2-3,0 (m, 8H), 2,85 (s, 3H)
N3-(3-Isopropoxy-4-morpholine-4-ylphenyl)-1-[2-(4-methylpiperazin-1-yl)pyridine-4-yl]-1H-[1,2,4]triazole-3,5-diamineof 494.5DMSO-d6: is 8.75 (s, 1H), 8,10 (d, 1H), 7,40 (s, 1H), 6,95 (d, 1H), 6.90 to (d, 1H), 6,85 (s, lH), to 6.75 (d, 1H), 6,60 (Sirs, 2H), 4,50 (m, 1H), 3,70 (m, 4H), to 3.50 (m, 4H), 2,90 (m, 4H), 2.40 a (m, 4H), 2,22 (s, 3H), to 1.32 (d, 6H)

Example 68

N3-Benzo[1,3]dioxol-5-yl-1-pyrimidine-4-yl-1H-[1,2,4]triazole-3,5-diamine. N3-Benzo[1,3]is oxol-5-yl-1-(6-chloropyrimidine-4-yl)-1H-[1,2,4]triazole-3,5-diamine (40 mg, 0.12 mmol) is stirred with 10% Pd/C in 1 ml ethanol under 1 ATM of hydrogen for 18 hours. The catalyst was removed by filtration and the solvent is evaporated. The crude product is purified preparative HPLC, while receiving 11 mg N3-benzo[1,3]dioxol-5-yl-1-pyrimidine-4-yl-1H-[1,2,4]triazole-3,5-diamine in the form of the TFA salt.

1H NMR (acetone-d6: 8,9 (s, 1H), and 8.8 (d, 1H), 8,1 (Sirs, 1H), and 7.4 (m, 3H), and 7.1 (d, 1H), 6,8 (d, 1H), 5,9 (s, 2H).

In a similar way we obtain the following connection:

NameMS (M+N)HPLC, method a1H NMR
N3-(4-(Morpholine-4-ylphenyl)-1-pyrimidine-4-yl-1H-[1,2,4]triazole-3,5-diamine339,401,60DMSO-d6: 8,95 (s, lH), of 8.90 (s, lH), 7,8 (Sirs, 2H), 7,6 (s, lH), 7.5 (d, 2H), 6,9 (d, 2H, in), 3.75 (m, 4H), 3.0 a (m, 4H)

2-(3,4-Dimethoxyphenylthio)-4H-[1,2,4]triazolo[1,5-a]hinzelin-5-Oh and 2-amino-4-(3,4-acid)-4H-[1,2,4]triazolo[1,5-a]hinzelin-5-he

A solution of 1-(3,4-acid)-3-cyano-2-phenylazomethine (600 mg, 2 mmol), hydrochloride of 2-hydrazinobenzene acid (760 mg, 4 mmol) and triethylamine (1.6 ml) in isopropanol (20 ml) and heated to boiling under reflux for 24 hours. The mixture is evaporated. The residue is suspended in water (50 ml), filtered. The solid is purified HPLC, thus obtaining 2-(3,4-dimethoxyphenyl the laminitis)-4H-[1,2,4]triazolo[1,5-a]hinzelin-5-he (263 mg) and its isomer (72 mg). Data 2-(3,4-dimethoxyphenylthio)-4H-[1,2,4]triazolo[1,5-a]hinzelin-5-it: FIA-MS; m/e=338,2 (M+H), (336,1 (M-H). Rt=3,09 min (method A).1H NMR (500 MHz, DMSO-d6): 12,90 (s, 1H), 9,36 (s, 1H), 8,15 (d, 1H), to $ 7.91 (t, 1H), 7,86 (d, 1H), 7,45 (t, 1H), 7,41 (d, 1H), 7,18 (DD, 1H), 6.90 to (d, 1H), 3,80 (s, 3H), 3,71 (s, 3H). Data2-amino-4-(3,4-acid)-4H-[1,2,4]triazolo[1,5-a]hinzelin-5-she: LC-MS; m/e=338,2 (M+H), (336,1 (M-H). Rt=2,34 min1H NMR (500 MHz, DMSO-d6): 8,17 (d, 1H), of 7.90 (t, 1H), 7,76 (d, 1H), 7,45 (t, 1H), 7,16 (d, 1H), to 7.09 (d, 1H), 7,02 (DD, 1H), 6,04 (s, 2H), 3,82 (s, 3H), 3,70 (s, 3H).

(4,5-Dihydro-[1,2,4]triazolo[1,5-a]hinzelin-2-yl)-(3,4-acid)Amin

A suspension of 2-(3,4-dimethoxyphenylthio)-4H-[1,2,4]triazolo[1,5-a]hinzelin-5-it (57 mg) in phosphorus oxychloride (5 ml) is heated at 90°C for 2 hours. The mixture is evaporated. The residue is suspended in dichloromethane, washed with cold sodium bicarbonate, saturated salt solution and dried (Na2SO4). Filtration and concentration gives the crude (5-chloro-[1,2,4]triazolo[1,5-a]hinzelin-2-yl)-(3,4-acid)amine (68 mg). LC-MS: m/e=356,1 (M+H).

When 0°With a solution of sodium borohydride (2.0 M, 0.25 ml) are added to a solution of the above chloride (38 mg, 0,107 mmol) in chloroform (5 ml) and ethanol (2 ml) (or DMF) and Meon). The reaction mixture was kept at room temperature for 1 hour (monitoring conduct analytical HPLC), acidified with triperoxonane acid and cleansing the t HPLC, while receiving specified in the title compound (12 mg). FIA-MS: m/e=324,1 (M+H). Rt=is 3.08 (method A).1H NMR (500 MHz, DMSO-d6): 8,90 (s, 1H), 7,71 (s, 1H), 7,39 (d, 1H), 7,34 (t, 1H), 7,31 (DD, 1H), 7,25 (d, 1H), 7,12 (DD, 1H), was 7.08 (TD, 1H), at 6.84 (d, 1H), 4,50 (s, 2H), of 3.77 (s, 3H), 3,68 (s, 3H).

Similarly receive the following connections:

NameMS (M+N)The HPLC retention time (min), fashion And1H NMR
(4,5-Dihydro[1,2,4]triazolo[1,5-a]-hinzelin-2-yl)-(3,5-acid)Amin324,23,32DMSO-d6: to 7.99 (d, 1H), 7,94 (width,s, 1H, NH), 7,43 (width,s, 1H, NH), 7,34 (d, 2H), 7,26 (d, 1H), 7,11 (DDD, 1H), 6,63 (d, 1H), is 6.54 (DD, 1H), 4.53-in (s, 2H), 3,85 (s, 3H), 3,74 (s, 3H)
(4,5-Dihydro[1,2,4]triazolo-[1,5-a]-hinzelin-2-yl)phenylamine347,12,71DMSO-d6: 9,15 (s, 1H), 7,73 (s, 1H), 7.62mm (d, 2H), was 7.36 (m, 2H), 7,25 (m, 3H), 7,10 (DDD, 1H), for 6.81 (t, 1H), 4,51 (s,2H)
(4,5-Dihydro[1,2,4]triazolo-[1,5-a]-hinzelin-2-yl)-(4-(morpholine-4-ylphenyl)Amin349,12,71DMSO-d6: cent to 8.85 (s, 1H), 7,68 (s, 1H), 7,51 (d, 2H), 7,32 (m, 2H), 7,25 (d, 1H), was 7.08 (TD, 1H), to 6.88 (d, 2H), 4,50 (s, 2H, in), 3.75 (m, 4H), 2,98 (m, 4H)

Scheme 33

Reagents: (a) (PhO)2CN(CN), iPrOH; 75°With; (b) of hydrazine monohydrate, iPrOH, 70°With; (c) Im2CS, imidazole, DMF, room temperature, then Ani is in, 0°With; (d) Br2, DMF, room temperature.

On the above diagram 33 shows a General way to obtain some 6-substituted triazolobenzodiazepine, where R is an ether group or the amino group.

Example 69

4-(3-Cyano-2-finelytuned)benzosulfimide. 4-Aminobenzenesulfonamide (2 mmol) is added in one portion to a solution of Diphenoxylate (2 mmol) in isopropanol. The reaction mixture was stirred at 75°C for 4 hours. The reaction mixture then allow to cool to room temperature. Formed solid precipitate is filtered off. It is washed with isopropanol, thus obtaining specified in the title compound (0.33 g; yield 70%).

1H NMR (400 MHz, DMSO-d6) δ 7,30-7,40 (5H, m), 7,45 is 7.50 (2H, t), 7,65-of 7.70 (2H, d), 7,80-a 7.85 (2H, d), 11,20 (1H, s); MS (ES+) m/e=317.

Example 70

4-(5-Amino-1H-[1,2,4]triazole-3-ylamino)benzosulfimide. To a solution of 4-(3-cyano-2-finelytuned)benzosulfimide (1.35 mmol) in THF (5 ml) add a solution of hydrazine monohydrate (2 mmol; 1.5 equivalents). The solution was stirred at 70°C for 16 hours. The reaction mixture allow to cool to room temperature. Precipitated white solid. It is separated by filtration and washed with ethanol, thus obtaining the criminal code is related to the title compound (300 mg; yield 87%).1H NMR (400 MHz, DMSO-d6) δ 5,95-6,00 (2H, s), 7,00-7,05 (2H, s), 7,55-the 7.65 (4H, m), 9,15-to 9.20 (1H, s); MS (ES+) m/e=255.

Example 71

(4-Phenoxyphenyl)amide 5-amino-3-(4-sulfhemoglobinemia)-[1,2,4]triazole-1-Topolino acid. Thiocarbonyldiimidazole high (0.56 mmol, 1.5 equivalents) are added to a solution of 4-phenoxyimino (0.6 mmol, 1.6 equivalents) and imidazole (0.07 mmol, 0.2 equivalent) in acetonitrile (5 ml). The reaction mixture was stirred at room temperature for three hours. As one portion add 4-(5-amino-1H-[1,2,4]triazole-3-ylamino)benzosulfimide (0,37 mm, 1 equivalent). The reaction mixture was stirred at 50°C for 16 hours. After addition of DMF (1 ml) the reaction mixture was stirred at 80°C for one hour. The reaction mixture was concentrated in vacuo. The residue is purified by chromatography on silica gel with elution with a mixture of EtOAc:pentane (30:70 to 0:100), while receiving specified in the title compound (40 mg, yield 40%).1H NMR (400 MHz, DMSO-d6) δ 7,05-7,18 (6N, m), 7,20-of 7.23 (1H, t), 7,40-to 7.50 (4H, m), 7,70 to 7.75 (2H, d), 7,80-a 7.85 (2H, d), 8,45-of 8.50 (2H, s), 9,80-9,85 (1H, s)10,90 (1H, s); MS (ES+) m/e=482.

Example 72

4-[5-Amino-1-(6-phenoxybenzamine-2-yl)-1H-[1,2,4]triazole-3-ylamino]benzosulfimide. Bromine (7 μl, 1 equivalent) is added to a stirred suspension of (4-phenoxyphenyl)amide 5-amine is-3-(4-sulfhemoglobinemia)-[1,2,4]triazole-1-Topolino acid in dichloromethane (3 ml). The reaction mixture was stirred at room temperature for 18 hours. Then add a solution of bromine (7 μl) in acetic acid (1 ml) to bring the reaction to completion, the reaction mixture is stirred for an additional four hours. The precipitated white solid was separated by filtration, thus obtaining specified in the title compound (5 mg, yield 7%).

1H NMR (400 MHz, DMSO-d6) δ 7,05-7,20 (8H, m), 7,35 is 7.50 (4H, m), 7,70 to 7.75 (2H, d), 7,80-a 7.85 (2H, d), 9,90-9,95 (1H, s); MS (ES+) m/e=480.

Scheme 34

Reagents: (a) NH3Hcl , EtOH, 90°With, then benzothiazol-2-ilkerin, NMM, 110°; RCOCl, pyridine.

In the above diagram 34 shows a General way to obtain N-(5-amino-1-benzothiazol-2-yl-1H-[1,2,4]triazole-3-yl)amides.

Example 73

1-Benzothiazol-2-yl-1H-[1,2,4]triazole-3,5-diamine. To a suspension of Diphenoxylate (2 mmol) in ethanol (3 ml) in a sealed flask is added 2 M solution of ammonia in ethanol (4 mmol). The reaction mixture was stirred at 90°C for 48 hours, then concentrated in vacuo. The residue is dissolved in N-methylmorpholine (5 ml). To this solution add benzothiazol-2-ilkerin (2 mmol). The reaction mixture was stirred at 110°C for 24 hours. After cooling, to the reaction mixture add distilled water (20 ml) and the mixture of races is Radelet between ethyl acetate and saturated salt solution (100 ml/100 ml). At this stage, the solid is removed by filtration. This white solid was washed with more ethyl acetate and dried under vacuum, thus obtaining the net specified in the title compound (170 mg, yield 37%).1H NMR (400 MHz, DMSO-d6) δ to 5.85 (2H, s), 7,30-to 7.35 (1H, t), 7,45 is 7.50 (1H, t), 7,60 (2H, s), 7,80-a 7.85 (1H, d), 7,98-8,02 (1H, d). MS (ES+) m/e=233.

