Naphtylene derivative as cytochrome p450 inhibitors

FIELD: chemistry.

SUBSTANCE: present invention refers to the new naphtylene derivative having general formula (I-A) and to their pharmaceutically acceptable salts having the property of inhibition of the cytochrome ferment P450RAI (Cyp26) activity, to the pharmaceutic composition thereof and to the method of inhibition of cytochrome ferment P450RAI (Cyp26). , wherein X is selected from imidasolyl or triasolyl; R2 and R3, independently represent H, C1-10-alkyl; G1 is -NR72R82 or G1 and R3 taken together with attached carbon atom form 3-10-membered saturated ring or heterocyclic saturated ring containing N as heteroatom which is optionally substituted with substituting group R72, Z, R4b, R5b, Q1, R72, n2, n3 and n4 values are indicated in the formula of the invention.

EFFECT: present invention refers to the intermediates for compounds with general formula (I-A) and to their pharmaceutic salts thereof.

37 cl, 30 dwg, 7 tbl

 

The prior art INVENTIONS

This invention relates to new heteroaryl-naphthalenyl-alkylamines followed, their salts, processes for their preparation and compositions containing them. New connections are used for inhibition of the enzyme cytochrome P450RAI (Cyp26) in animals, including humans, for the treatment and/or prevention of various diseases and conditions that respond to treatment by retinoids and natural retinoic acid.

In this area it is known that retinoic acid, retinoid-like compounds and pharmaceutical compositions containing retinoic acid or retinoid-like compounds as the active ingredient, play a significant role in the regulation and differentiation of epithelial cells. Such regulatory and differentiating effects, which include the ability to stimulate cell differentiation, apoptosis and inhibition of cell proliferation, make the retinoic acid and retinoid compounds useful in the treatment of tumors and in the treatment of conditions such as skin diseases. Retinoids and retinoid compounds known as a treatment for skin disorders such as senile keratoses, arsenic keratoses, inflammatory and non-inflammatory acne, psoriasis, ichthyosis, keratinization and hyperproliferative skin diseases, eczema, atopic the cue dermatitis, disease Daria, planus; for the prevention, treatment, and changes the current glucocorticoid, age-related skin damage and fotoparatu skin. Retinoids and retinoid compounds are also known as local antimicrobial and skin ANTIMIGRAINE funds. Retinoids due to their action as a differentiating means contribute to the restoration of the normal phenotype of the cells and therefore can modify or suppress the development of malignant changes or even to prevent cancer invasion. So retinoid compounds are used for the prevention and treatment of cancerous and precancerous conditions, including, premalignant and malignant hyperproliferative diseases such as cancer of the breast, skin, prostate, rectum, bladder, cervix, uterus, stomach, lung, esophagus, blood and lymphatic system, larynx, oral cavity, metaplasia, dysplasia, neoplasia, leukoplakia and papilloma of the mucous membranes in the treatment of Kaposi's sarcoma. In addition, retinoid compounds can be used as tools for the treatment of diseases of the eye, including, for example, a proliferative vitreoretinopathy, retinal detachment, Corporatio, such as dry eyes, as well as for treatment and prevention of various cardiovascular diseases, including the common the disease, associated with lipid metabolism, such as dyslipidemia, not limited to the aforementioned, prevention of restenosis after angioplasty, and as a means of increasing the level of tissue plasminogen activator in circulation. Other applications of retinoid compounds include the prevention and treatment of conditions and diseases associated with human papilloma virus (HPV), including warts, various inflammatory diseases such as pulmonary fibrosis, REIT, colitis and Crohn's disease, neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and "kick"disturbed pituitary function, including insufficient production of growth hormone, modulation of apoptosis, including induction of apoptosis, restoration of hair growth, including combination therapies with these connections and other means, such as Minoxidil®, diseases associated with the immune system, including the use of these compounds as immunosuppressants and Immunostimulants, modulation rejection of an organ transplant and stimulation of wound healing, including modulation calosa. Also found that retinoid compounds should be used in the treatment of non-insulin dependent diabetes mellitus type II (NIDDM).

Some compounds, characterized by a retinoid-like activity after with the corresponding proper approval in the United States of America and in other countries are sold as medicines for the treatment of several diseases, treatable by retinoids. Itself retinoic acid (RA) is a natural retinoid, biologically most active metabolite of vitamin a, biosynthesized and is present in large quantities in the tissues of humans and mammals and is known to play a significant role in the regulation of gene expression, cellular differentiation, proliferation of epithelial cells and in other important biological processes in mammals, including humans.

Retinoids cause reversion of malignant growth in vivo and in vitro and act as chemoprophylactic funds. Retinoids can be used successfully for the treatment of leukoplakia of the oral cavity, potentially precancerous mucosal injury, and they can inhibit or slow down the appearance of the primary multiple tumors followed by squamous cell cancer of the head and neck (HNSCC). Mentioned plurality of primary tumors, which occurs with a frequency of 2-3% per year, is the leading cause of death after surgical resection of malignant tumors of the head and neck at the initial stage. Retinoid therapy is also used in the treatment of glioma tumors, primary and metastatic melanoma cells, and retinoids exhibit antimetastatic activity in invasive cell adenocarcinoma of the prostate of the rat. Retinoid therapy of leukemia has loads is established through the terminal differentiation and the possible apoptotic death of leukemia cells and as shown, leads to complete remission in up to 90% of patients with acute proliferative leukemia (APL).

Although treatment with retinoids effectively induces complete remission in APL, when using only retinoids, in most patients there is a relapse within a few months. Clinical application of retinoic acid for the treatment of cancer largely prevents rapid emergence of resistance, which is believed due to the increased metabolism of retinoic acid. Retinoic acid is metabolized Cyp26A1 (Cyp26), induced by the enzyme cytochrome P450, which inactivates RA, oxidizing RA up to 4-HO-atRA, 8-HO-atRA and 4-oxo-atRA. Tightly controlled by a negative feedback mechanism limits the availability of RA and, therefore, limits its biological activity. The identified compounds that inhibit Cyp26 and, therefore, the metabolism of RA and, as shown, enhance the antiproliferative effects of RA and cause an increase in endogenous levels of RA in plasma and in tissues.

Cyp26 inhibitors, also known as a means of blocking the metabolism of retinoic acid (RAMBAs)described and include, for example, liarozole (lieselTMand R116010. Such Cyp26 inhibitors demonstrate therapeutic efficacy in dermatology and cancer in vitro, in vivo and in the clinic is a mini-applications. Some preclinical tumor models lioresal exerts its anticancer properties that correlate with reduced metabolism of endogenous retinoic acid and, consequently, with the increase of RA accumulation in tumor cells. It is shown that in cancer patients lioresal increases the half-life of oral introduced RA and 13-CIS-RA. Unfortunately, one of the limitations of application of liarozole and many of Cyp26 inhibitors described in the literature, is the lack of specificity. Liarozole, and other Cyp26 inhibitors inhibit other mediated by the cytochrome P450 reaction, and restriction of their use due to the lack of specificity in relation to other cytochrome P450 enzymes. Mentioned lack of specificity may explain the limited frequency of favorable ratio (FDA considers unsatisfactory ratio of the activity/toxicity)observed in patients with prostate cancer in phase III clinical trials liarozole. Therefore, there is a clear need for Cyp26 inhibitors within retinoid therapy, which would be highly efficient and selective and which showed higher selectivity against other cytochrome-P450-enzymes, fewer side effects and would have a favorable drug-like properties, including sufficient rest remote in water, bioavailability satisfactory pharmacokinetic properties, coefficients of extraction and limited toxicity to balance the ratio of the activity/toxicity and for use in the treatment of various dermatological diseases and cancers.