Example 74

N-(5-Amino-1-benzothiazol-2-yl-1H-[1,2,4]triazole-3-yl)benzamide. The benzoyl chloride (0.34 mmol) is added dropwise to a stirred solution of 1-benzothiazol-2-yl-1H-[1,2,4]triazole-3,5-diamine (0.34 mmol) in pyridine (3 ml). The reaction mixture was stirred at room temperature for 2 hours, then concentrated in vacuo. The residue is distributed between ethyl acetate and 10% aqueous citric acid. At this stage, the filtered white solid. The solid is dried under vacuum, thus obtaining the net specified in the title compound (10 mg; yield 15%).1H NMR (400 MHz, DMSO-d6) δ 7,40 was 7.45 (1H, t), 7,50-of 7.70 (3H, m), a 7.85-8,00 (6N, m)and 8.1 (1H, d), 10,95 (1H, s). MS (ES+) m/e=337.

Scheme 35

Example 75

Phenyl-(3-pyridyl)-N-cyanocarbonimidate. To a solution of diphenyl-N-cyanocarbonimidate (of 1.85 mmol) in tert-butanol (4 ml) is added 3-aminopyridine (of 1.85 mmol) and the mixture heated to boiling under reflux in ECENA 3 hours. After cooling to room temperature, the resulting white precipitate is collected by filtration under reduced pressure and washed with a small amount of cold Et2O, then dried in vacuum at 40°C for 3 hours, while receiving specified in the header connection (to 0.23 g, 54%).1H NMR (400 MHz, DMSO-d6) δ 7,33 (3H, m), to $ 7.91 (1H, d), 8,43 (1H, d), 8,67 (1H, s), 10,99 (1H, s); MS (ES+) m/e=239,2 (100%).

Example 76

N3-(3-Pyridyl)-1H-[1,2,4]triazole-3,5-diamine. To a solution of phenyl-(3-pyridyl)-N-cyanocarbonimidate (1.00 mmol) in isopropanol (10 ml) is added hydrazine hydrate (1 mmol) and the mixture is heated to boiling under reflux for 2.5 hours. After cooling to room temperature, the resulting white precipitate is collected by filtration under reduced pressure and washed with a small amount of cold isopropanol, then dried in vacuum at 40°C for 6 hours, while receiving specified in the title compound (0.15 g, yield of 87.5%).1H NMR (400 MHz, DMSO-d6) δ to 5.93 (2H, s), 7,17 (1H, m), 7,94 (2H, m)8,64 (1H, d), 8,88 (1H, s), 11,24 (1H, s); MS (ES+) m/e=177,2 (100%).

Example 77

Phenylamide 5-amino-3-(3-pyridylamino-[1,2,4]triazole-1-carboxylic acid. To a solution of N3-(3-pyridyl)-1H-[1,2,4]triazole-3,5-diamine (0.43 mmol) in dry THF (3 ml) and dry DCM (3 ml) is added dropwise to finalization the (0.43 mmol) over 1 minute and the mixture is stirred at room temperature for 2 hours. The reaction mixture was concentrated in vacuo and the residue purified column chromatography [silica Merck, elution EtOAc and hexane (4:1)], while receiving specified in the header connection (22,0 mg, 17%).1H NMR (400 MHz, DMSO-d6) δ 7,17 (1H, t), 7,28 (1H, m), 7,39 (4H, m), the 7.65 (2H, d), of 8.09 (1H, m), 8,23 (1H, m), 8,79 (1H, d), 9,44 (1H, s), for 9.64 (1H, s); MS (ES+) m/e=296,3 (100%).

Additional data for compounds of the invention:

td align="center"> I-698 323,3
Connection1H NMRM+1 (OBS.)
I-6923,71 (3H, s), 6.89 in (2H, d), 7,37 (1H, t), 7,51 (3H, m), 7,78 (2H, s), 7,86 (1H, d), of 8.06 (2H, s), 9,20 (lH, s)339,2
I-6932,04 (3H, s), to 7.09 (1H, d), 7,17 (1H, t), of 7.36 (1H, t), 7,38 (1H, t), 7,42 (1H, t), of 7.70 (1H, s), 7,81 (2H, s), 7,87 (1H, d), 8,07 (1H, d), 9,40 (1H, s), 9,86 (lH,s)366,3
I-6943,61 (3H, s), of 3.80 (6H, s),? 7.04 baby mortality (2H, s), 7,37 (1H, t), 7,51 (1H, t), 7,80 (2H, s), 7,87 (1H, d), 8,07 (1H, d), 9,31 (1H, s)399,3
I-695a 2.01 (3H, s), 7,35 (1H, t), 7,47 (5H, m), 7,80 (2H, s), 7,87 (1H, d), with 8.05 (1H, d), was 9.33 (1H, s), 9,78 (1H, s)366,2
I-6966,33 (1H, s), 7,27 (3H, m), 7,35 (1H, t), of 7.48 (1H, t), to 7.77 (2H, s), to 7.84 (1H, d), of 7.90 (1H, s), 8,07 (1H, d), which is 9.09 (1H, s), 10,88 (1H, s)348,3
I-6976,30 (1H, m), 7,03 (2H, d), 7,07 (1H, t), 7,37 (1H, t), of 7.48 (1H, t), 7,79 (2H, s), 7,87 (1H, d), 8,07 (1H, d), a 9.25 (1H, s), to 9.32 (1H, s)325,3
of 3.78 (3H, s), 6,46 (1H, DD), was 7.08 (1H, m), 7,17 (1H, t), 7,38 (1H, t), 7,40-7,41(1H, m), 7,49 (1H, t), of 7.82 (2H, Sirs), 7,86 (1H, d), 8,07 (1H, d),9,43 (1H, s)339
I-6993,88 (3H, s), 7,38-7,51 (5H, m), 7,87-7,89 (3H, m), of 8.09 (1H, d), 8,31 (1H, s), 9,71 (1H, s)367
I-7007,38 (1H, t), 7,52 (1H, t), 7,66 (1H, d), 7,86-7,93 (6H, m), 8,08 (1H, d), 9,94 (1H, s), 12,55 (1H, Sirs)353
I-701of 3.46 (3H, s), was 7.08 (1H, t), 7,35 (3H, t), 7,49 (3H, m), 7,82 (2H, s), 7,86 (1H, d), of 8.04 (1H, s)323,3
I-702to 7.18 (1H, d), 7,40 (1H, t), to 7.50 (1H, t), 7,58 (1H, d), of 7.90 (4H, m), 8,49 (1H, s)8,64 (1H, d), being 9.61 (1H, s), 12,81 (1H, s)349,3
I-703a 3.01 (4H, m), and 3.72 (4H, m)6,91 (2H, d), 7,37 (1H, t), 7,49 (3H, m), 7,78 (2H, s), 7,86 (1H, d), of 8.06 (1H, d), to 9.15 (1H, s)394,3
I-704of 1.47 (9H, s), 7,37 (4H, m), of 7.48 (4H, m), 7,79 (2H, s), 7,86 (1H, d), with 8.05 (1H, d), 9,12 (1H, s), 9,26 (1H, s)424,3
I-7053,62 (3H, s), with 3.79 (6H, s), 7,03 (2H, s), 7,38 (2H, m), to 7.67 (1H, m), of 7.75 (3H, m), which 9.22 (1H, s)383,29
I-7063,63 (3H, s), 3,76 (6H, s)5,80 (1H, s), 6,55 (1H, s), 7,25 (2H, m), the 7.43 (1H, Shir. C)to 7.59 (1H, d), 7,98 (1H, Shir. C)8,44 (1H, d)382,32
I-7073,61 (3H, s), a-3.84 (6H, s), 7,00 (2H, s), 7,18 (2H, m), 7,47 (1H, m), 7,56 (1H, m), of 7.70 (1H, s), of 9.02 (1H, s), and 12.4 (1H, Shir. C)382,31
I-7085,95 (2H, s), 6,85 (1H, d), 7,01 (1H, d.o.d.), 7,33 (1H, d), 7,37 (1H, t), 7,49 (1H, t), 780 (2H, C)7,86 (1H, d), of 8.04 (1H, d), 9,31 (1H, s)353,3
I-7096,51(1H, d), 7,39 (1H, t), 7,53 (1H, t), of 7.70 (5H, m), 7,86 (2H, s), 7,88 (1H, s), 8,08 (1H, d) 8,39 (1H, d), 9,62 (1H, s)375,3
I-710was 7.08 (1H, s), 7,37 (1H, t), 7,51(3H, t), 7,54 (2H, d), 7,66 (1H, s), of 7.70 (2H, d), 7,86 (2H, s), 7,88 (1H, s), 8,08 (1H, d), of 8.15 (1H, s), 9,65 (1H, s)375,3
I-7117,37 (1H, t), 7,49 (1H, t), to 7.77 (2H, d), 7,89 (3H, m), 8,18 (3H, m), to 9.45 (1H, s), 9,76 (1H, s)to 393.3
I-712with 4.64 (2H, s), is 6.61 (2H, d), 7,26 (2H, d), 7,39 (1H, t), of 7.48 (1H, t), 7,72 (2H, s), to 7.93 (1H, d), of 8.04 (1H, d), 8,86 (1H, s)324,3
I-7137,33-7,38 (2H, m), of 7.48-7,52 (2H, m), of 7.75 (1H, d), 7,88 (1H, d), to 7.93 (2H, Shir. with),of 8.06 (1H, m), 8,10 (1H, d),9,92 (1H, s),334
I-714to 6.88 (1H, t), 7,28 (2H, t), of 7.36 (1H, t), 7,51 (1H, t), to 7.59-to 7.61 (2H, m), 7,83 (2H, Shir. C)7,86 (1H, d), of 8.06 (1H, d), to 9.45 (1H, s)309
I-715and 2.79 (3H, s), 7,30 (1H, d), 7,33-7,39 (2H, m), 7,51 (1H, t), 7,78 (1H, m), 7,86-7,88 (4H, m), of 8.00 (1H, s), 8,08 (1H, d), to 8.45 (1H, d), to 9.57 (1H, s)366
I-716of 2.97 (3H, Shir. C)a 3.01 (3H, Shir. C)6,89 (1H, d), 7,31-7,37 (2H, m), 7,51(1H, t), 7,63-to 7.64 (3H, m), 8,08 (1H, d), a 9.60 (1H, s)380
I-717was 4.42 (2H, d), 5,02 (1H, t), 7,22 (2H, d), of 7.36 (1H, t), of 7.48 (1H, t), of 7.55 (2H, d), 7,82 (2H, Shir. C)7,86 (1H, d), of 8.06 (1H, d), 9,39 (1H, s)339
I-7187,06 (1H, t), 7,26 (1H, t), 7,35-7,40 (2H, m), 7,51 (1H, t), 7,71 (1H m), 7,87 (2H, m), of 8.09 (1H, d), 9,67 (1H, Shir. C)12,50 (1H, acsis)387
I-7194,47 (2H, d), of 5.15 (1H, t), at 6.84 (1H, d), of 7.23 (1H, t), of 7.36 (1H, t), 7,49-7,52 (3H, m), 7,82 (2H, Shir. C)7,86 (1H, d), 8,07 (1H, d), 9,40 (1H, s)339
I-7201H NMR (CDCl3) 3,24 (3H, d J 5,01 Hz)to 3.89 (3H, s), was 4.02 (3H, s), 6,63 (1H, W), for 6.81-to 6.88 (2H, m), 7,31-to 7.35 (1H, m), 7,45-7,49 (1H, m), EUR 7.57-7,58 (1H, m), 7,70-7,74 (1H, m), 7,80-to 7.84 (2H, m)383,24
I-7213,74 (3H, s), the 4.29 (2H, d, J=6.2 Hz), 6,77-PC 6.82 (1H, m), 6.90 to-7,01 (3H, m), 7,20-7,26 (1H, m), 7,29-to 7.35 (1H, m), 7,42-7,49 (1H, m), 7,68 (2H, Shir. C)7,79-7,81 (1H, m), 7,99 shed 8.01 (1H, m)353,18
I-7224,22 (2H, d, J=6.3 Hz), 5,98 (2H, s), 6,80-to 6.95 (4H, m), 7.29 trend and 7.36 (1H, m), 7,41-7,50 (1H, m), to 7.67 (2H, Shir. C), 7,80 (1H, d, J=8.0 Hz), 8,00 (1H, d, J=8.0 Hz)367,22
I-7233,71 (3H, s), 3,74 (3H, s), 4,24 (2H, d, J=6.2 Hz), 5,75-5,78 (1H, m), 6,84-6,91 (3H, m), 7,00-7,03 (1H, m), 7.29 trend and 7.36 (1H, m), 7,42-7,50 (1H, m), to 7.67 (2H, Shir. C)7,79-of 7.82 (1H, m), of 7.90-8,11 (1H, m)383,23
I-7243,62 (3H, s), 3,81(6N, (C), 7,03 (2H, s), 7,52 one-7,55 (1H, m), 7,81 - a 7.85 (3H, m), by 8.22 (1H, d), 9,34 (1H,s)433,16
I-7253,61 (3H, s), 3,81 (6N, (C), 7,03 (2H, s), 7,34-7,39 (1H, m), 7,78 (2H, s), a 7.85-7,88 (1H, m), 7,98 shed 8.01 (1H, m), to 9.32 (1H, s)417,24
I-726(CDCl3/CD3OD): 7,33 (1H, t), 7,46 (1H, t), a 7.62 (2H, m), 7,69 (2H, m), 7,82 (2H, t), 8,08 (1H, s), charged 8.52 (1H, s)376.3 on
I-7273,61 (3H, s), 3,81 (6H, s), and 3.2 (3H, C)? 7.04 baby mortality (2H, s), 7,07-7,10 (1H, m), 7.68 per-7,76 (4H, m), of 9.30 (1H, s)429,21
I-728(CDCl3) 3,85 is equal to 4.97 (6H, d), 6,45-of 6.50 (1H, DD), 6,50-6,55 (2H, s), 6,8-6,85 (1H, d), 7.3 to 7.4 (1H, t), 7,45 is 7.50 (1H, t), 7,8-7,9 (2H, m), and 8.0 (1H, s)369
I-729(CDCl3) to 1.25 (3H, s), of 3.97 (3H, s), 6,38-6.42 per (1H, s), 6,50-6,60 (3H, m), 7,05 (1H,d), 7,35-7,40 (1H, t), 7,45-to 7.50 ppm (1H, t), 7,8-7,9 (2H, m), and 8.0 (1H, s)353
I-7307,30-of 7.60 (6H, m), 7,82-of 7.90 (3H, m), 8,08 (1H, m),9,62 (1H, s)389,09
I-731of 3.60 (3H, s), of 3.77 (6H, s), is 4.21 (3H, s), 6,98 (2H, Shir. C), 7,26 (2H, m), to 7.59 (2H, m), 7,72 (2H, s), 9,12 (1H, Sirs)396,29
I-7323,53 (9H, m), of 6.20 (2H, s), at 6.84 (2H, s), 7,25 (7H, m), the 7.43 (1H, m), 7,60 (1H, m), 7,88 (2H, s), 9,18 (1H, s)472,42
I-733to 2.42 (3H, s), 3,61 (3H, s), 3,81 (6H, s),? 7.04 baby mortality (2H, Shir. C)to 7.32 (1H, d), 7,76 (3H, m), 7,86 (1H, s), of 9.30 (1H, s)413,31
I-734of 3.27 (3H, s), 3,62 (6H, s), 3,81 (6H, s), 7,06 (2H, s), of 7.90 (2H, Shir. C)8,02 (2H, m), 8,72 (1H, s), 9,40 (1H, s)477,28
I-735of 0.85-0.90 (4H, m), 2,01-2,05 (1H, m)and 3.59 (3H, s), 3,76 (6H, s), 6,93 (1H, s), 7,00 (2H, s), 7,41 (2H, s), 9,17 (1H, s)389,23
I-7366,95-7,05 (1H, m), 7,15-of 7.25 (2H, m), 7,32-7,40 (1H, t), 7,45-7,52 (1H, t), 7,8-7,9 (3H, m), 8,05-8,10 (1H, d), 8,10-to 8.14 (1H, t), and 9.0 (1H, s)326
I-7373,62 (3H, s), 3,81 (6H, s),? 7.04 baby mortality (2H, s), 7,49 (1H, m), 7,82 (2H, Shir. C)to 7.93 (1H, d), 8,21 (1H, s), of 9.30 (1H, s)/td> 483,22
I-7387,40 was 7.45 (1H, t), 7 ,50-7,70 (3H, m), a 7.85-8,00 (6H, m)and 8.1 (1H, d), 10,95 (1H, s)337
I-739to 2.85 (2H, t), of 3.33 (2H, m), of 6.52 (1H, t), 7,34 (6H, m), 7,46 (1H, t), 7,66 (2H, s), 7,82 (1H, d), 8,01 (1H, d), charged 8.52 (1H, s)337,3
I-740to 2.74 (2H, m), 3,24 (2H, m),6,46 (1H, m), 6,70 (2H, d), 7,05 (2H, d), 7,33 (1H, t), 7,46 (1H, t), the 7.65 (2H, s), 7,82 (1H, d), 8,01(1H, d), 9,17 (1H,s)353,3
I-741to 2.94 (2H, m)to 3.38 (2H, m), 6,55 (1H, m), 7,32 (3H, m), 7,49 (3H, m), 7,71 (2H, s), to 7.77 (2H, d), of 7.82 (1H, d), 8,01 (1H, d)416,3
I-742are 3.90 (2H, s), 7,24 (1H, m), 7,39 (3H, m), 7,56 (2H, m), 7,63 (1H, d), to 7.77 (2H, m), 7,86 (4H, m), 8,08 (1H, t), 9,58 (1H, s)397,4
I-743of 1.10 (3H, t), of 2.28 (2H, square), 7,34 (1H, t), 7,49 (5H, m), 7,80 (2H, s), 7,87 (1H, d), of 8.06 (1H, d), was 9.33 (1H, s)to 9.70 (1H, s)380,3
I-7443,62 (3H, s), 3,81 (6N, (C), 7,05 (2H, s), 7,82 (1H, DD), 7,89 (2H, Shir. C)8,01 (1H, d), 8,58 (1H, s), 9,38 (1H, s)467,22
I-7477,06 (1H, d), of 7.23 (1H, t), 7,35 (1H, t), 7,51 (2H, m), 7,86 (1H, d), to $ 7.91 (2H, s), 7,92 (1H, m), 8,10 (1H, d), RS 9.69 (1H, s)387,2
I-7484,19 (4H, m), 6,76 (1H, d), to 6.95 (1H, DD), 7,30 (1H, d), 7,37 (1H, t), 7,49 (1H, t), 7,78 (2H, s), 7,86 (1H, d), 8,07 (1H, d), 9,20 (1H, s)367,3
I-749to 2.29 (3H, s)of 6.71 (1H, d), 7,17 (1H, t), 7,29 (1H, t), 7,39 (1H, s), 7,42 (1H, d), of 7.48 (1H, t), 7,81 (2H, s), 7,87 (1H, d), of 8.06 (1H, d), a 9.35 (1H, s)
I-750then 7.20 (1H, m), 7,37-7,40 (1H, t), 7,50-of 7.55 (1H, t), of 7.90-of 8.00 (4H, m)and 8.1 (2H, m)343
I-7516,69 (2H, d), 7,33-7,41 (3H, m), 7,49 (1H, t), 7,76 (2H, Sirs), to 7.84 (1H, d), of 8.04 (1H, d), 9,06 (1H, s)325
I-752to 7.32 (1H, t), 7,40 (2H, Shir. C), 7,78 (2H, Shir. C)of 7.82 (1H, d), 8,03 (1H, d), of 8.06 (1H, s), 9,34 (1H, s), 12,84 (1H, Shir. C)349
I-7537,17 (2H, s), 7,40 (1H, t), 7,52 (1H, t), 7,69-7,74 (4H, m), 7,88 (1H, d), to $ 7.91 (2H, Shir. C)8,07 (1H, d), for 9.95 (1H, s)388
I-754of 2.97 (6H, s), of 7.36-7,38 (3H, m), 7,47-7,53 (1H, m), a 7.62 (2H, d), 8,07 (1H, d), 9,71 (1H, s)380