In the present invention are highly effective and selective new heteroaryl-naphthalenyl-alkylamines followed, Cyp26 inhibitors, which provide therapeutic effectiveness in the treatment or prevention of diseases and conditions that respond to treatment by retinoids or regulated natural retinoic acid. Set the mode of action of the above-mentioned compounds is that as a result of inhibition of the enzyme Cyp26 (CP450RAI [cytochrome P450-induced retinoic acid]), which, as shown in this area, catabolized natural retinoic acid, increasing the endogenous levels of retinoic acid up to a level that achieves the desired therapeutic efficacy. Endogenous levels of natural and synthetic retinoids, which are metabolized Cyp26, as expected, increase in the inhibition of Cyp26 new heteroaryl-naphthalenyl-bonds alkylamines, Cyp26 inhibitors described in this invention. The simultaneous introduction of the composition of natural or synthetic retinoids with connection what changes or their pharmaceutically suitable salts, described in this invention can increase the level of retinoids. The simultaneous introduction of natural and synthetic retinoids, which catabolized Cyp26, at least one compound described in this invention is a method of treating skin or cancer, which provides a higher endogenous levels of retinoids. The compounds of this invention are active at nanomolar concentrations and selectively and effectively inhibit the enzymes involved in the catabolism of retinoic acid, and therefore lead to effective change desired levels of atRA.

The following publications describe or establish the role of Cyp26 inhibitors and their ability to slow down the catabolism of retinoic acid, thus, to increase endogenous levels of retinoic acid and their potential for the treatment of dermatological diseases and cancers:

Altucci, L. et.al. “Retinoic Acid-induced Apoptosis in Leukemia Cells is Mediated by Paracrine Action of Tumor-Selective Death Ligand Trail”,Nature Med.2001,7, 680-686;

Altucci, L.; Gronemeyer, H. “The Promise of Retinoids to Fight Against Cancer”, Nature Reviews (Cancer),2001, 1, 181-193;

Winum, J. Y.; et. al. “Synthesis of New Targretin®Analogues that Induce Apoptosis in Leukemia HL-60 Cells”, Bioorganic & Medicinal Chemistry Letters,2002, 12, 3529-3532.

Kuijpers, et. al. “The Effects of Oral Liarozole on Epidermal Proliferation and Differentiation in Severe Plaque Psoriasis are Comparable with Those of Acitretin”, British Journal of Dermatology,1998. 139, 380-38;

Van Wauwe, et. al. “Liarozole, an Inhibitor of Retinoic Acid Metabolism, Exerts Retinoid-Mimetic Effects in Vivo”, The Journal of Pharmacology and Experimental Therapeutics,1992, 261, 773-779.

Haque, M.; Andreola, F.; DeLuca, L. M. “The Cloning and Characterization of a Novel Cytochrome P450 Family, Cyp26, with Specificity towards Retinoic Acid”,Nutri Rev.1999,56, 84-85.

Wouters, W. et. al. “Effects of Liarozole, a New Antitumoral Compound and Retinoic Acid-Induced Inhibition of Cell Growth and on Retinoic Acid Metabolism in MCF-7 Breast Cancer Cells”,Cancer Res,1992,52, 2841-2846;

Freyne, E. et. al. “Synthesis of Liazal™, a Retinoic Acid Metabolism Blocking Agents (RAMBA) with Potential Clinical Applications in Oncology and Dermatology”,Bioorganic & Medicinal Chemistry Letters,1998,8, 267-272;

Miller, W. H. “The Emerging Role of Retinoids and Retinoic Acid Metabolism Blocking Agents in the Treatment of Cancer”,Cancer,1998,83, 1471-1482;

Van Heusden J. et. al. “Inhibition of all-TRANS-retinoic Acid Metabolism by R116010 Dosage Antitumor Activity”,Br. J. Cancer,2002,86(4), 605-611;

Debruyne, F. J. M. et. al. “Liarozole-A Novel Treatment Approach for Advanced Prostate Cancer: Results of a Large Randomized Trial versus Cyproterone”,Urology,1998,52, 72-81;

De Coster, R. et. al. “Experimental Studies with Liarozole (R75251): An Antitumor Agent which Inhibits Retinoic Acid Breakdown”,J. Steroid Biochem. Molec. Biol.1992,43, 197-201;

Njar, V. C. O.; Brodie, A. M. H. “Inhibitors of Cytochrome P450 Enzymes: Their Role in Prostate Cancer Therapy”, I Drugs, 1999, 1, 495-506;

Miller, V. A.; Rigas, J. R.; Muindi, J. F. R.; Tong, W. P.; Venkatraman, E.; Kris, M. G.; Warrell Jr. R. P. “Modulation of all-trans-retinoic acid pharmacokinetics by liarozole”,Cancer Chemother. Pharmacol.1994,34, 522-526;

Muindi, J.; Frankel, S. R.; Miller Jr. W. H.; It A.; Scheinberg, D. A.; Young, C. W.; Dmitrovski, E.; Warrell, Jr. R. P. “Continuous treatment with all-trans-retinoic acid causes a progressive reduction in plasma rug concentrations: implications for relapse and retinoid 'resistance' in patients with acute promyelocytic leukemia”, Blood.1992,79, 299-303;

Muindi, J F.; Scher, H. I.; Rigas, J. R.; Warrell Jr. R. P.; Young, C. W. “Elevated plasma lipid peroxide content correlates with rapid plasma clearance of all-trans-retinoic acid in patients with advanced cancer”,Cancer Res.1994,54, 2125-2128.

In U.S. patent No. V describe inhibitors of cytochrome P450RAI. In international patent publication no WO 99/29674 consider the inhibitors of the metabolism of retinoic acid. In international patent publication no WO 01/A describe imidazol-4-yl-methanol, used as inhibitors of steroid-C17-20-LiAZ.

In U.S. patent No. 6291677 and 6124330 and international patent publication no WO 02/03912 A2 describe inhibitors of cytochrome P450RAI. In international application number PCT/US00/11833 consider agonists and antagonists of PPAR. In international patent publication no WO 02/06281 describe selective agonists adrenergic receptor-β3. In international patent publication no WO 01/068647 discuss antiviral agent. In international patent publication no WO 01/062234 consider inhibitor farnesyl-protein transferase. In international patent publication no WO 01/055155 describe compounds that exhibit antimicrobial activity. In international patent publication no WO 01/044170 are derivatives of Adamantine. In international patent publication no WO 01/000615 describe the benzimidazole. In international patent publication no WO 00/069843 discuss with the organisations for the treatment of inflammation. In international patent publication no WO 00/043384 describe aromatic heterocyclic urea as anti-inflammatory agents. In Japanese patent publication No. JP 01/43635 present compositions and derivatives of benzimidazole. In international patent publication no WO 99/40092 consider agonists, antagonists or reverse agonists at GABAa. In international patent publication no WO 99/376609 describe verocity used against cytomegalovirus. In German patent publication No. DE 75/6388 offer 2-aryl-4-amino-hintline. In international patent publication WO 98/54168 describe derivatives of 2-accomidate. In international patent publication no WO 98/23593 consider the inhibitors of apolipoprotein b and/or microsomal protein carrier of triglycerides. In U.S. patent No. 5852213 discuss inhibitors of matrix metalloproteinases, MMP-enzymes. In U.S. patent No. 5834483 and international patent publication no WO 97/37665 describe endothelin antagonists. In international patent publication no WO 97/24117 describe compounds substituted hydroxamic acids. In international patent publication no WO 95/29689 consider derivatives of N-carboxyethyl. In U.S. patent No. 5461162 describe an ancillary compound N-acyl. In European patent publication No. 611776 describe pseudopeptide with antiviral activity is. In European patent publication No. 569220 are organic sulfonamides. In European patent publication No. 545376 describe guanidinoacetate. In German patent No. DE 4201435 consider trifluoromethyl-ketones. In German patent No. DE 4138820 describe compounds used as herbicides. In international patent publication no WO 91/19717 consider the phosphodiesterase inhibitor. In European patent publication No. EP 437729 represent retroviral peptide protease inhibitors. In European patent publication No. EP 412350 describe peptides that are inhibitors of renin. In international patent publication no WO 89/10919 are derived barbastella. In international patent publication no WO 00/064888 consider diarilammoniynye acids and their derivatives. In WO 99/47497 describe naphthyl - indolyl-arylsulfonamides. In German patent No. DE 4304650 are benzimidazole, xantina and analogues. In international patent application number PCT/CA99/00212 describe the compounds used for the treatment or prevention of diseases mediated by prostaglandins.

SUMMARY of INVENTION

This invention relates to compounds, which are depicted by the formula I:

and their pharmaceutically suitable salts. The compounds of formula I inhibit f is rment cytochrome P450RAI and their use for the treatment and/or prevention of various diseases and conditions, are treatable by retinoids and natural retinoic acid.

DETAILED description of the INVENTION

This invention relates to the compound of the formula I:

or its pharmaceutically acceptable salts, in which:

X represents the unsubstituted heterocycle selected from pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, thiazolyl or pyridinyl, any of which may replace one or more independent substituents R66;

R1means0-6-alkyl, -OR7, -SR7or-NR7R8;

R2and R3each independently represents a C0-10-alkyl, C2-10alkenyl,2-10-quinil,1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl,1-10-alkoxy-C2-10-quinil,1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl,1-10-alkylthio-C2-10-quinil, cyclo-C3-8-alkyl, cyclo-C3-8alkenyl, cyclo-C3-8-alkyl-C1-10-alkyl, cyclo-C3-8alkenyl-C1-10-alkyl, cyclo-C3-8-alkyl-C2-10alkenyl, cyclo-C3-8alkenyl-C2-10alkenyl, cyclo-C3-8-alkyl-C2-10-quinil, cyclo-C3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl, hetero is iklil-C 2-10-quinil,1-10-alkylsulphonyl,2-10-alkenylboronic,2-10-alkenylboronic,1-10-alkoxycarbonyl,1-10-alkoxycarbonyl-C1-10-alkyl, mono-C1-6-alkylaminocarbonyl, di-C1-6-alkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl or1-10-alkyl(aryl)aminocarbonyl, any of which may replace one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR71R81or-NR71R81; or aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR71C1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR71R81, -SO2NR71R81or-NR71R81; or hetaryl-C0-10-alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR71C1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10/sub> -quinil, -COOH, C1-4-alkoxycarbonyl, -CONR71R81, -SO2NR71R81or-NR71R81;

or R2and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: With1-6-alkyl, halogen, cyano, nitro, -OR71, -SO2NR71R81or-NR71R81; G1means-OR72, -SR72, -NR72R82(R9)n5or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, any of which may replace one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or, in the case of-NR72R82(R9)n5R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring, or heterocyclic is some unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83;

Y represents an oxygen atom, a sulfur atom, -(C=O)N(R74)-, >CR4cR5cor >NR74;

Z means-aryl-, -arylalkyl-, -aryloxy-, -oxyaryl-, -arylalkyl-, -alkynylaryl-, -hetaryl-, -getariako-, -alkylether-, -heterolactic-, -alkenylacyl - or-aryl-, any of which may replace R68;

Q1represents a C0-6-alkyl, -OR75, -NR75R85(R95)n6, -CO2R75, -CONR75R85, -(C=S)OR75, -(C=O)SR75, -NO2, -CN, halogen, -S(O)n6R75, -SO2NR75R85, -NR75(C=NR775)NR7775R85, -NR75(C=NR775OR7775, -NR75(C=NR775)SR7775, -O(C=O)OR75, -O(C=O)NR75R85, -O(C=O)SR75, -S(C=O)OR75, -S(C=O)NR75R85, -S(C=O)SR75, -NR75(C=O)NR775R85or-NR75(C=S)NR775R85; in the case of-NR75R85(R95)n6R75and R85taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, any of which may be substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR76R86or-NR76R86;

R4a, R4b, R4c, R5a, R5band R5ceach independently represents a C0-10-alkyl, C2-10alkenyl,2-10-quinil,1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl,1-10-alkoxy-C2-10-quinil,1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl,1-10-alkylthio-C2-10-quinil, cyclo-C3-8-alkyl, cyclo-C3-8alkenyl, cyclo-C3-8-alkyl-C1-10-alkyl, cyclo-C3-8alkenyl-C1-10-alkyl, cyclo-C3-8-alkyl-C2-10alkenyl, cyclo-C3-8alkenyl-C2-10alkenyl, cyclo-C3-8-alkyl-C2-10-quinil, cyclo-C3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl or heterocyclyl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77With1-10-alkyl, C2-10-alkenyl,2-10-alkini the Ohm, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR77R87, -SO2NR77R87or-NR77R87; or hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR77R87, -SO2NR77R87or-NR77R87; or mono(C1-6-alkyl)amino-C1-6-alkyl, di(C1-6-alkyl)amino-C1-6-alkyl, mono(aryl)amino-C1-6-alkyl, di(aryl)amino-C1-6-alkyl or-N(C1-6-alkyl)-C1-6-alkyl-aryl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR77R87, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5bor R4cwith R5ctaken the e together with the respective carbon atom, to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5bor R4cwith R5ctaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, it called the ring may replace R69;

R6a, R6b, R66, R67, R68and R69each, independently represents halogen, -OR78, -SH, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88C0-10-alkyl, C2-10alkenyl, C2-10-quinil, C1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl, C1-10-alkoxy-C2-10-quinil, C1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl, C1-10-alkylthio-C2-10-quinil, ciclos3-8-alkyl, ciclos3-8alkenyl, ciclos3-8-alkyl-C1-10-alkyl, cyclo-C3-8alkenyl-C1-10-alkyl, ciclos3-8-alkyl-C2-10alkenyl, ciclos3-8alkenyl-C2-10alkenyl, ciclos3-8-alkyl-C2-10-quinil, ciclos3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10 alkenyl or heterocyclyl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR778, -SO2NR778R888or-NR778R888; or aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR778C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR778R888, -SO2NR778R888or-NR778R888; or hetaryl-C0-10-alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR778C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR778R888, -SO2NR778R888or-NR778R888; or mono-(C1-6-alkyl)amino1-6-alkyl, di(C1-6-alkyl)amino1-6-alkyl, mono(aryl)amino1-6-alkyl, di(aryl)amino1-6-alkyl, -N(C1-6-alkyl)-C1-6-alkyl-and the sludge any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR778C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR778R888, -SO2NR778R888or-NR778R888; or in the case of-NR78R88(R98)n7R78and R88taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR778R888or-NR778R888;