I-7553,17 (3H, d), of 7.36 (1H, t), 7,51 (1H, t), a 7.62 (2H, d), to 7.77 (2H, d), 7,87-7,89 (3H, m), 8,07 (1H, d), by 8.22 (1H, m), made up 9.77 (1H, s)366
I-756of 1.36 (3H, d), 4,67-4,69 (1H, m)to 5.13 (1H, d), 6.87 in (1H, d), 7,19 (1H, t), of 7.36 (1H, t), of 7.48-7,52 (2H, m), 7,58 (1H, s), 7,81(2H, Shir. C)7,86 (1H, d), 8,07 (1H, d), 9,37 (1H, s)353
I-757to 7.15 (1H, t), 7,34-7,39 (2H, m)to 7.50 (1H, t), 7,72-7,73 (1H, m), 7,81(2H, Shir. C)a 7.85-7,87 (2H, m), of 8.06 (1H, d), a 9.25 (1H, d)353
I-7583,62 (3H, s), 3,81(6N, C),? 7.04 baby mortality (2H, s), 7,37 (1H, m), 7,60 (1H, m), to 7.84 (2H, s), 8,07 (1H, m),9,40 (1H,s)433,33
I-7597,31(2H, s), 7,33 (1H, t), 7,35 (1H, t), of 7.48 (1H, t), 7,49 (1H, t), 7,80 (1H, d.o.d.), 7,87 (1H, d), 7,89 (2H, s), 8,07 (1H,d)of 8.09 (1H, s), 9,80 (1H, s)388,3
I-760224 (3H, C)to 7.09 (2H, d), 7,37 (1H, t), 7,49 (3H, m), 7,80 (2H, s), 7,86 (1H, d), 8,07 (1H, d), of 9.30 (1H, s)323,3
I-7616,93 (1H, d), 7,29 (1H, t), 7,39 (1H, t), 7,47 (1H, d), 7,53 (1H, t), 7,78 (1H, t), 7,86 (1H, d), 7,88 (2H, s), 8,10 (1H, d), 9,71 (1H, s)343,2
I-7624,34 (2H, d, J=6.4 Hz), 6,93-6,98 (1H, m), 7,20-7,24 (1H, m), 7,29-7,49 (6H, m), the 7.65 (2H, Shir. C)7,79-of 7.82 (1H, m), 7,98-8,03 (1H, m)323,26
I-763to 2.18 (3H, s), of 2.21 (3H, s), 7,02 (1H, d, J=7.8 Hz), 7,32-7,39 (3H, m), 7,47-7,53 (1H, m), 7,78 (2H, Shir. C), 7,87 (1H, d, J=8.0 Hz), 8,07 (1H, d,J = 7.8 Hz), 9,17 (1H, s)337,24
I-7643,66 (3H, s), a-3.84 (6H, s)to 4.01 (3H, s), 6,17 (2H, s), 6,99 (2H, s), 7,12 (1H, d), 7,33 (1H, t), a 7.62 (1H, d), 10,42 (1H, s)429,39
I-7653,62 (3H, s), 3,81(6H, s), of 3.97 (3H, s),? 7.04 baby mortality (2H, Shir. C), 7,10 (1H, d), 7,32 (1H, t), a 7.62 (1H, DD), 7,74 (2H, Shir. s), 9.28 are (1H, s)429,34
I-766of 1.37 (9H, s)to 3.64 (3H, s), 3,81 (6H, s), 6,00 (2H, Shir. C)6,94 (2H, s), of 6.99 (1H, s), 10,23 (1H, s)405,39
I-7673,62 (3H, s), of 3.80 (6H, s), 5,28 (2H, s), of 6.75 (1H, DD), 7,02 (2H, s), 7,07 (1H, d), 7,51 (1H, d), to 7.59 (2H, s), 9,16 (1H, s)414,31
I-7681,52-to 1.63 (4H, m), 3,03-is 3.08 (2H, m), 3,43-3,47 (2H, m), 3,62 (3H, s), of 3.80 (6H, s), and 4.40 (1H, t), of 5.82 (1H, t), is 6.78 (1H, DD), 7,03 (2H, s), 7,07 (1H, d), 7,54 (1H, d), to 7.59 (2H, s), 9,17 (1H, s)486,37
I-7697,34-7,41 (1H, m), 7,44-of 7.55 (3H, m), a 7.85-a 7.92 (3H, m), 7,98 (1H, d, J=2.4 Hz), 8,10 (1H, d, J=7.8 Hz), 9,81 (1H, s)37,20
I-770of 2.0 (2H, m)of 2.75 and 2.9 (4H, m)and 7.1 (1H, d), and 7.4 (2H, m), and 7.5 (2H, m), of 7.75 (2H, Sirs), a 7.85 (1H, d), with 8.05 (1H, d), and 9.2 (1H, s)349
I-771of 7.36 (1H, m), 7,44 (1H, m), and 7.5 (1H, m), 7,74 (1H, m), 7,84-7,9 (3H, m), 8,02 (1H, d), 8,07 (1H, d), 9,74 (1H, s)387
I-772with 3.79 (3H, s), 7,07-7,14 (1H, m), 7,21-7,29 (1H, m), 7,32-7,49 (1H, m), of 7.48-7,53 (1H, m), 7,56-to 7.64 (1H, m), 7,81(2H, Shir. C), 7,83-7,89 (1H, m), 8,03-of 8.09 (1H, m), 9,40 (1H, s)357,27
I-77334,39 (2H, d, J=6.2 Hz),? 7.04 baby mortality-7,10 (1H, m), 7,29-to 7.35 (1H, m), 7,40-7,51 (3H, m), 7,58-to 7.61 (1H, m), 7,69 (2H, Shir. C)7,79-of 7.82 (1H, m), 7,98-8,08 (1H, m)391,25
I-774of 2.72 (3H, s), 3,66 (3H, s), 3,83 (6N, C)6,14 (2H, Sirs), 7,06 (2H, s), 7,28 (1H, t), 7,37 (1H, m), 7,88 (1H, d), 10,36 (1H, s)413,35
I-7752,63 (3H, s), 3,62 (3H, s), 3,82 (6H, s), 7,05 (2H, s), 7,27 (2H, m), of 7.75 (2H, Sirs), 7,87 (1H, d), a 9.25 (1H, s)413,36
I-776a 3.83 (3H, s), to 6.19 (2H, Sirs), 7,18-7,28 (1H, m), 7,35-7,41 (1H, m), 7,45-7,58 (2H, m), 7,83-7,94 (1H, m), 7,98-of 8.09 (2H, m), 10,15 (1H, s)357,28
I-777the 3.65 (3H, s), 3,82 (6H, s), equal to 6.05 (2H, W), for 7.12 (2H, s), 7,37-7,39 (1H, m), 7,45-7,49 (2H, m), 7,66-to 7.68 (2H, m), of 8.06 (1H, s), 9,77 (1H, Shir.)425,38
I-7787,33 (2H, d), 7,37 (1H, t), to 7.50 (1H, t), a 7.62 (2H, d), 7,83 (2H, s), 7,88 (1H, d), 8,07 (1H, d), 9,58 (1H, s)343,2
I-779of 2.93 (6H, d), 6,27 (1H, DD), 6,83 (1H, d), 7,07 (1H, t), 7,26 (1H, m), 7,35 (1H, t), of 7.48 (1H, t), 7,63 (2H, s, 7,87 (1H, d), 8,07 (1H, d), to 9.15 (1H, s)352,4
I-780of 2.50 (3H, s), is 6.78 (1H, d), 7,27 (1H, t), 7,29 (1H m), of 7.36 (1H, t), 7,49 (1H, t), of 7.69 (1H, s), 7,81 (2H, s), 7,88 (1H, d), 8,08 (1H, d), to 9.45 (1H, s)355,3
I-781of 2.44 (3H, s), from 7.24 (2H, d), 7,38 (1H, t), to 7.50 (1H, t), 7,56 (2H, d), 7,80 (2H, s), 7,87 (1H, d), 8,07 (1H, d), 9,43 (1H, d)355,3
I-782for 1.49 (9H, s)6,91 (1H, d), 7,13 (1H, t), 7,38 (2H, m)to 7.50 (1H, t), of 7.70 (1H, s), to 7.77 (2H, s), 7,87 (1H, d), 8,03 (1H, d), which 9.22 (1H, s), 9,29 (1H, s)424,4
I-783of 3.57 (3H, s), the 3.65 (6H, s), make 6.90 (2H, s), 7,49 (2H, t), a 7.62 (2H, t), 7,78 (2H, s)to 8.14 (2H, d), with 9.14 (1H, s)370,4
I-7843,23-3,48 (7H, m)4,00 (3H, s), 7,08-7,11(1H, m), 7,35-7,41(1H, m), 7,49-of 7.55 (1H, m), 7.68 per-7,71(1H, m), 7,79-to $ 7.91 (4H, m), 8,05-to 8.12 (2H, m), 9,80 (1H, s)440,33
I-7853,62 (3H, s), 3,81 (6H, s),? 7.04 baby mortality (2H, s), 7,25 (1H, TD), to 7.68 (1H, DD), 7,80 (2H, Sirs), of 8.09 (1H, DD), of 9.30 (1H, s)417,29
I-786to 1.98 (3H, s), of 2.15 (3H, s), 7,15 (H, d), and 7.3 (2H, m), 7,4 (H, s), 7,5 (H, t), of 7.75 (2H, s), 7,9 (H, d), with 8.05 (H, d), or 9.1 (H, C)9,3 (H, C)380
I-787of 7.3 (2H, m), and 7.5 (1H, t), a 7.85 (3H, m), with 8.05 (3H, m), and 8.8 (1H,s) and 9,65 (1H, s)310
I-7884,89 (2H, s), 6,14 (1H, d), 6,76 (1H, s), to 6.88 (2H, m), 7,35 (1H, t), 7,49 (1H, t), 7,74 (2H, s), 7,86 (1H, d), with 8.05 (1H, d), 9,03 (1H, s)324,3
I-7891,70 of-1.83 (2H, m), or 3.28 (3H, s), 3,30 is-3.45 (4H, m)4,00 (3H, s), 7,06-7,10 (1H, m), 7,34-7,41 (1, m), 7,49-of 7.55 (1H, m), 7.68 per-7,71 (1H, m), 7,76-to $ 7.91 (4H, m), 8,05-to 8.12 (2H, m), 9,79 (1H, s)454,31
I-790to 4.15 (3H, s), 7,10 (2N, W), 7,25-to 7.32 (2H, m), 7,60-7,74 (8H, m), 9,73 (1H, Shir.)385,34
I-7914,19 (3H, s), 7,24 (2H, W), 7,26-7,34 (3H, m), 742-7,46 (1H, m), 7,58-to 7.64 (3H, m), of 7.70 (2H, m), 8,39 (1H, W), 9,63 (1H, Shir.)385,32
I-792of 3.95 (3H, s), 4,20 (3H, s), 7,25-7,30 (1H, d), 7,38 was 7.45 (2H, m), 7,50-of 7.55 (1H, t), 7,70 to 7.75 (1H, d), a 7.85-of 7.95 (3H, m), of 8.25 (1H, s), of 9.75 (1H,s)
I-793is 4.85 (3H, s), 7,12-to 7.18 (1H, d), 7,20-7,30 (2H, s), 7,45-of 7.55 (1H, t), of 7.70 (1H, s), 7,75-of 7.90 (3H, m), 8,12 ppm (1H, s), 8,3-8,5 (1H, s) , of 9.75 (1H, s)
I-794(CD3OD/CDCl3): at 2.93 (3H, d), 7,21 (2H, d), of 7.23 (2H, d), 7,44 (1H, t), to 7.50 (1H, t), 7,52 (2H, d), 7,81 (2H, m)403,4
I-7953,62 (2H, s)to 3.64 (3H, s), 6,79 (1H, d), of 7.23 (1H, t), 7,38 (1H, t), of 7.48 (1H, s), 7,52 (1H, t), 7,56 (1H, d), 7,80 (2H, s), 7,88 (1H, d), 8,08 (1H, d), 9,40 (1H, s)381,3
I-796of 3.85 (3H, s), 7,00 (1H, DD), 7,28 (2H, Sirs), 7,35 (1H, d), 7,46-7,49 (2H, m), 7,81 (1H, d), 7,82 (2H, Sirs), to 7.93 (1H, d), of 8.09 (1H, s), 9,36 (1H, s)418,23
I-797of 1.40 (9H, s), 1,54-of 1.66 (2H, m), 2,94 totaling 3.04(2H, m), 3,24-to 3.35 (2H, m)to 4.01(3H, s), PC 6.82 (1H, shirt, J=5.5 Hz), 7,05 to 7.62 (1H, m), 7,34-7,41 (1H, m), of 7.48-of 7.55 (1H, m), 7.68 per-of 7.70 (1H, m), to 7.77-7,81 (1H, m), 7,81-to $ 7.91 (3H, m), 8,05-8,10 (1H, m), 9,80 (1H, s)539,41
I-7982,38-2,52 (6H, m), 3,38-of 3.48 (2H, m), to 3.58-3,68 (4H, m), Android 4.04 (3H, s), 7,08-7,12 (1 is, m), 7,35-7,41 (1H, m), 7,49-7,56 (1H, m), 7,70-7,74 (1H, m), 7,80-a 7.92 (4H, m), 8,04-8,10 (1H, m), 8,23-8,29 (1H, m), 9,80 (1H, s)495,39
I-8001,62-of 1.74 (2H, m), 2,29-to 2.41 (6H, m), of 3.25 to 3.36 (2H, m), 3,52-3,61 (4H, m)4,00 (3H, s), 7,05-to 7.61 (1H, m), 7,34-7,41(1H, m),of 7.48-of 7.55 (1H, m), 7.68 per-7,71(1H, m), 7,73-7,80 (1H, m), 7,81-of 7.90 (3H, m), 8,00-8,10 (2H, m), 9,78 (1H, s)509,37
I-801of 2.81(3H, d, J=at 5.3 Hz)to 3.99 (3H, s),? 7.04 baby mortality-7,10 (1H, m), 7,34-7,40 (1H, m), 7,69-7,71 (1H, m), 7,78-to $ 7.91 (1H, m), 7,82-to $ 7.91 (3H, m), 7,95-8,00 (1H, m), 8,06-8,10 (1H, m), 9,78 (1H, s)396,31
I-802of 3.85 (3H, s), 7,12-to 7.18 (3H, m), 7,70-a 7.85 (8H, m), of 9.75 (1H, s)
I-8036,45-6,50 (2H, s), 6,95-7,0 (1H, d), 7,30 (1H, s), 7,33-7,37 (1H, d), and 7.4 (1H, s), 7,45 is 7.50 (1H, t), 7,65-of 7.70 (1H, d), 7,70 to 7.75 (1H, s), 7,78-7,83 (1H, d), 8,07 (1H, s), 9,75 (2H, m)
I-8047,40 was 7.45 (1H, t), 7,50-of 7.55 (1H, t), of 7.90-of 7.95 (3H, m), 8,05-8,15 (5H, m)
I-8056,60 (1H, d), 6,98-7,05 (1H, d), 7,25-7,30 (2H, s), 7,40 ppm (1H, s), and 7.5 (1H, d), 7,80-of 7.90 (3H, m), 7,95-of 8.00 (2H, d), 9,8-to 9.9 (1H,s), 10,45 (1H, s)404
I-8062,32 (3H, s), a 2.36 (3H, s), 3,61 (3H, s), of 3.77 (6H, s)to 4.16 (3H, s), 6,97 (2H, s), of 7.36 (2H, d), a 7.62 (2H, Sirs), 9,05 (1H, Sirs)363,34
I-807is 2.40 (3H, d), 3,61 (3H, s), of 3.78 (6H, s), 7,00 (2H, s), 7,27 (1H, d), 7,42 (2H, Shir. C), 9,11 (1H, s)363,34
I-808? 7.04 baby mortality-to 7.15 (1H, m), 7,34-7,41 (1H, m), 7,49-of 7.55 (1H, m), to 7.59-to 7.67 (2H, m), 7,70-7,92 (6H, m), 8,04-8,11 (1H, m), 9,74 (1H, is) to 352.27
I-8096,24 (2H, s), 7,16-7,29 (1H, m), 7,31-7,42 (1H, m), 7,49-to 7.59 (1H, m), 7,80-to 7.99 (4H, m), 8,00-8,10 (2H, m)10,416 (1H, s)352,23
I-810of 7.25 (1H, m), 7,30-7,40 (3H, m), 7,45-of 7.55 (1H, m), 7,75-to $ 7.91 (4H, m), 7,99-8,02 (1H, m), 8,04-8,10 (1H, m), of 9.51 (1H ,s)352,23
I-8110,81 (3H, t), 1,19-of 1.45 (4H, m), 2,79-2,89 (2H, m), 7,25-7,31 (1H, m), 7,34-7,40 (1H, m), 7,41-of 7.55 (3H, m), 7,76-to $ 7.91 (4H, m), 8,05-of 8.15 (2H, m), 9,79 (1H, s)444,27