R7, R71, R72, R73, R74, R75, R775, R7775, R76, R77, R78, R778, R8, R81, R82, R83, R84, R85, R86, R87, R88, R888, R9, R95and R98each independently represents a C0-10-alkyl, C2-10alkenyl, C2-10-quinil, C1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl, C1-10-alkoxy-C2-10-quinil, C1-10-Ala is ltio-C 1-10-alkyl, C1-10-alkylthio-C2-10alkenyl, C1-10-alkylthio-C2-10-quinil, ciclos3-8-alkyl, ciclos3-8alkenyl, ciclos3-8alkyl-C1-10-alkyl, ciclos3-8alkenyl-C1-10-alkyl, ciclos3-8alkyl-C2-10alkenyl, ciclos3-8alkenyl-C2-10alkenyl, ciclos3-8-alkyl-C2-10-quinil, ciclos3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl, heterocyclyl-C2-10-quinil, C1-10-alkylsulphonyl, C2-10-alkenylboronic, C2-10-alkenylboronic, C1-10-alkoxycarbonyl, C1-10-alkoxycarbonyl-C1-10-alkyl, mono1-6-alkylaminocarbonyl, di-C1-6-alkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl or1-10-alkyl(aryl)aminocarbonyl, any of which may replace one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -O(C0-4-alkyl), C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-and what keniam, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CON(C0-4-alkyl)(C0-10-alkyl), -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); or hetaryl-C0-10-alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -O(C0-4-alkyl), C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CON(C0-4-alkyl)(C0-4-alkyl), -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); or mono(C1-6-alkyl)amino1-6-alkyl, di(C1-6-alkyl)amino1-6-alkyl, mono(aryl)amino1-6-alkyl, di(aryl)amino1-6-alkyl or-N(C1-6-alkyl)-C1-6-alkyl-aryl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -O(C0-4-alkyl), C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CON(C0-4-alkyl)(C0-4-alkyl), -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); and

n1, n2, n3, n4, n5, n6 and n7 each independently 0, 1 or 2.

In the aspect of the present invention consist of a compound of formula I or its pharmaceutically acceptable salt, in which X represents a possibly substituted imidazolyl or perhaps substituted triazolyl, and other variables are as described above.

In the embodiment of this aspect of the present compound of formula I or its pharmaceutically acceptable salt, in which X represents a possibly substituted imidazolyl or substituted triazolyl; R1means hydrogen; and the other variables are as described above.

In the second aspect of the present invention consist of a compound of formula I or its pharmaceutically acceptable salt, in which Y represents oxygen, and other variables are as described above.

In the embodiment of this second aspect of the present compound of the invention, which is depicted by formula I-A:

or its pharmaceutically acceptable salt, in which:

X represents an unsaturated heterocycle selected from pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, thiazolyl or pyridinyl, any of which may replace one or more independent substituents R66;

R2and R3, each is, independently represents a C0-10-alkyl, C2-10alkenyl,2-10-quinil,1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl,1-10-alkoxy-C2-10-quinil,1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl,1-10-alkylthio-C2-10-quinil, cyclo-C3-8-alkyl, cyclo-C3-8alkenyl, cyclo-C3-8-alkyl-C1-10-alkyl, cyclo-C3-8alkenyl-C1-10-alkyl, cyclo-C3-8-alkyl-C2-10alkenyl, cyclo-C3-8alkenyl-C2-10alkenyl, cyclo-C3-8-alkyl-C2-10-quinil, cyclo-C3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl, heterocyclyl-C2-10-quinil,1-10-alkylsulphonyl,2-10-alkenylboronic,2-10-alkenylboronic,1-10-alkoxycarbonyl,1-10-alkoxycarbonyl-C1-10-alkyl, mono-C1-6-alkylaminocarbonyl, di-C1-6-alkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl or1-10-alkyl(aryl)aminocarbonyl, any of which may replace one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR71R81or-NR71R81; or aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, to any of the categories, may replace one or more independent substituents: halogen, cyano, nitro, -OR71C1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR71R81, -SO2NR71R81or-NR71R81; or hetaryl-C0-10-alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR71C1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR71R81, -SO2NR71R81or-NR71R81;

or R2and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: With1-6-alkyl, halogen, cyano, nitro, -OR71, -SO2NR71R81or-NR71R81;

G1means-OR72, -SR72, -NR72R82(R 9)n5or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, any of which may replace one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or, in the case of-NR72R82(R9)n5R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83;

Z means-aryl-, -arylalkyl-, -aryloxy-, -oxyaryl-, -arylalkyl-, -alkynylaryl-, -hetaryl-, -getariako-, -alkylether-, -heterolactic-, -alkenylacyl - or-aryl-, any of which may replace R68;

Q1represents a C0-6-alkyl, -OR75, -NR75R85(R95)n6, -CO2R75, -CONR75R85, -(C=S)OR75, -(C=O)SR75, -NO2 , -CN, halogen, -S(O)n6R75, -SO2NR75R85, -NR75(C=NR775)NR7775R85, -NR75(C=NR775OR7775, -NR75(C=NR775)SR7775, -O(C=O)OR75, -O(C=O)NR75R85, -O(C=O)SR75, -S(C=O)OR75, -S(C=O)NR75R85, -S(C=O)SR75, -NR75(C=O)NR775R85or-NR75(C=S)NR775R85; in the case of-NR75R85(R95)n6R75and R85taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, any of which may replace one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR76R86or-NR76R86;

R4band R5beach independently represents a C0-10-alkyl, C2-10alkenyl,2-10-quinil,1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl,1-10-alkoxy-C2-10-quinil,1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl,1-10-alkylthio-C2-10-quinil, cyclo-C3-8-alkyl, cyclo-C3-8alkenyl, cyclo-C3-8-alkyl-C1-10-alkyl, cyclo-C3-8alkenyl-C1-10-alkyl, cyclo-C3-8-alkyl-C2-10and canil, cyclo-C3-8alkenyl-C2-10alkenyl, cyclo-C3-8-alkyl-C2-10-quinil, cyclo-C3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl or heterocyclyl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR77R87, -SO2NR77R87or-NR77R87; or hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR77R87, -SO2NR77R87or-NR77R87 ; or mono(C1-6-alkyl)amino-C1-6-alkyl, di(C1-6-alkyl)amino-C1-6-alkyl, mono(aryl)amino-C1-6-alkyl, di(aryl)amino-C1-6-alkyl or-N(C1-6-alkyl)-C1-6-alkyl-aryl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR77R87, -SO2NR77R87or-NR77R87; or R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, it called the ring may replace R69;

R66, R67, R68and R69each, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88C0-10-alkyl, C2-10alkenyl, C2-10-kinil, C1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl, C1-10-alkoxy-C2-10-quinil, C1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl, C1-10-alkylthio-C2-10-quinil, ciclos3-8-alkyl, ciclos3-8alkenyl, ciclos3-8-alkyl-C1-10-alkyl, cyclo-C3-8alkenyl-C1-10-alkyl, ciclos3-8-alkyl-C2-10alkenyl, ciclos3-8alkenyl-C2-10alkenyl, ciclos3-8-alkyl-C2-10-quinil, ciclos3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl or heterocyclyl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR778, -SO2NR778R888or-NR778R888; or aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR778C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR778R888, -SO2NR778R888or-NR778R888; or hetaryl-C0-10-alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10 -quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR778C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR778R888, -SO2NR778R888or-NR778R888; or mono-(C1-6-alkyl)amino1-6-alkyl, di(C1-6-alkyl)amino1-6-alkyl, mono(aryl)amino1-6-alkyl, di(aryl)amino1-6-alkyl, -N(C1-6-alkyl)-C1-6-alkyl-aryl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR778C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR778R888, -SO2NR778R888or-NR778R888; or in the case of-NR78R88(R98)n7R78and R88taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: haloge the Ohm, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR778R888or-NR778R888;

R7, R71, R72, R73, R75, R775, R7775, R76, R77, R78, R778, R8, R81, R82, R83, R85, R86, R87, R88, R888, R9, R95and R98each independently represents a C0-10-alkyl, C2-10alkenyl, C2-10-quinil, C1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl, C1-10-alkoxy-C2-10-quinil, C1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl, C1-10-alkylthio-C2-10-quinil, ciclos3-8-alkyl, ciclos3-8alkenyl, ciclos3-8alkyl-C1-10-alkyl, ciclos3-8alkenyl-C1-10-alkyl, ciclos3-8alkyl-C2-10alkenyl, ciclos3-8alkenyl-C2-10alkenyl, ciclos3-8-alkyl-C2-10-quinil, ciclos3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl, heterocyclyl-C2-10-quinil, C1-10-alkylsulphonyl, C2-10-alkenylboronic, C2-10-alkenylboronic, C1-10-alkoxycarbonyl, C1-10-alkoxycarbonyl-C1-10-alkyl, mono1-6-alkylaminocarbonyl, di-C1-6-alkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl or -alkyl(aryl)aminocarbonyl, any of which may replace one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -O(C0-4-alkyl), C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CON(C0-4-alkyl)(C0-10-alkyl), -SO2N(C0-4-alkyl)(C0-10-alkyl), or-N(C0-4-alkyl)(C0-4-alkyl); hetaryl-C0-10-alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -O(C0-4-alkyl), C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CON(C0-4-alkyl)(C0-10-alkyl), -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); or mono(C1-6-alkyl)amino-C1-6-alkyl, di(C1-6alkyl)amino-C 1-6-alkyl, mono(aryl)amino-C1-6-alkyl, di(aryl)amino-C1-6-alkyl or N(C1-6-alkyl)-C1-6-alkyl-aryl, any of which may replace one or more substituents: halogen, cyano, nitro, -O(C0-4-alkyl), C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CON(C0-4-alkyl)(C0-10-alkyl), -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); and

n2, n3, n4, n5, n6 and n7 each independently is 0, 1 or 2.

In another embodiment of this second aspect of the present compound of the invention of formula I-B:

or its pharmaceutically acceptable salt, in which:

X represents a substituted imidazolyl;

R2and R3each independently represents a C0-10-alkyl, C2-10alkenyl,2-10-quinil,1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl,1-10-alkoxy-C2-10-quinil,1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl,1-10-alkylthio-C2-10-quinil, cyclo-C3-8-alkyl, cyclo-C3-8alkenyl, cyclo-C3-8-alkyl-C1-10-alkyl, cyclo-C3-8alkenyl-C1-10-alkyl, d is CLO-C 3-8-alkyl-C2-10alkenyl, cyclo-C3-8alkenyl-C2-10alkenyl, cyclo-C3-8-alkyl-C2-10-quinil, cyclo-C3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl, heterocyclyl-C2-10-quinil,1-10-alkylsulphonyl,2-10-alkenylboronic,2-10-alkenylboronic,1-10-alkoxycarbonyl,1-10-alkoxycarbonyl-C1-10-alkyl, mono1-6-alkylaminocarbonyl, dis1-6-alkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl or1-10-alkyl(aryl)aminocarbonyl, any of which may replace one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR71R81or-NR71R81; or aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR71With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR71R81, -SO2NR71R81or-NR71R81; or hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10-quinil, any withwhich, may replace one or more independent substituents: halogen, cyano, nitro, -OR71With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR71R81, -SO2NR71R81or-NR71R81;

or R2and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: With1-6-alkyl, halogen, cyano, nitro, -OR71, -SO2NR71R81or-NR71R81;

G1means-OR72, -SR72, -NR72R82(R9)n5or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R 72; or in the case of-NR72R82(R9)n5R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83;

Z means-aryl-, -arylalkyl-, -aryloxy-, -oxyaryl-, -arylalkyl-, -alkynylaryl-, -hetaryl-, -getariako-, -alkylether-, -heterolactic-, -alkenylacyl - or-aryl-, any of which may replace R68;

R4band R5beach independently represents a C0-10-alkyl, C2-10alkenyl,2-10-quinil,1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl,1-10-alkoxy-C2-10-quinil,1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl,1-10-alkylthio-C2-10-quinil, cyclo-C3-8-alkyl, cyclo-C3-8alkenyl, cyclo-C3-8-alkyl-C1-10-alkyl, cyclo-C3-8alkenyl-C1-10-alkyl, cyclo-C3-8-alkyl-C2-10alkenyl, cyclo-C3-8alkenyl-C2-10alkenyl, cyclo-C3-8-alkyl-C2-10-quinil, cyclo-C3-8-alkenyl-C 2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl or heterocyclyl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR77R87, -SO2NR77R87or-NR77R87; or hetaryl-C0-10-alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR77R87, -SO2NR77R87or-NR77R87; or mono(C1-6-alkyl)amino-C1-6-alkyl, di(C1-6-alkyl)amino-C1-6-alkyl, mono(aryl)amino-C 1-6-alkyl, di(aryl)amino-C1-6-alkyl or-N(C1-6-alkyl)-C1-6-alkyl-aryl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR77R87, -SO2NR77R87or-NR77R87; or R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, it called the ring may replace R69;

R67, R68and R69each, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88C0-10-alkyl, C2-10alkenyl, C2-10-quinil, C1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl, C1-10-alkoxy-C2-10-quinil, C 1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl, C1-10-alkylthio-C2-10-quinil, ciclos3-8-alkyl, ciclos3-8alkenyl, ciclos3-8-alkyl-C1-10-alkyl, cyclo-C3-8alkenyl-C1-10-alkyl, ciclos3-8-alkyl-C2-10alkenyl, ciclos3-8alkenyl-C2-10alkenyl, ciclos3-8-alkyl-C2-10-quinil, ciclos3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl or heterocyclyl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR778, -SO2NR778R888or-NR778R888; or aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR778C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR778R888, -SO2NR778R888or-NR778R888; or hetaryl-C0-10-alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, NIT is about, -OR778C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR778R888, -SO2NR778R888or-NR778R888; or mono-(C1-6-alkyl)amino-C1-6-alkyl, di(C1-6-alkyl)amino1-6-alkyl, mono(aryl)amino-C1-6-alkyl, di(aryl)amino-C1-6-alkyl, N(C1-6-alkyl)-C1-6-alkyl-aryl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR778C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR778R888, -SO2NR778R888or-NR778R888; or in the case of-NR78R88(R98)n7R78and R88taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR778R888or-NR778R888;

R7, R71, R72, R3 , R75, R775, R7775, R76, R77, R78, R778, R8, R81, R82, R83, R85, R86, R87, R88, R888, R9, R95and R98each independently represents a C0-10-alkyl, C2-10alkenyl, C2-10-quinil, C1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl, C1-10-alkoxy-C2-10-quinil, C1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl, C1-10-alkylthio-C2-10-quinil, ciclos3-8-alkyl, ciclos3-8alkenyl, ciclos3-8-alkyl-C1-10-alkyl, ciclos3-8alkenyl-C1-10-alkyl, ciclos3-8alkyl-C2-10alkenyl, ciclos3-8alkenyl-C2-10alkenyl, ciclos3-8-alkyl-C2-10-quinil, ciclos3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl, heterocyclyl-C2-10-quinil, C1-10-alkylsulphonyl, C2-10-alkenylboronic, C2-10-alkenylboronic, C1-10-alkoxycarbonyl, C1-10-alkoxycarbonyl-C1-10-alkyl, mono1-6-alkylaminocarbonyl, di-C1-6-alkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl or1-10-alkyl(aryl)aminocarbonyl, any of which may replace one or more independent substituents: halogen, cyano, Hydra is XI, nitro, With1-10-alkoxy, -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -O(C0-4-alkyl), C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CON(C0-4-alkyl)(C0-10-alkyl), -SO2N(C0-4-alkyl)(C0-10-alkyl), or-N(C0-4-alkyl)(C0-4-alkyl); hetaryl-C0-10-alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -O(C0-4-alkyl), C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CON(C0-4-alkyl)(C0-10-alkyl), -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); or mono(C1-6-alkyl)amino-C1-6-alkyl, di(C1-6-alkyl)amino-C1-6-alkyl, mono(aryl)amino-C1-6-alkyl, di(aryl)amino-C1-6-alkyl or N(C1-6-alkyl)-C1-6-alkyl-aryl, uboi of which, may replace one or more substituents: halogen, cyano, nitro, -O(C0-4-alkyl), C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CON(C0-4-alkyl)(C0-10-alkyl), -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); and

n2, n3, n4, n5, n6 and n7 each independently is 0, 1 or 2.