I-8127,05-to 7.18 (6H, m), 7,20-of 7.23 (1H, t), 7,40-to 7.50 (4H, m), 7,70 to 7.75 (2H, d), 7,80-a 7.85 (2H, d), 8,45-of 8.50 (2H, s), 9,80-9,85 (1H,s), or 10.9 (1H, s)482
I-8137,05-7,20 (8H, m), 7,35 is 7.50 (4H, m), 7,70 to 7.75 (2H, d), 7,80-a 7.85 (2H, d), 9,80-9,95 (1H, s)480
I-8147,14 (2H, Sirs), 7,27 (1H, TD), 7,69-7,74 (5H, m), of 7.90 (2H, Sirs), 8,11(1H, DD), 9,92 (1H, s)406,22
I-8153,51 (2H,C)6,79 (1H, d), 7,21(1H, t), of 7.36 (1H, t), 7,47 (1H, s)to 7.50 (2H, m), 7,80 (2H, s), 7,87 (1H, d), 8,07 (1H, d), 9,38 (1H, s), 12,27 (1H, s)367,3
I-816of 3.48 (2H,C)then 7.20 (2H, d), 7,34 (1H, t), 7,38 (1H, t), of 7.48 (1H, t), to 7.50 (2H, d), 7,79 (2H, s), 7,87 (1H, d), of 8.06 (1H, d), a 9.35 (1H, s), 12,18 (1H, s)367,3
I-817to 2.42 (3H, s), 7,25 (2H, s), 7,29 (2H, m), 7,42 (1H, t), 7,49 (2H, Sirs), to 7.77 (1H, DD), of 8.06 (1H, s),9,62 (1H, s)352,24
I-818a 1.5-1.6 (2H, m), about 2.2-2.3 (6H, m), 2,8-2,9 (2H, m), 3,45-3,5 (4H, m), 6,2 (2H, s), 7,35 to 7.7 (5H, m), with 8.0 and 8.1(3H, m), of 8.25 (1H, s) and 10.4(1H, C)515
I-8192,91-3,10 (4H, m), 3,61-3,71(4H, m), 7,20-7,28 (1H, m), 7,35-7,41(1H, m), 7,49-to 7.59 (2H, m), 7,75-of 7.60 (1H, m), a 7.85-to 7.93 (3H, m), 8,08-8,10 (1H, m), 8,19-8,21(1H, m), of 9.89 (1H, s)458,24
I-8203,3 (6H, s), and 7.4 (1H, m), 7,55 (1H, m), and 7.6 to 7.7 (2H, m), 7,78-7,8 (2H, m), 7,88 to 7.9 (3H, m)and 8.1 (1H, m) and 10.5 (1H, s)416
I-8211,3-1,4 (2H, m), 1,5-1,6 (4H, m), 2,8-2,9 (4H, m), and 7.4 (1H, m), 7,5 (H, m), 7,6-the 7.65 (2H, m), 7,78-7,8 (2H, m), 7,9-of 7.95 (3H, m)and 8.1 (1H, d), of 10.05 (H, C)456
I-8222,22-of 2.38 (6H, m), 2,90-of 3.00 (2H, m), 3,42-3,53 4H, m), 6,21(2H, Sirs), 7,35-7,42 (1H, m), 7,49-to 7.68 (4H, m), 7,98-to 8.12 (3H, m), 8,29 (1H, Sirs), the 10.40 (1H, Sirs)501,28
I-8232,24-of 2.38 (6H, m), 2.91 in is 3.00 (2H, m), 3.43 points-of 3.50 (4H, m), 7,28-7,56 (5H, m), 7,75-7,81 (4H, m), 8,04-8,10 (1H, m), 8,11-8,18 (1H, m), 9,79 (1H, s)501,29
I-824to 1.61 (6H, d), 5,59 (1H, m), 7,16 (2H, Sirs), 7,28 (5H, m), 7,42 (1H, t), 7,66 (2H, m), 7,81 (1H, m), 8,14 (1H, t), 9,54 (1H, s)413,39
I-8253,63 (3H, s), with 3.79 (6H, s), of 5.83 (2H, s), 7,13 (3H, m), of 7.36 (2H, t), to 7.68 (2H, d), to 9.57 (1H, s)9,68 (1H, s)385,4
I-826of 3.60 (3H, s), of 3.80 (6H, s), 7,00 (2H, s), to 7.15 (1H, t), 7,37 (4H, m), 7,63 (2H, d), 9,01 (1H, s), 9,40 (1H, s)385,4
I-827the 2.8 and 2.9 (4H, m), up 3.6-3.7 (4H, m), 7,4 (H, m), 7,5 (H, m), and 7.6 to 7.7 (2H, m), 7,75-7,8 (2H, m), 7,9-of 7.95 (2H, m, NH), 8,1 (H, m) and 10.1 (H, C)458
I-8282,40-to 2.55 (3H, d), 7,25-7,30 (1H, m), 7,30-7,41 (2H, m, of 7.48-of 7.55 (2H, m), 7,78-to $ 7.91 (4H, m), 8,06-of 8.15 (2H, m), 9,79 (1H, s)402,24
I-8297,13 (2H, s), 7,35-7,39 (3H, m), 7,45-of 7.48 (1H, m), the 7.65 (2H, W), 7,68-7,74 (6H, m), 8,03 (1H, W),9,84 (1H, Shir.)414
I-8301,20-of 1.46 (6H, m), 2,15-2,39 (6iH, m), 2,90-of 3.00 (2H, m), 7,26-of 7.55 (5H, m), 7,76-to 7.93 (4H, m), 8,05-8,18 (2H, m), 9,80 (1H, s)499,33
I-8312,4 (3H, d),7,15 (H, m), 7,4 (H, m), 7,5 (H, m), and 7.7 (2H, m), of 7.75 (2H, m), 7,9 (3H, m), 8,05 (H, m) and 9,95 (H, C)402
I-832and 2.14 (3H, s), 2,23-to 2.42 (4H, m), 2,92-to 3.02 (4H, m), 6,21 (2H, s), 7,34-of 7.48 (2H, m), 7,50-7,58 (1H, m), 7,65-7,71 (1H, m), 8,00-8,10 (3H, m), 8,28-8,31 (1H, m), the 10.40 (1H, s)471,27
I-833and 2.14 (3H, s), 2,33 is 2.43 (4H, m), 2,93-3,03 (4H, m), 7,20-7,26 (1H, m), 7,34-7,41 (1H, m), 7,49-7,58 (2H, m), 7,71-7,79 (1H, m), 7,81-to $ 7.91 (3H, m), 8,09-to 8.12 (1H, m), 8,19-8,24 (1H, m), 9,86 (1H,s)471,31
I-834of 2.08 (6H, s), 2,25 of-2.32 (2H, m), 2,88 are 2.98 (2H, m), 7,28-7,58 (5H, m), 7,78-a 7.92 (4H, m), 8,02-8,16 (2H, m), 9,79 (1H, s)459,37
I-8357,44 (2H, Sirs), 7,65-of 7.69 (4H, m), 7,74-7,88 (3H, m), with 8.05 (1H, d), at 8.36 (1H, DS), which 9.22 (1H, d)382,29
I-836the 3.65-and 3.72 (2H, m), 3.95 to 4.00 points (2H, t), 4.80 to around 4.85 (1H, t), 6,85-to 6.95 (4H, m), 7,55-of 7.70 (4H, DD), and 9.0 (1H, s)448
I-837of 1.37 (3H, t), of 4.66 (2H, square), 5,9 1(2H, s), 7,30 (2H, m), 7,39 (2H, Shir. C), 7,47 (1H, d), at 7.55 (1H, t), of 7.69 (2H, m), 8,02 (1H, d), 8,08 (1H, s), is 10.75 (1H, s)399,29
I-8387,21(2H, s), 7,47 (2H Sirs), 7,73 to 7.75 (2H, m), 7,83-a 7.85 (2H, m), 8,02-of 8.06 (2H, m), 10,07 (1H, Sirs), 12,96 (1H, Sirs)432,20
I-8393,13-of 3.54 (4H, m), 5,02 (2H, s), 6,21-6,40 (1H, m), 7,00-to 7.18 (2H, m), 7,20 is 7.50 (6H, m), 7,60-8,23 (5H, m), 9,50-a 9.60 (1H, m)525,3
I-840of 2.86 (3H, Sirs), 6,60-6,70 (1H, m), to 7.15 (2H, Sirs), 7,56-7,93 (7H, m), 8,28-to 8.40 (1H, m), RS 9.69 (1H, s)362,32
I-841is 1.81 (4H, m), 2,67-of 2.72 (4H, m), 7,14 (2H, s), 7,52 (2H, W), 7,63-of 7.70 (4H, m), 9,81 (1H, s)392,2
I-8427,14-7,16 (3H, m), 7,45-7,49 (6H, m), to 7.67-7,73 (4H, m)9,68 (1H, s), 11,36 (1H, Shir.)430,3
I-843to 6.57 (2H, s), 7,32 (2H, m), 7,82-7,88 (4H, m), 9,54 (1H, Shir.)373,2
I-844of 3.4 to 3.7 (10H, m), 4.4 to 4.5 (2H, s), 7,1-7,2 (4H, m), between 7.4 to 7.5 (1H, d), 7,70 to 7.75 (2H, d), 7,80-a 7.85 (2H, d), 9,45-of 9.55 ( 2H, s), and 10.0 (1H, s)516
I-845the 2.8 (3H, s), of 3.0-3.4 (10H, m), 4,2-4,3 (2H, s), 7,1-7,2 (2H, d), 7,2-of 7.25 (1H, d), 7,4 was 7.45 (2H, d), 7,70 to 7.75 (2H, d), 7,80-a 7.85 (2H, d), and 10.0 (1H, s)530
I-846however, 4.40 (2H, s), 7,05-7,10 (2H, d), to 7.15 (2H,C)7,35-7,45 (2H, m), 7,55 (1H, s), 7,70 to 7.75 (2H, d), a 7.85-of 7.90 (2H, d), and 10.0 (1H,s)461
I-8477,13 (2H, Shir. C), 7,74 (4H, m), 7,83 (2H, s), of 8.06 (1H, d), 8,17 (1H, d), 9,78 (1H, s)367,2
I-8483,15-3,19 (2H, m), 3,41-3,47 (2H, m), 7,00-7,03 (2H, m), 7,10 (2H, s), 7,63-to 7.68 (2H, m), 7,76-7,79 (4H, m), 8,30 (1H, Sirs), 9,43 (1H, s)502,32
I-853 to 7.15 (2H, s), 7,54-7,58 (1H, m), 7,72-7,80 (5H, m), 7,99-of 8.04 (2H, m), 8,10-to 8.12 (3H, m)8,64 (1H, d), to 9.70 (1H, s)382,32
I-8547,16 (2H, s), 7,72 (2H, d), 7,79 (2H, d), of 8.00 (1H, d), 8,29 (2H, Sirs), of 8.37 (1H, d), 8,86 (1H, s), 9,88 (1H, s)389,24
I-8552,80 (3H, d), 7,10 (2H, s), 7,42 (2H, Sirs), 7.68 per-7,74 (2H, m), 7,83-a 7.85 (2H, m), 7,92-7,94 (2H, m), to 8.45 (1H, Sirs), 10,00 (1H, Sirs), 11,99 (1H, Sirs)445,32
I-852of 2.25 ppm (3H, s), of 3.95 ppm (3H, s), 7,6-7,8 ppm (4H, m), 7,8-7,9 ppm (2H, s), of 7.90-of 7.95 ppm (2H, d), 10,0 ppm (1H,s)436
I-851the 1.44 (3H, t), 4,78 (2H, square), 7,29 (5H, m), 7,45 (1H, t), a 7.62 (3H, m), 7,79 (1H, Sirs), 8,19 (1H, m), 9,67 (1H, s)
I-849of 5.75 (2H, s), 7,21(5H, m), 7,25 (1H, t), was 7.45 (1H, s), 7,53 (1H, d), a 7.62 (2H, d), of 8.00 (1H, s), 8,32 (1H, d)371,4
I-8506,01 (2H, s), 7,20 (2H, m), 7,28 (2H, s), 7,44 (1H, Shir. C)to 7.64 (1H, Shir. C)7,76 (2H, d), to 7.93 (2H, d), 10,98 (1H, s), is 12.85 (1H, s)371,4
I-856or 4.31 (2H, s), was 7.08 (2H, s), 7,20 (2H, m), 7,30 (5H, m), 7,72 (4H, m), 7,79 (1H, d), 8,02 (1H, d), 9,78 (1H, s)423,4
I-8573,07-3,18 (2H, m), 3,49-3,51 (2H, m), 6,36-to 6.43 (1H, m), 7,10-7,17 (2H, m), 7,60-8,21 (8H, m), 9,62 (1H, Sirs),391,3
I-858of 2.45 (3H, d), 7,16 (2H, s), 7,80 (2H, s), 7,86 (2H, d), 8,20-8,21 (3H, m), 8,93 (1H, s), to 9.93 (1H, s)403,23
I-8597,14 (2H, s), 7,58 (3H, d), 7,74 (4H, m), 7,94 (2H, s), 8,16 (3H, m), to 8.45 (1H, d),9,78 (1H, C)409,3
I-8643,33-3,61 (4H, m), 4,76-a 4.86 (1H, m), 6,70-6,76 (1H, m), 7,10-7,20 (2H, m), 7,65-7,87 (7H, m), 8,28-8,35 (1H, m), RS 9.69 (1H, s)392,28
I-860of 2.86 (3H, s), 2,87 (3H, s), 3,37-to 3.41(2H, m), 3,80-of 3.85 (2H, m), 7,16 (2H,C)7,49 (2H, s), 7,58-of 7.60 (2H, m), to 7.67 (1H, t, J=5.8 Hz), 7,72-7,74 (2H, m), 9,36 (1H, W), 9,76 (1H, Shir.)425,3
I-861of 2.81 (3H, s), 3,12-of 3.25 (4H, m), 3,48-3,51 (2H, m), 3,86-are 3.90 (2H, m), 7,00 (2H, s), 7,13 (2H, s), 7,62-to 7.64 (2H, m), 7,71 to 7.75 (2H, m), 9,65 (1H, s), 9,78 (1H, Shir.)437,3
I-8623,05 (3H, d, J=5.0 Hz), 7, 14 (2H, s), 7,49 (2H, s), EUR 7.57-to 7.59 (2H, m), 7,71-7,74 (2H, m), 9,74 (1H, Shir.)368,3
I-8637,11(2H, s), 7.23 percent (2H, s), 7,69 (4H, m)to 9.70 (1H, Shir.)373,2
I-8653,17-3,20 (2H, m), 3,84-are 3.90 (2H, m), 6,85-6,91 (4H, m), of 7.64-to 7.67 (2H, m), 7,74-7,76 (2H, m), 9,31 (1H, s)447,29
I-866of 1.95 (1H, m), 2,2 (1H, m), 3,1(1H, m)of 3.25 (1H, m)to 3.35 (1H, m), of 3.45 (1H, m), 4,6 (1H, Sirs), 6,7 (1H, Sirs, ar), 7,2 (2H, Sirs), 7,7-of 7.95 (4H, m)and 8.1 (1H, Sirs), and 8.4 (1H, Sirs), and 8.4 (1H, s), and 9.2 (1H, Sirs) to 9.45 (1H, s)417
I-867for 1.49 (3H, sird, J=5,9 Hz), 5,20 to 5.35 (1H, m), 6,72-to 6.80 (1H, m), 7,10-7,80 (10H, m), 8,09-8,30 (2H, m)9,68 (1H, s)452,3
I-8681,86-of 2.20 (2H, m), 3,35-of 3.60 (2H, m), 4,58-4,80 (1H, m), 6,40, 6,80, 1H, Sirs X2), 7,16-7,58 (10H, m), 7.68 per-of 7.90 (4H, m), 8,12 is 8.38 (2H, m), 9,74 (1H, s)482,4
I-869of 2.64 (3H, s), 4,18 (2H, t), 95 (4H, C), 7,66 (2H, d), 7,76 (2H, d), 8,42 (2H, Sirs), 9,36 (1H, s)461,3
I-8700,9-1,9 (4H, m), 2,6-3,1 (4H, m), and 3.8 (1H, m, CH), 4,3 (2H, Sirs), 6,8 (1H, s), and 7.1 (2H, Sirs) 7,7-7,9 (6H, m), and 8.4 (1H, s), and 9.7 (1H, s)431
I-8714,39-and 4.68 (2H, m), 6,70-6,83 (1H, m), 7,10-of 7.48 (6N, m), 7,60-to 7.84 (5H, m), 8,09-8,39 (2H, m), RS 9.69 (1H, s)438
I-8722,69 (6N, Sirs), 4,22 (2H, t), of 6.96-7,05 (4H, m), 7,11 (2H, s), to 7.67 (2H, d), to 7.77 (2H, d), 9,46 (1H, s)475?3