In the third aspect of the present intermediate compound of the invention, which is depicted by formula II;

or its pharmaceutically acceptable salt, in which:

R2and R3each independently represents a C0-10-alkyl, C2-10alkenyl,2-10-quinil,1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl,1-10-alkoxy-C2-10-quinil,1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl,1-10-alkylthio-C2-10-quinil, cyclo-C3-8-alkyl, cyclo-C3-8alkenyl, cyclo-C3-8-alkyl-C1-10-alkyl, cyclo-C3-8alkenyl-C1-10-alkyl, cyclo-C3-8-alkyl-C2-10alkenyl, cyclo-C3-8alkenyl-C2-10alkenyl, cyclo-C3-8-alkyl-C2-10-quinil, cyclo-C3-8alkenyl-C2-10-quinil, the heterocycle is l-C 0-10-alkyl, heterocyclyl-C2-10alkenyl, heterocyclyl-C2-10-quinil,1-10-alkylsulphonyl,2-10-alkenylboronic,2-10-alkenylboronic,1-10-alkoxycarbonyl,1-10-alkoxycarbonyl-C1-10-alkyl, mono1-6-alkylaminocarbonyl, dis1-6-alkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl or1-10-alkyl(aryl)aminocarbonyl, any of which may replace one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR71R81or-NR71R81; or aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR71With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR71R81, -SO2NR71R81or-NR71R81; or heteroaryl-C0-10-alkyl, heteroaryl-C2-10alkenyl or heteroaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR71With1-10-alkyl, C2-10-alkenyl,2-10-alkynyl is, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR71R81, -SO2NR71R81or-NR71R81;

or R2and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: With1-6-alkyl, halogen, cyano, nitro, -OR71, -SO2NR71R81or-NR71R81;

G1means-OR72, -SR72, -NR72R82(R9)n5or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, any of which may replace one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or in the case of-NR72R82(R9)n5R72and R82taken together with the nitrogen atom to which they attached, form a 3-10-membered saturated number of the TSO, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83;

Z means-aryl-, -arylalkyl-, -aryloxy-, -oxyaryl-, -arylalkyl-, -alkynylaryl-, -hetaryl-, -getariako-, -alkylether-, -heterolactic-, -alkenylacyl - or-aryl-, any of which may replace R68;

Q1represents a C0-6-alkyl, -OR75, -NR75R85(R95)n6, -CO2R75, -CONR75R85, -(C=S)OR75, -(C=O)SR75, -NO2, -CN, halogen, -S(O)n6R75, -SO2NR75R85, -NR75(C=NR775)NR7775R85, -NR75(C=NR775OR7775, -NR75(C=NR775)SR7775, -O(C=O)OR75, -O(C=O)NR75R85, -O(C=O)SR75, -S(C=O)OR75, -S(C=O)NR75R85, -S(C=O)SR75, -NR75(C=O)NR775R85or-NR75(C=S)NR775R85; in the case of-NR75R85(R95)n6R75and R85taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, any of which may replace one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR76R86or-NR76R86;

R4band R5beach independently represents a C0-10-alkyl, C2-10alkenyl,2-10-quinil,1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl,1-10-alkoxy-C2-10-quinil,1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl,1-10-alkylthio-C2-10-quinil, cyclo-C3-8-alkyl, cyclo-C3-8alkenyl, cyclo-C3-8-alkyl-C1-10-alkyl, cyclo-C3-8alkenyl-C1-10-alkyl, cyclo-C3-8-alkyl-C2-10alkenyl, cyclo-C3-8alkenyl-C2-10alkenyl, cyclo-C3-8-alkyl-C2-10-quinil, cyclo-C3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl or heterocyclyl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77With1-10-alkyl, C2-10-al is anilam, With2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR77R87, -SO2NR77R87or-NR77R87; or hetaryl-C0-10-alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR77R87, -SO2NR77R87or-NR77R87; or mono(C1-6-alkyl)amino-C1-6-alkyl, di(C1-6-alkyl)amino-C1-6-alkyl, mono(aryl)amino-C1-6-alkyl, di(aryl)amino-C1-6-alkyl or-N(C1-6-alkyl)-C1-6-alkyl-aryl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR77R87, -SO2NR77R87or-NR77R87; or R4bwith R5btaken together with the suitable the carbon atom, to which they attached, form a 3-10-membered saturated or unsaturated ring, any of which may replace R69; or R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, any of which may replace R69;

R7, R71, R72, R73, R75, R775, R7775, R76, R77, R78, R778, R8, R81, R82, R83, R85, R86, R87, R88, R888, R9, R95and R98each independently represents a C0-10-alkyl, C2-10alkenyl, C2-10-quinil, C1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl, C1-10-alkoxy-C2-10-quinil, C1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl, C1-10-alkylthio-C2-10-quinil, ciclos3-8-alkyl, ciclos3-8alkenyl, ciclos3-8-alkyl-C1-10-alkyl, ciclos3-8alkenyl-C1-10-alkyl, ciclos3-8alkyl-C2-10alkenyl, ciclos3-8alkenyl-C2-10alkenyl, ciclos3-8-alkyl-C2-10-quinil, ciclos3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl, heterocyclyl-C2-10-quinil, C1-10-alkyls ronil, C2-10-alkenylboronic, C2-10-alkenylboronic, C1-10-alkoxycarbonyl, C1-10-alkoxycarbonyl-C1-10-alkyl, mono1-6-alkylaminocarbonyl, di-C1-6-alkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl or1-10-alkyl(aryl)aminocarbonyl, any of which may replace one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -O(C0-4-alkyl), C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CON(C0-4-alkyl)(C0-10-alkyl), -SO2N(C0-4-alkyl)(C0-10-alkyl), or-N(C0-4-alkyl)(C0-4-alkyl); hetaryl-C0-10-alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -O(C0-4-alkyl), C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C210 -alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CON(C0-4-alkyl)(C0-10-alkyl), -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); or mono(C1-6-alkyl)amino-C1-6-alkyl, di(C1-6-alkyl)amino-C1-6-alkyl, mono(aryl)amino-C1-6-alkyl, di(aryl)amino-C1-6-alkyl or N(C1-6-alkyl)-C1-6-alkyl-aryl, any of which may replace one or more substituents: halogen, cyano, nitro, -O(C0-4-alkyl), C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CON(C0-4-alkyl)(C0-10-alkyl), -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); and

n1, n2, n3, n4, n5, n6 and n7 each independently is 0, 1 or 2.