C) Biological data:

Example 1: inhibition of FLT-3:

Screening of the compounds was performed on their ability to inhibit the activity of FLT-3 using analysis of binding to a radiometric filter. The analysis conducted control include33P in the substrate poly(Glu, Tyr) 4:1 (pE4Y). The reaction was performed in a solution containing 100 mm HEPES (pH 7.5), 10 mm MgCl2, 25 mm NaCl, 1 mm DTT, 0.01% of BSA and 2.5% DMSO. The final substrate concentration in the analysis were 90 μm ATP and 0.5 mg/ml raw (both from Sigma Chemicals, St Louis, MO). The final concentration of compounds are usually between 0.01 and 5 microns. Usually titration on 12 points spent preparing serial dilutions from 10 mm of the test compounds in the source DMSO. The reaction was carried out at room temperature.

Got two solutions for analysis. Solution 1 contains 100 mm HEPES (pH 7.5), 10 mm MgCl2, 25 mm NaCl, 1 mg/ml raw and 180 μm ATP (containing 0.3 µci [γ- 33P]ATP for each reaction). Solution 2 contains 100 mm HEPES (pH 7.5), 10 mm MgCl2, 25 mm NaCl, 2 mm DTT, 0.02% of BSA and 3 nm FLT-3. The analysis was carried out on 96-well tablet by mixing 50 ál of solution 1 with 2.5 ml of test compounds. The reaction was initiated by solution 2. After incubation for 20 minutes at room temperature the reaction was stopped by 50 μl of 20% TCA containing 0.4 mm ATP. All the volumes of the reactions are then carried in the device for filtration and washed with 5% TCA using Harvester 9600 from TOMTEC (Hamden, CT). Number include33R Reu were analyzed by scintillation counter, Packard TopCount Microplate (Meriden, CT). The data were selected using the software Prism, while receiving IC50or Ki.

In General, compounds of the invention, including compounds in table 1 are effective for the inhibition of FLT-3.

Example 2: inhibition of c-KIT

Screening of the compounds was performed on their ability to inhibit the activity of c-KIT using analysis of binding to a radiometric filter. The analysis conducted control include33P in the substrate poly(Glu, Tyr) 4:1 (pE4Y). The reaction was performed in a solution containing 100 mm HEPES (pH 7.5), 10 mm MgCl2, 25 mm NaCl, 1 mm DTT, 0.01% of BSA and 2.5% DMSO. The final substrate concentration in the analysis were 700 μm ATP and 0.5 mg/ml raw (both from Sigma Chemicals, St Louis, MO). The final concentration of compounds are usually is between 0.01 and 5 microns. Usually titration on 12 points spent preparing serial dilutions from 10 mm of the test compounds in the source DMSO. The reaction was carried out at room temperature.

Got two solutions for analysis. Solution 1 contains 100 mm HEPES (pH 7.5), 10 mm MgCl2, 25 mm NaCl, 1 mg/ml raw and 1.4 μm ATP (containing 0.5 µci [γ-33P]ATP for each reaction). Solution 2 contains 100 mm HEPES (pH 7.5), 10 mm MgCl2, 25 mm NaCl, 2 mm DTT, 0.02% of BSA and 25 nm c-KIT. The analysis was carried out on 96-well tablet by mixing 33 μl of solution 1 and 1,65 µl of the tested compounds. The reaction was initiated 33 μl of solution 2. After incubation for 20 minutes at room temperature the reaction was stopped by 50 μl of 10% TCA containing 0.2 mm ATP. All the volumes of the reactions are then carried in the device for filtration and washed with 5% TCA using Harvester 9600 from TOMTEC (Hamden, CT). Number include33R Reu were analyzed by scintillation counter, Packard TopCount Microplate (Meriden, CT). The data were selected using the software Prism, while receiving IC50or Ki.

In General, compounds of the invention, including compounds in table 1 are effective for the inhibition of c-KIT.

Example 3: Inhibition of GSK-3

Screening of the compounds was performed on their ability to inhibit the activity of GSK-3β (AA 1-420) using standard system associated enzyme (Fox et a. (1998) Protein Sci. 7, 2249). The reaction was performed in a solution containing 100 mm HEPES (pH 7.5), 10 mm MgCl2, 25 mm NaCl, 300 μm NADH, 1 mm DTT and 1.5% DMSO. The final substrate concentration in the analysis were 20 μm ATP (Sigma Chemicsls, St. Louis, MO) and 300 μm peptide (American Peptide, Sunnyvale, CA). The reaction was carried out at 30°and 20 nm GSK-3β. The final concentrations of the components of the system associated enzyme were 2.5 mm of phosphoenolpyruvate, 300 μm NADH, 30 μg/ml pyruvate kinase and 10 μg/ml lactate dehydrogenase.

Received source buffer solution for analysis, containing all of the reagents listed above, with the exception of the APR and interest of the test compounds. The original buffer solution for assay (175 μl) were incubated in 96-well-plate with 5 μl of interest of the test compounds at a final concentration ranges from 0.002 μm to 30 μm at 30°within 10 minutes Usually titration on 12 points spent preparing serial dilutions (from 10 mm initial solutions connection) DMSO tested compounds in the "child" tablets. The reaction was initiated by adding 20 μl of ATP (final concentration 20 μm). The reaction rate was obtained with the use of the apparatus for reading tablets Molecular Devices Spectramax (Sunnyvale, CA) for 10 min at 30°C. the Value of Kidetermined from the data speeds as a function of the concentration of the inhibitor.

In General, the connection is subramania, including compounds of table 1, are effective for the inhibition of GSK-3.

Example 4: inhibition of CDK-2

Screening of the compounds was performed on their ability to inhibit the activity of CDK-2/cyclina And using the standard system associated enzyme (Fox et al. (1998) Protein Sci. 7, 2249). Reactions were performed in 100 mm HEPES (pH 7.5), 10 mm MgCl2, 25 mm NaCl, 1 mm DTT and 1.5% DMSO. The final substrate concentration in the analysis were 100 μm ATP (Sigma chemicals) and 100 μm peptide (American Peptide, Sunnyvale, CA). The analysis was carried out at 30°and 25 nm CDK-2/cyclina A. Final concentration of the components of the system related enzymes were 2.5 mm of phosphoenolpyruvate, 350 μm NADH, 30 μg/ml pyruvate kinase and 10 μg/ml lactate dehydrogenase.

Received source buffer solution for analysis, containing all of the reagents listed above, with the exception of CDK-2/cyclina And, DTT and interest of the test compounds. 56 μl of the test reaction mixture was placed in a 384-well plate followed by addition of 1 μl of 2 mm source DMSO solution containing the test compound (final concentration 30 μm). The tablet is pre-incubated for ˜ 10 minutes at 30°and the reaction was initiated by adding 10 μl of enzyme (final concentration 25 nm). The reaction rate was obtained with the use of the apparatus for reading tablets BioRad Ultramark (Hercules, CA) which is the situation for 5 minutes at 30° C. the Value of Kiwas determined by standard methods.

In General, compounds of the invention, including compounds in table 1 are effective for the inhibition of CDK-2.

Example 5: inhibition of SRC

Compounds were evaluated as inhibitors of Src-kinase person using or based analysis of radioactivity, or spectrophotometric analysis.

Analysis of A inhibition of Src: analysis on the basis of radioactivity

Compounds were analyzed as inhibitors full-size recombinant Src kinase (Upstate Biotechnology, cat. No. 14-117), expressed and purified from baculovirus cells. Monitoring the activity of Src held after including33P from ATP to tyrosine random polymer of poly-Glu-Tyr composition, Glu:Tyr=4:1 (Sigma, cat. No. P-0275). Below are the final concentrations of the components of the analysis: 0.05 M HEPES, pH of 7.6, 10 mm MgCl2, 2 mm DTT, 0.25 mg/ml BSA, 10 μm ATP (1-3 µci33P-ATP per reaction), 5 mg/ml poly Glu-Tyr, and 1-2 units of recombinant Src kinase person. In a typical analysis of the components of the reaction except ATP, pre-mixed and aliquots were taken for analysis in wells. Dissolved in DMSO inhibitors were added to the wells to obtain a final concentration of DMSO of 2.5%. Analytical plates were incubated at 30°C for 10 min before initiating the reaction33 P-ATP. After a 20 minute reaction reaction extinguished 150 ál of 10% triperoxonane acid (TCA)containing 20 mm Na3RHO4. Extinguished the samples are then transferred in 69-well plate for filtration (Whatman, UNI-Filter GF/F Glass Fiber Filter, cat. No. 7700-3310)mounted on the vacuum system for a tablet for filtering. Tablets for filtration was washed four times with 10% TCA containing 20 mm Na3PO4and then 4 times with methanol. To each well was then added 200 μl of scintillation fluid. The plates were sealed and the amount of radioactivity associated with the filters was quantitatively determined on TopCount scintillation counter. Incorporated radioactivity was plotted on a graph as a function of the concentration of the inhibitor. Data were selected for the model kinetics of competitive inhibition, to obtain the Kifor the connection.

Analysis of inhibition of Src: spectrophotometric analysis

ADP produced from ATP catalyzed by recombinant Src kinase person phosphorylation of poly (Glu-Tyr substrate, quantitatively determined using analysis of the bound enzyme (Fox et al. (1998) Protein Sci 7, 2249). In this analysis, one molecule of NADH is oxidized to NAD, each molecule of ADP produced in the reaction kinase. The disappearance of NADH is usually observed at 340 nm.

The final concentration of the components of the analysis I have are the following: 0.025 M HEPES, pH of 7.6, 10 mm MgCl2, 2 mm DTT, 0.25 mg/ml poly Glu-Tyr, and 25 nm recombinant Src kinase person. The final concentrations of the components of the system associated enzyme are 2.5 mm phosphoenolpyruvate, 200 μm NADH, 30 μg/ml pyruvate kinase and 10 μg/ml lactate dehydrogenase.

In a typical analysis of all the components, except for ATF, pre-mixed and aliquots were added to the analytical tablet. aliquots were taken for analysis in wells. Dissolved in DMSO inhibitors were added to the wells to obtain a final concentration of DMSO of 2.5%. Analytical tablet incubated at 30°C for 10 min before initiating the reaction with 100 μm ATP. Monitoring changes in the absorption at 340 nm with time, the rate of the reaction was carried out on the reader tablet molecular way. The data rate as a function of the concentration of the inhibitor was picked up by the model of the kinetics of competitive inhibition to obtain Kifor the connection.

In General, compounds of the invention, including compounds in table 1 are effective for the inhibition of the SRC.

Example 6: inhibition of SYK

Screening of the compounds was performed on their ability to inhibit the activity of Syk using standard system associated enzyme (Fox et al. (1998) Protein Sci. 7, 2249). Reactions were performed in 100 mm HEPES, pH 7.5, 10 mm MgCl2, 25 mm NaCl, 1 mm DTT and 1.5% DMSO. The final concentration and the Alize were 200 μm ATP (Sigma Chemical, Co.) and 4 μm poly Gly-Tyr peptide (Sigma Chemical, Co.). The analysis was carried out at 30°and 200 nm Syk. The final concentrations of the components of the system associated enzyme were 2.5 mm of phosphoenolpyruvate, 300 μm NADH, 30 μg/ml pyruvate kinase and 10 μg/ml lactate dehydrogenase.

Received source buffer solution for analysis, containing all of the reagents listed above, with the exception of Syk, DTT and interest of the test compounds. 56 μl of the test reaction mixture was placed in a 96-well plate followed by addition of 1 μl of 2 mm source DMSO solution containing the test compound (final concentration 30 μm). The tablet is pre-incubated for ˜ 10 minutes at 30°and the reaction was initiated by adding 10 μl of enzyme (final concentration 25 nm). The reaction rate was obtained with the use of reader-tablet (Hercules, CA) for 5 minutes at 30°and the values of Kiwas determined by standard methods.

In General, compounds of the invention, including compounds in table 1 are effective for the inhibition of SYK.

Example 7: inhibition of FMS

Screening of the compounds was performed on their ability to inhibit the activity of FMS using analysis of binding radiometric filter. The analysis performs control including33P in the substrate poly(Glu, Tyr) 4:1 (pE4Y). Reactions were carried out in process is e, containing 100 mm HEPES (pH 7.5), 10 mm MgCl2, 25 mm NaCl, 1 mm DTT, 0.01% of BSA and 2.5% DMSO. The final substrate concentration in the analysis were 90 μm ATP and 0.5 mg/ml raw (both from Sigma Chemicals, St Louis, MO). The final concentration of compounds are usually between 0.01 and 5 microns. Usually titration on 12 points spent preparing serial dilutions from 10 mm of the test compounds in the source DMSO. The reaction was carried out at room temperature.