In the fourth aspect of the present intermediate compound of this invention of formula III;

or its pharmaceutically acceptable salt, in which:

R2and R3each independently represents a C0-10-alkyl, C2-10alkenyl,2-10-quinil,1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl,1-10-alkoxy-C2-10-quinil,1-10-alkylthio-C1-10alkyl, With1-10-alkylthio-C2-10alkenyl,1-10-alkylthio-C2-10-quinil, cyclo-C3-8-alkyl, cyclo-C3-8alkenyl, cyclo-C3-8-alkyl-C1-10-alkyl, cyclo-C3-8alkenyl-C1-10-alkyl, cyclo-C3-8-alkyl-C2-10alkenyl, cyclo-C3-8alkenyl-C2-10alkenyl, cyclo-C3-8-alkyl-C2-10-quinil, cyclo-C3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl, heterocyclyl-C2-10-quinil,1-10-alkylsulphonyl,2-10-alkenylboronic,2-10-alkenylboronic,1-10-alkoxycarbonyl,1-10-alkoxycarbonyl-C1-10-alkyl, mono1-6-alkylaminocarbonyl, dis1-6-alkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl or1-10-alkyl(aryl)aminocarbonyl, any of which may replace one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR71R81or-NR71R81; or aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR71With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-1 -quinil, -COOH, C1-4-alkoxycarbonyl, -CONR71R81, -SO2NR71R81or-NR71R81; or heteroaryl-C0-10-alkyl, heteroaryl-C2-10alkenyl or heteroaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR71With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR71R81, -SO2NR71R81or-NR71R81;

or R2and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: With1-6-alkyl, halogen, cyano, nitro, -OR71, -SO2NR71R81or-NR71R81;

G1means-OR72, -SR72, -NR72R82(R9)n5or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring, or heterocyclic nenas the seal ring, any of which may replace one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or in the case of-NR72R82(R9)n5R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83;

Z means-aryl-, -arylalkyl-, -aryloxy-, -oxyaryl-, -arylalkyl-, -alkynylaryl-, -hetaryl-, -getariako-, -alkylether-, -heterolactic-, -alkenylacyl - or-aryl-, any of which may replace R68;

Q1represents a C0-6-alkyl, -OR75, -NR75R85(R95)n6, -CO2R75, -CONR75R85, -(C=S)OR75, -(C=O)SR75, -NO2, -CN, halogen, -S(O)n6R75, -SO2NR75R85, -NR75(C=NR775)NR7775R85, -NR75(C=NR775OR7775, -NR75(C=NR775)SR7775, -O(C=O)OR75, -O(C=O)NR75R85, -O(C=O)SR75, -S(C=O)OR75, -S(=O)NR 75R85, -S(C=O)SR75, -NR75(C=O)NR775R85or-NR75(C=S)NR775R85; in the case of-NR75R85(R95)n6R75and R85taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, any of which may replace one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR76R86or-NR76R86;

R4band R5beach independently represents a C0-10-alkyl, C2-10alkenyl,2-10-quinil,1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl,1-10-alkoxy-C2-10-quinil,1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl,1-10-alkylthio-C2-10-quinil, cyclo-C3-8-alkyl, cyclo-C3-8alkenyl, cyclo-C3-8-alkyl-C1-10-alkyl, cyclo-C3-8alkenyl-C1-10-alkyl, cyclo-C3-8-alkyl-C2-10alkenyl, cyclo-C3-8alkenyl-C2-10alkenyl, cyclo-C3-8-alkyl-C2-10-quinil, cyclo-C3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl or heterocyclyl-C2-10-quinil, lubies which, may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR77R87, -SO2NR77R87or-NR77R87; or hetaryl-C0-10-alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR77R87, -SO2NR77R87or-NR77R87; or mono(C1-6-alkyl)amino-C1-6-alkyl, di(C1-6-alkyl)amino-C1-6-alkyl, mono(aryl)amino-C1-6-alkyl, di(aryl)amino-C1-6-alkyl or-N(C1-6-alkyl)-C1-6-alkyl-aryl, any of which may replace one or the more independent substituents: halogen, cyano, nitro, -OR77With1-10-alkyl, C2-10-alkenyl,2-10-quinil, halogen-C1-10-alkyl, halogen-C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR77R87, -SO2NR77R87or-NR77R87; or R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, any of which may replace R69; or R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, any of which may replace R69;

R67, R68and R69represent halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88C0-10-alkyl, C2-10alkenyl, C2-10-quinil, C1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl, C1-10-alkoxy-C2-10-quinil, C1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl, C1-10-alkylthio-C2-10-quinil, ciclos3-8-alkyl, ciclos3-8alkenyl, ciclos3-8-alkyl-C1-10-alkyl, cyclo-C3-8-Ala the Nile-C 1-10-alkyl, ciclos3-8-alkyl-C2-10alkenyl, ciclos3-8alkenyl-C2-10alkenyl, ciclos3-8-alkyl-C2-10-quinil, ciclos3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl or heterocyclyl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR778, -SO2NR778R888or-NR778R888; or aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR778C1-10-alkyl, C2-10alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR778R888, -SO2NR778R888or-NR778R888; or hetaryl-C0-10-alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR778C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR778R888, -SO NR778R888or-NR778R888; or mono-(C1-6-alkyl)amino-C1-6-alkyl, di(C1-6-alkyl)amino-C1-6-alkyl, mono(aryl)amino-C1-6-alkyl, di(aryl)amino-C1-6-alkyl, N(C1-6-alkyl)-C1-6-alkyl-aryl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR778C1-10-alkyl, C2-10-alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CONR778R888, -SO2NR778R888or-NR778R888; or in the case of-NR78R88(R98)n7R78and R88taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR778R888or-NR778R888;

R7, R71, R72, R73, R74, R75, R775, R7775, R76, R77, R78, R778, R8, R81, R82, R83, R85, R86, R87, R88, R888, R9, R95and R9 each independently represents a C0-10-alkyl, C2-10alkenyl, C2-10-quinil, C1-10-alkoxy-C1-10-alkyl, C1-10-alkoxy-C2-10alkenyl, C1-10-alkoxy-C2-10-quinil, C1-10-alkylthio-C1-10-alkyl, C1-10-alkylthio-C2-10alkenyl, C1-10-alkylthio-C2-10-quinil, ciclos3-8-alkyl, ciclos3-8alkenyl, ciclos3-8-alkyl-C1-10-alkyl, ciclos3-8alkenyl-C1-10-alkyl, ciclos3-8-alkyl-C2-10alkenyl, ciclos3-8alkenyl-C2-10alkenyl, ciclos3-8-alkyl-C2-10-quinil, ciclos3-8alkenyl-C2-10-quinil, heterocyclyl-C0-10-alkyl, heterocyclyl-C2-10alkenyl, heterocyclyl-C2-10-quinil,1-10-alkylsulphonyl, C2-10-alkenylboronic, C2-10-alkenylboronic,1-10-alkoxycarbonyl,1-10-alkoxycarbonyl1-10-alkyl, mono1-6-alkylaminocarbonyl, dis1-6-alkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl or1-10-alkyl(aryl)aminocarbonyl, any of which may replace one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); aryl-C0-10-alkyl, aryl-C2-10alkenyl or aryl-C2-10-quinil, l is the fight of which, may replace one or more independent substituents: halogen, cyano, nitro, -O(C0-4-alkyl), C1-10-alkyl, C2-10alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CON(C0-4-alkyl)(C0-4-alkyl), -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); or hetaryl-C0-10-alkyl, hetaryl-C2-10alkenyl or hetaryl-C2-10-quinil, any of which may replace one or more independent substituents: halogen, cyano, nitro, -O(C0-4-alkyl), C1-10-alkyl, C2-10alkenyl, C2-10-quinil, halogen-C1-10-alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CON(C0-4-alkyl)(C0-4-alkyl), -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); or a mono-(C1-6-alkyl)amino-C1-6-alkyl, di(C1-6-alkyl)amino-C1-6-alkyl, mono(aryl)amino-C1-6-alkyl, di(aryl)amino-C1-6-alkyl or N(C1-6-alkyl)-C1-6-alkyl-aryl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -O(C0-4-alkyl), C1-10-alkyl, C2-10alkenyl, C2-10-quinil, halogen-C1-10 -alkyl, halogen-(C2-10-alkenyl, halogen-C2-10-quinil, -COOH, C1-4-alkoxycarbonyl, -CON(C0-4-alkyl)(C0-4-alkyl), -SO2N(C0-4-alkyl)(C0-4-alkyl) or-N(C0-4-alkyl)(C0-4-alkyl); and

n2, n3, n4, n5, n6 and n7 each independently is 0, 1 or 2.