Got two solutions for analysis. Solution 1 contains 100 mm HEPES (pH 7.5), 10 mm MgCl2, 25 mm NaCl, 1 mg/ml raw and 180 μm ATP (containing 0.3 µci [γ-33P]ATP for each reaction). Solution 2 contains 100 mm HEPES (pH 7.5), 10 mm MgCl2, 25 mm NaCl, 2 mm DTT, 0.02% of BSA and 3 nm FMS. The analysis was carried out on 96-well tablet by mixing 50 µl of each solution of 1 and 2.5 ml of the tested compounds. The reaction was initiated by solution 2. After incubation for 20 minutes at room temperature the reaction was stopped by 50 μl of 20% TCA containing 0.4 mm ATP. All the volumes of the reactions are then carried in the device for filtration and washed with 5% TCA using Harvester 9600 from TOMTEC (Hamden, CT). Number include33R Reu were analyzed by scintillation counter, Packard TopCount Microplate (Meriden, CT). The data were selected using the software Prism, while receiving IC50or Ki.

In General, compounds of the invention, including compounds in table 1 are the Xia effective for inhibition of FMS.

Example 8: analysis of the inhibition of Rock

Screening of the compounds was performed on their ability to inhibit the activity of ROCK I (AA 6-553) using standard system associated enzyme (Fox et al. (1998) Protein Sci 7, 2249). The reaction was performed in a solution containing 100 mm HEPES (pH 7.5), 10 mm MgCl2, 25 mm NaCl, 2 mm DTT and 1.5% DMSO. The final substrate concentration in the analysis were 45 μm ATP (Sigma Chemicals, St Louis, MO) and 200 μm peptide (American peptide, Sunnyvale, CA). The reaction was carried out at 30°and 45 nm ROCK I. the Final concentrations of the components of the system associated enzyme were 2.5 mm of phosphoenolpyruvate, 350 μm NADH, 30 μg/ml pyruvate kinase and 10 μg/ml lactate dehydrogenase.

Found that some compounds of the invention inhibit ROCK.

Example 9: analysis of the inhibition of JAK3

Inhibition of compounds JAK analyzed by the method described G.R. Brown, et al., Bioorg. Med. Chem. Lett. 2000, vol. 10, pp. 575-579, as follows. In tablets Maxisorb, pre-coated with 4°poly (Glu, Ala, Tyr), 6:3:1, then washed with 0.05% of a phosphate buffered saline and tween (PBST), add 2 μm ATP, 5 mm MgCl2and a solution of the compound in DMSO. The reaction of the starting enzyme JAK and tablets incubated for 60 minutes at 30°C. the Tablets are then washed with PBST, 100 µl of HRP-conjugate antibody 4G10 and the plate is incubated for 90 minutes at 30°C. the plate again washed with PBST, was added 100 μl of the races is the thief of TMB and tablets incubated for a further 30 minutes at 30° C. To stop the reaction, add sulfuric acid (100 μl of 1 M) and the plate is read at 450 nm to obtain optical densities for analysis to determine values of Ki.

Found that the compounds inhibit JAK-3.

Analysis of inhibition of PDK-1

Screening of the compounds was performed on their ability to inhibit PDK-1, using the analysis of the inclusion of radioactive phosphate (Pitt and Lee, J. Biomol. Screen., (1996), 1, 47). The analysis was carried out in a mixture of 100 mm HEPES (pH 7.5), 10 mm MgCl2, 25 mm NaCl, 2 mm DTT. The final substrate concentration in the analysis were 40 μm ATP (Sigma Chemicals) and 65 μm peptide (PDKtide, Upstate, Lake Placid, NY). The analysis was carried out at 30°and 25 nm PDK-1 in the presence of ˜27,5 NCI/μl [γ-32P]ATP (Amersham Pharmacia Biotech, Amersham UK). Received source buffer solution for analysis, containing all of the reagents listed above, with the exception of ATP and interest of the test compounds. 15 ál of the solution were placed in a 96-well plate followed by addition of 1 μl of 0.5 mm source DMSO solution containing the test compound (final concentration 25 μm, final concentration of DMSO 5%). The tablet is pre-incubated for 10 minutes at 30°and the reaction was initiated by adding 4 μl of ATP (final concentration 40 mm).

The reaction was stopped after 10 minutes by adding 100 μl of 100 mm phosphoric acid,0.01% tween-20. Phosphocellulose 96-well plate (Millipore, Cat. No. NAPHNOB50) was pre-treated with 100 μl of 100 mm phosphoric acid, 0.01 tween-20 before adding the reaction mixture (100 μl). Spots left for impregnation for at least 5 minutes before stage washing (4 × 200 μm 100 mm phosphoric acid, 0.01% tween-20). After drying to the well was added 20 μl of liquid scintillation cocktail Optiphase "SuperMix" (Perkin Elmer) before scintillation counting (1450 Microbeta Liquid Scintillation Counter, Wallac).

Connection detecting more than 50% inhibition versus standard wells containing a mixture of analysis and DMSO without test compounds were titrated to determine the values of the IC50.

Compounds of the invention were tested and it was found that they inhibit PDK-1.

1. The compound of the formula:

or its pharmaceutically acceptable salt,

where R1represents hydrogen;

R2represents a -(T)nAr1where n is 0; Ar1represents a substituted phenyl;

where Ar1are replaced with x independent groups Q-Rxwhere x is 1-3, Q is a bond or C1-6-alkylidenes a circuit in which up to two methylene units of Q optionally replaced by-NR-, -O-, -CO, -CONR-, -NRCO-, -SO2NR-; each Rxis independently R', halogen, NO2, CN, OR', N(R')2, COR', CO2R', CON(R')2, SO2R' or SO2N(R')2where at least one Q-Rxis not hydrogen;

R3linked to the nitrogen atom either in 1-or 2-position of the ring and represents a -(L)mAr2; m is 0; Ar2represents an optionally substituted aryl group selected from pyridine, pyrimidine, thiazole or 9-10-membered bicyclic ring having 1-2 heteroatoms independently selected from nitrogen or sulfur; where Ar2independently, optionally substituted by a group Z-Rywhere y is 0-3, Z is a bond or C1-6-alkylidenes a circuit in which up to two methylene units of Z optionally replaced by-NR-, -O-, -CO -, or-CONR-; in each case, Ryrepresents independently R', halogen, CN, OR', SR', N(R')2, CO2R', CON(R')2or SO2R';

each R independently represents hydrogen or C1-6alkyl group, or benzyl group;

each R' independently represents hydrogen or a group selected from C1-6alkyl group, a 3-7-membered saturated or fully unsaturated monocyclic ring having 0-2 heteroatoms independently selected from nitrogen or sour the ode, where this alkyl group or a monocyclic ring optionally substituted C1-3alkyl group, benzyl group, CH2He, HE, NH2N(CH3)2, CN, F, Cl, cyclopropyl, acetyl, C(O)OS1-2alkyl group, pyrrolidinyl or morpholino or two instances of R' taken together with the atom to which they relate, with the formation of a 5-6-membered saturated or fully unsaturated monocyclic ring having 0-2 heteroatoms independently selected from nitrogen or oxygen, where the aforementioned monocyclic ring is optionally substituted with halogen;

provided that

a) when R3represents pyridyl, then R2is not phenyl, simultaneously substituted by one OMe group in metaprogram and one group of oxazole in paraprotein;

b) when R3represents an unsubstituted pyrimidinyl, then R2is not unsubstituted phenyl, para-OMe-substituted phenyl, para-OEt-substituted phenyl or ortho-OMe-substituted phenyl.

2. The compound according to claim 1, where (L)mAr2selected from one of the following groups:

where any substitutable carbon atom or nitrogen is optionally substituted by ZRy.

3. The compound according to claim 1, where -(L)mAr2represents an optionally substituted 2-pyridyl, 2-thiazolyl, 2-pyrimidinyl, 6-pyrimidinyl, 4-pyridyl, benzothiazolyl or 2-chinoline and compounds have one of the structures, II-F-(i), (II-G-(i), II-G'-(i), (II-I-(i), (II-I'-(i), (II-J-(i)n-G'(i)', II-H-(i)', II-I-(i)', II-I'-(i)' or II-J-(i)':

where n is 0.

4. The compound according to claim 1, where -(L)mAr2represents pyridyl, pyrimidinyl, chinoline or thiazolyl, each of which is optionally substituted by 1-2 groups ZRY.

5. The compound according to claim 4, where x is 1-3, y is 0-2, and in each case QRXor ZRYrepresents independently R', halogen, CN, NO2, -N(R')2, -CH2N(R')2, -OR', CH2OR', -SR', -CH2SR', -COOR', -NRCOR', - CON(R')2, SO2N(R')2, -CONR(CH2)2N(R')2, -CONR(CH2)3N(R')2, -O(CH2) 2OR, -O(CH2)3OR', -O(CH2)2N(R')2, O(CH2)3N(R')2or-O(CH2)4N(R')2.

6. The compound according to claim 1, having one of the formulas:

or

7. The connection according to claim 6, where x is 1-3, y is 0-2, and in each case QRXor ZRYrepresents independently R', halogen, CN, NO2, -N(R')2, -OR', CH2OR', -SR', -CH2SR', -COOR', -NRCOR', -CON(R')2, -SO2N(R')2, -CONR(CH2)2N(R')2, -CONR(CH2)3N(R')2, -O(CH2)2OR', -O(CH2)3OR', -O(CH2)4OR', O(CH2)2N(R')2, -O(CH2)3N(R')2or-O(CH2)4N(R')2.

8. A method of inhibiting the activity of kinases FLT-3 or KIT in a biological sample in vitro, including the state of engagement of the specified biological sample with a compound according to any one of claims 1 to 7.

9. The use of compounds according to any one of claims 1 to 7 for the manufacture of a medicinal product, suitable for treating or alleviating the severity of the disease or condition selected from acute myelogenous leukemia, acute promyelocytic leukemia and acute lim is azotnogo leukemia or cancer of the ovary.

10. The use according to claim 9, where the disease is selected from acute myelogenous leukemia, acute promyelocytic leukemia or acute limfotsitov leukemia.

11. The use according to claim 9, where the disease is ovarian cancer.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention offers analogues of quinazoline of the formula I

where A is bound at least with one of atoms of carbon in position 6 or 7 of the dicyclic ring; X represents N. A represents the group Q or Z including tautomeric group Z form where Q and Z, have the formulas resulted more low in which symbols and radicals, have the value specified in item 1 of the formula of the invention. R1 represents phenyl, substituted -(G)nOAr or -O(G)nAr and where phenyl is unessentially replaced by halogen or C1-C10alkyl; where G represents C1-C4alkylene, n is peer 0 or 1. And Ar represents phenyl either pyridyl or thiazolyl where Ar is unessentially substituted by 1-2 substituents chosen from halogen or C1-C10alkyl; R2 and R3 represent N. The bonds of the formula I are inhibitors of the receptor tyrosine kinases of type 1. The invention includes also a way of treatment of hyperproliferative diseases, such as a cancer, application of bonds of the formula 1 in manufacture of medical products and pharmaceutical composition on the basis of these bonds.

EFFECT: rising of efficiency of a composition and the method of treatment.

14 cl, 6 dwg, 63 ex

FIELD: chemistry.

SUBSTANCE: compounds of the invention have chemokine antagonistic properties and can be applied in treatment of immunoinflammatory diseases, such as atherosclerosis, allergy diseases. In general formula (I) R1 is hydrogen atom, (C1-C4)-alkyl, (C1-C4)-alkoxyl, cyclopropylmethoxy group, (C1-C4)-alkylthio group; R2 is halogen atom, (C1-C8)-alkyl, perfluoro-(C1-C4)-alkyl, (C3-C10)-cycloalkyl, phenyl, (C1-C8)-alkoxyl, values of the other radicals are indicated in the claim of the invention.

EFFECT: improved properties.

14 cl, 7 tbl, 20 dwg, 17 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I) and their pharmaceutically acceptable salts. Claimed compounds have antibacterial effect. In formula (I) , X is ; R1 is i) hydrogen, ii) (CH2)nNR5R6, iv) NRCO2R, v) (C1-6alkyl)CN, CN, (CH2)pOH; Y is NR*, O or S(O)p; is phenyl or 5-6-member heteroaryl with N or S as heteroatoms; R3 is NR(C=X2)R12, NR*R12, or -(O)n-5-6-member heteroaryl with 1-3 heteroatoms selected out of N, O, which can be linked over either carbon atom or heteroatom; the indicated 5-6-member heteroaryl can be optionally substituted by 1-3 groups of R7; R4, R4a, R4b and R4c are independently i) hydrogen, ii) halogen; other radicals are defined in the claim.

EFFECT: pharmaceutical composition containing effective volume of the claimed compound.

13 cl, 1 dwg, 194 ex

FIELD: chemistry.

SUBSTANCE: invention concerns benzothiazole derivatives of general formula (1) and their pharmaceutically acceptable acid-additive salts as adenosine receptor ligands with high affinity to A2A adenosine receptor, and based medicine. Compounds can be applied in treatment and prevention of diseases mediated by A2A adenosine receptors, such as Alzheimer's disease, some depressive states, toxicomania, Parkinson's disease. In general formula (I) , R is C5-C6-cycloalkyl non-substituted or substituted by hydroxy group, or is ethyl or isobutyl, or is tetrahydropyrane-4-yl or -(CH2)n-tetrahydrofurane-2 or 3-yl or is 5-hydroxybicyclo[2,2,1]hept-2-yl; X is CH or N; n is 0 or 1.

EFFECT: enhanced efficiency of composition and treatment method.

12 cl, 2 dwg, 14 ex

FIELD: chemistry.

SUBSTANCE: invention concerns method of treatment, alleviation and/or prevention of neurological state, particularly neurodegenerative disorders, involving administration of effective quantity of compound with formula I: . Also invention concerns application of compound of the formula I as neurotherapeutical, neuroprotective or antimyloid agent, pharmaceutical or veterinary composition for treatment, alleviation and/or prevention of neurological states, and compounds of the formula I on the following additional terms: (b) if R3, R and R' are H, and R2 is (CH2)2NR9R10, then both R9 and R10 are not ethyl or methyl; (c) if R3, R and R' are H, and R2 is (CH2)2NR9R10, then both R9 and R10 are not hydrogen or ethyl; (d) if R3, R and R' are H, and R2 is NR11R12, then both R11 and R12 are not hydrogen; (e) if R3, R and R' are H, and R2 is COR6, then R6 is not H, OH or CH2Cl; (f) if R3, R and R' are H, and R2 is not CH3 or CH2Cl; (g) if R3, R and R' are H, and R2 is HCNN R9R10, then both R9 and R10 are not H.

EFFECT: efficient treatment, alleviation and prevention of neurological state.

24 cl, 14 tbl, 21 ex, 14 dwg

FIELD: chemistry.

SUBSTANCE: invention concerns compounds of the formula I , where R0 is 1) monocyclic 6-14-member aryl, where aryl is independently mono-, di- or trisubstituted by R8, 2) heterocyclyl out of group of benzothiazolyl, indazolyl, pyridyl, where the said heterocyclyl is independently non-substituted or mono-, di- or trisubstituted by R8, and other radicals referred to in point 1 of the claim; R8 is halogen; on condition that R8 is at least one halogen atom if R0 is monocyclic 6-14-member aryl; substructure in the formula I is 4-8-member saturated, partly non-saturated or aromatic cyclic group including 0, 1 heteroatom selected out of nitrogen or sulfur, and is non-substituted or substituted 1, 2, 3 times by R3; Q is -(C0-C2)alkylene-C(O)NR10-, methylene; R1 is hydrogen atom, -(C1-C4)alkyl, where alkyl is non-substituted or substituted one to three times by R13; R2 is a direct link; R1-N-R2-V can form 4-8-member cyclic group selected out of piperazine or piperidine group; R14 is halogen, =O, -(C1-C8)alkyl, -CN; V is 1) 6-14-member aryl, where aryl is independently non-substituted or mono-, di- or trisubstituted by R14, and other radicals referred to in point 1 of the claim; G is direct link, -(CH2)m-NR10, where m is 0 and R10 is hydrogen, -(CH2)m-C(O)-(CH2)n-, where m is 0 or 1, and n is 0, -(CH2)m-C(O)-NR10-(CH2)n-, where m is 0 or 1, and n is 0, 1 or 2, -(CH2)m-, where m is 1; M is 1) hydrogen atom, 2) 6-14-member aryl, and other radicals referred to in point 1 of the claim; R3 is 1) hydrogen atom, 2) halogen atom, 3) -(C1-C4)alkyl, where alkyl is non-substituted, and other radicals referred to in point 1 of the claim; R11 and R12 are independently the same or different and are 1) hyfrogen atom, 2) -(C1-C6)alkyl, where alkyl is non-substituted or monosubstituted by R13, and other radicals referred to in point 1 of the claim; or R11 and R12 can form 4-8-member monocyclic heterocyclic ring together with nitrogen atoms to which they are linked, and beside the nitrogen atom the ring can include one or two similar or different ring heteroatoms selected out of oxygen, sulfur and nitrogen; where the said heterocyclic ring is independently non-substituted or mono-, disubstituted by R13; R13 is halogen, =O, -OH, -CF3, -(C3-C8)cycloalkyl, -(C0-C3)alkylene-O-R10; R10 is hydrogen, -(C1-C6)alkyl; R15 and R16 are independently hydrogen, -(C1-C6)alkyl; R17 is -(C1-C6)alkyl, -(C3-C8)cycloalkyl; in all stereoisomer forms and their mixes at any ratio, and physiologically tolerable salts. Compounds of the formula I are reversible inhibitors of enzyme factor Xa (FXa) and/or factor VIIa (FVIIa) of blood clotting, and can be generally applied in states accompanied by undesirable factor Xa and/or factor VIla activity, or supposing factor Xa and/or factor VIla inhibition for treatment or prevention. In addition, invention concerns methods of obtaining compounds of the formula I, their application as agents in pharmaceutical compositions.

EFFECT: obtaining compounds applicable as agents in pharmaceutical compositions.

19 cl, 1 tbl, 169 ex

FIELD: chemistry.

SUBSTANCE: description is given of a piperidine derivative with general formula (I) , where L represents CH or N; M represents CH or N; under the condition that, L and M both do not represent CH; R1 represents phenyl (possibly substituted with a halogen or C1-4alkyl), S(O)2(C1-4alkyl), S(O)2(C1-4fluroalkyl), S(O)2phenyl (possibly substituted with CF3 or OCF3), benzyl, benzoyl (possibly substituted with a halogen) or C(O)NHphenyl (possibly substituted with a halogen); R2 represents phenyl, possibly substituted with a halogen; R3 represents hydrogen or C1-4alkyl; R4 represents methyl or ethyl; R5 represents phenyl-NH, phenyl (C1-2alkyl), phenyl(C1-C2)alkyl-NH or pyridyl(C1-2alkyl). The phenyl can be substituted with a halogen, cyano, C1-4alkyl, C1-4alkoxy, S(O)k(C1-4alkyl) or S(O)2NR8R9; k is equal to 2; R8 and R9 represent hydrogen or its pharmaceutical salts. The compound is a modulator of the activity of the CCR5 receptor. Description is given of the method of obtaining the compound, where L represents N, and the pharmaceutical composition based on a compound with formula (I).

EFFECT: design of a method of obtaining a compound, where L represents N, and a pharmaceutical composition based a compound with formula (I).

7 cl, 7 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to derivatives of 4-[1-arylimidazol-4-yl ethynyl]-2-alkylpyridine and 4-[1-heteroarylimidazol-4-yl ethynyl]-2-alkylpyridine of general formula I having general formula I in which R1 stands for C1-C6alkyl; R2 stands for C1-C6alkyl or C3-C12cycloalkyl; R3 stands for aryl or heteroaryl, where aryl or heteroaryl are unsubstituted or contain substituents, selected from group, including halogen, C1-C6alkyl, S-C1-C6alkyl, C1-C6alkylhlogen, C1-C6alkoxygroup, halogen- C1-C6lkoxygroup, C3-C12cycloalkyl, C2-C11heterocycloakyl, C1-C6alkylminogroup,di- C1-C6alkylaminogroup, C1-C6alkoxyaminogroup, (C1-C6 alkoxy) C1-C6alkylaminogroup, C3-C12cycloalkylaminogroup, benzylaminogroup and cyanogroup, where said "aryl" represents phenyl, and said " heteroaryl" represents aromatic 5- or 6- member ring or one or more condensed rings, containing one or more heteroatoms, selected from group, which includes nitrogen, oxygen and sulfur; and R4 stands for hydrogen, C(O)H or CH2R5 , where R stands for hydrogen or its pharmaceutically acceptable salt. Invention also relates to method of obtaining compounds of general formula I, their application as anxiolytic, to based on them pharmaceutical composition and method of treatment or prevention of disorders, fully or partly mediated by metabotropic glutamate receptor of subtype 5.

EFFECT: obtaining novel heterocyclic compounds possessing useful biological properties.

15 cl, 18 ex

FIELD: medicine; pharmacology.

SUBSTANCE: compounds of this invention possess properties of protein kinase inhibitors. In the general formula p means integer within 0 to 2; R and R1 mean O; A1 and A2 mean single bond, (C1-C6)alkyl; B2 means monocyclic or bicyclic, saturated or unsaturated heterocyclic radical including 1 to several identical or different heteroatoms, chosen among O, S, N and NR7, probably substituted with one or several identical or different substitutes.

EFFECT: inhibiting effect on protein kinase, effective application of compounds of formula for medical products.

49 cl, 1 tbl, 6 dwg, 334 ex

FIELD: chemistry.

SUBSTANCE: in general formula I

R1 is phenyl or 5-6-member heterocycle, containing one N atom and/or one O atom; R2 is imidazole or annelated imidazole, selected from group, including a), b), c), d) and e); and R3 stands for hydrogen, phenyl, 2,3-dihydrobenzo[1,4]dioxin-6-yl, benzo[b]thiophen-3-yl, 3-methylbenzo[b] thiophen-2-yl, thiophen-2-yl or thiophen-2-ylmethyl, R4 is hydrogen or lower alkyl, R5 is hydrogen, lower alkyl, halogen, morpholinyl, -NR'R", piperydinyl, optionally substituted with hydroxy-group, or is pyrrolidin-1-yl; R6 is hydrogen or -(CH2)nO-lower alkyl, R7 is hydrogen, -C(O)O-lower alkyl, -C(O)-C6H4-halogen, -C(O)-C6H4-lower alkyl, -C(O)-lower alkyl, -C(O)-cycloalkyl, -C(O)-NR'R", -C(O)-(CH2)nO-lower alkyl, -S(O)2-lower alkyl, -(CH2)nO-lower alkyl, -C(O)-pyridin-4-yl, whose ring can contain as substituents lower alkyl, halogen-lower alkyl or pyrrolidin-1-ylmethyl or is -(CH2)n-C(O)-NR'R"; R'/R" independently on each other stand for hydrogen, lower alkyl or -(CH2)n-tetrahydropyran-4-yl, X is -CH2-, -NR'''- or -O-; R''' is hydrogen, -C(O)-lower alkyl, -C(O)O-lower alkyl, -C(O)-C6H4CH3 or benzyl; n is 1 or 2.

EFFECT: increase of composition and treatment method efficiency.

14 cl, 56 ex

FIELD: medicine.

SUBSTANCE: invention offers analogues of quinazoline of the formula I

where A is bound at least with one of atoms of carbon in position 6 or 7 of the dicyclic ring; X represents N. A represents the group Q or Z including tautomeric group Z form where Q and Z, have the formulas resulted more low in which symbols and radicals, have the value specified in item 1 of the formula of the invention. R1 represents phenyl, substituted -(G)nOAr or -O(G)nAr and where phenyl is unessentially replaced by halogen or C1-C10alkyl; where G represents C1-C4alkylene, n is peer 0 or 1. And Ar represents phenyl either pyridyl or thiazolyl where Ar is unessentially substituted by 1-2 substituents chosen from halogen or C1-C10alkyl; R2 and R3 represent N. The bonds of the formula I are inhibitors of the receptor tyrosine kinases of type 1. The invention includes also a way of treatment of hyperproliferative diseases, such as a cancer, application of bonds of the formula 1 in manufacture of medical products and pharmaceutical composition on the basis of these bonds.

EFFECT: rising of efficiency of a composition and the method of treatment.

14 cl, 6 dwg, 63 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I) and their pharmaceutically acceptable salts. Claimed compounds have antibacterial effect. In formula (I) , X is ; R1 is i) hydrogen, ii) (CH2)nNR5R6, iv) NRCO2R, v) (C1-6alkyl)CN, CN, (CH2)pOH; Y is NR*, O or S(O)p; is phenyl or 5-6-member heteroaryl with N or S as heteroatoms; R3 is NR(C=X2)R12, NR*R12, or -(O)n-5-6-member heteroaryl with 1-3 heteroatoms selected out of N, O, which can be linked over either carbon atom or heteroatom; the indicated 5-6-member heteroaryl can be optionally substituted by 1-3 groups of R7; R4, R4a, R4b and R4c are independently i) hydrogen, ii) halogen; other radicals are defined in the claim.

EFFECT: pharmaceutical composition containing effective volume of the claimed compound.

13 cl, 1 dwg, 194 ex

FIELD: chemistry.

SUBSTANCE: in compound of formula I , R1 is hydrogen; R2 is phenyl substituted by trifluoromethyl and optionally by other substitute selected out of a group including lower hydroxyl alkyl, lower alkylamino, lower hydroxyl alkylamino, dilower alkylamino, 1H-imidazolyl, lower alkyl-1H-imidazolyl, carbamoyl, lower alkylcarbamoyl, pyrrolidino, piperazino, lower alkylpiperazino, morpholino, lower alkoxy, trilfuoro-lower alkoxy, phenyl, pyridyl and halogenyl; R4 is methyl; where 'lower' prefix denotes radical with up to 7 carbon atoms. Also invention concerns pharmaceutical composition and method of treatment, as well as application of the claimed compounds in obtaining pharmaceutical composition.

EFFECT: improved proteinkinase inhibition properties.

9 cl, 98 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to new macrocyclic compounds with formula (I): (where R3, R6, R7 and R21 can be identical or different from each other, and each of them assume values given in the description), their salts used in pharmacology and their hydrate. Compounds with formula (I) are capable of inhibiting angiogenesis, particularly VEGF production in hypoxic conditions, and can be used as therapeutic means of treating solid malignant tumours. The invention also relates to medicinal agents based on these compounds, prevention and treatment method and use of these compounds in making preparations for preventing and treating cancerous diseases.

EFFECT: obtaining compounds, capable of inhibiting angiogenesis, particularly VEGF production in hypoxic conditions, which can be used as therapeutic means of treating solid malignant tumours.

35 cl, 3 tbl, 147 ex