The compounds of this invention include compounds represented by formula I above, or their pharmaceutically suitable salts, and

1) in which X is hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; or

2) in which X represents imidazolyl or triazolyl; or

3) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66and Q1means CO2H or-CO2R75; or

4) in which Y represents oxygen; or

5) in which Y represents oxygen, and X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; or

6) in which Y represents oxygen, and X represents imidazolyl or triazolyl; or

7) in which Y represents oxygen, and X represents imidazolyl or triazolyl, and Q1means CO2H or-CO2R75;or

8) in which Y represents oxygen, and R4aand R5aeach represents hydrogen; or

9) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1, R2and R3each independently represents a C0-10alkyl; G1means-NR72R82or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, it called the ring, possibly substituted by one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, it called the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1represents a C0-6/sub> -alkyl, -CO2R75or-CONR75R85; R4a, R4b, R5aand R5beach, independently means0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6awith R6beach, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; or

10) in which X represents imidazolyl or triazolyl; R1means hydrogen, R2and R3each independently represents a C0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which the WMD appending, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more substituents R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C0-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means CO2R75or-CONR75R85; R4a, R4b, R5aand R5beach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated who also, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, it called the ring may replace R69; and R6aand R6beach represents hydrogen; or

11) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1, R2and R3each independently represents a C0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring, or heterocyclic the case of unsaturated ring, it called the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1represents a C0-6-alkyl, -CO2R75or-CONR75R85; R4aand R5aeach means hydrogen; R4band R5beach, independently means0-10-alkyl, any of which may replace R69; or R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; or

12) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more substituents R66; R1, R2and R3each independently represents a C0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, not asimenia ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more substituents R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means C0-6-alkyl, -CO2R75or-CONR75R85; R4band R5beach independently represents a C0-6-alkyl, or R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10 membered saturated ring; R4aand R5aeach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5a taken together with the respective carbon atom to which they attached, form a 3-10 membered saturated or unsaturated ring, it called the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; or

13) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1, R2and R3each independently represents a C0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more substituents R67and the N heteroatom of Goethe is utilizacao saturated ring or heterocyclic unsaturated ring, perhaps replace the substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means C0-6-alkyl, -CO2R75or-CONR75R85; R4aand R5aeach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5ataken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; and R4bwith R5btaken instead of the e with the respective carbon atom, to which they attach, form a ring cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; or

14) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1, R2and R3each independently represents a C0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more substituents R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means C0-6 -alkyl, -CO2R75or-CONR75R85; R4aand R5aeach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5awhile these ring may replace R69; or R4awith R5ataken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach independently represents-OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; and R4bwith R5bboth represent ethyl or both represent methyl or independently denote ethyl or methyl; or

15) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1, R2and R3each. independently represents a C0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom, to which they attach, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more substituents R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; R4a, R4b, R5aand R5beach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; what if R 4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; and Q1means CO2R75; or

16) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1, R2and R3each independently represents a C0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more substituents R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken instead of the e with the nitrogen atom, to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; R4a, R4b, R5aand R5beach independently represents a C0-6-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; and Q1means CO2H; or

17) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1, R2and R3each independently represents a C0-10-alkyl; Y represents oxygen, Q1represents a C0-6-alkyl, -CO2R75or-CON75R85; R4a, R4bR5aand R5beach, independently means0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently represents halogen, -OR78, -NR78R88(R 98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; and G1means di(C1-6-alkyl)amino; or

18) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1, R2and R3each independently represents a C0-10-alkyl; Y represents oxygen, Q1represents a C0-6-alkyl, -CO2R75or-CON75R85; R4a, R4bR5aand R5beach, independently means0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6b each, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; and G1means dimethylamino, ethylmethylamino, diethylamino or isopropylethylene; or

19) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1represents a C0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or bol is e independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means C0-6-alkyl, -CO2R75or-CONR75R85; R4a, R4b, R5aand R5beach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; and R2and R3each independently represents hydrogen, methyl or ethyl; or

20) in which X isone hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1and R3each independently represents a C0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more substituents R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means C0-6-alkyl, -CO2R75or-CONR75R85; R4a, R4b, R5aand R5beach independently represents a C0-10-alkyl, any of which is s, may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently represents halogen OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; and R2means hydrogen; and G1and R3taken together with the carbon atom to which they attach, formin which • denotes the carbon to which they attach;

or G1and R3taken together with the carbon atom to which they attach, formin which • denotes the carbon to which they attach, any of which may sameday-10 independent substituents R 67; or

21) in which X represents an imidazole; or

22) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1represents a C0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more substituents R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means C0-6-alkyl, -CO2R75or-CONR75R85; R4a, R4b, R5aand R 5beach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; and R2means hydrogen and R3means methyl; or

23) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1represents a C0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the volume of carbon to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more substituents R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means C0-6-alkyl, -CO2R75or-CONR75R85; R4a, R4b, R5aand R5beach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attach, the image of the Ute 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; and R2means hydrogen and R3means ethyl; or

24) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1represents a C0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring may replace will replace the LEM R 72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means C0-6-alkyl, -CO2R75or-CONR75R85; R4a, R4b, R5aand R5beach independently represents a C0-6-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach n is dependent represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; and R2means hydrogen and R3both denote methyl; or

25) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1and R3each independently represents a C0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, NITR is, With1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means C0-6-alkyl, -CO2R75or-CONR75R85; R4a, R4b, R5aand R5beach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; R2means hydrogen, and G1and R3taken together with the carbon atom to which they attach, formG1and R3taken together with the carbon atom to which they attach, formin which • denotes the carbon to which they attach, any of which may replace 1-10 independent substituents R67; and n2, n3 and n4, each equal to 1, and Z signifies aryl; or

26) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1and R3each independently represents a C0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring, or heterocyclic of nenasi the military ring and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means C0-6-alkyl, -CO2R75or-CONR75R85; R4a, R4b, R5aand R5beach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; R2means in dorog, and G1and R3taken together with the carbon atom to which they attach, formin which • denotes the carbon to which they attach, or

G1and R3taken together with the carbon atom to which they attach, formin which • denotes the carbon to which they attach, any of which may replace 1-10 independent substituents R67; and n2 is 1; n3 and n4 each equal to 0; and Z denotes aryl; or

27) in which Z represents aryl or aryloxy or oxyaryl; or

28) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1and R3each independently represents a C0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72 and R 82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means CO2R75; R4a, R4b, R5aand R5beach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently represents halogen, -OR78, -NR78R88/sup> (R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; R2means hydrogen, and G1and R3taken together with the carbon atom to which they attach, formin which • denotes the carbon to which they attach, or

G1and R3taken together with the carbon atom to which they attach, formin which • denotes the carbon to which they attach, any of which may replace 1-10 independent substituents R67; and n2, n3 and n4 each, is equal to 1; and Z denotes aryl; and n3 is 0; or

29) in which X represents a hetaryl, imidazolyl or triazolyl, any of which may replace one or more independent substituents R66; R1and R3each independently represents a C0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent R67and the N heteroatom of the heterocyclic saturated ring is whether heterocyclic unsaturated ring, perhaps replace the substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means CO2H; R4a, R4b, R5aand R5beach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently p is ecstasy a halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; R2means hydrogen, and G1and R3taken together with the carbon atom to which they attach, formin which • denotes the carbon to which they attach, or

G1and R3taken together with the carbon atom to which they attach, formin which • denotes the carbon to which they attach, any of which may replace 1-10 independent substituents R67; and n2, n3 and n4 each, is equal to 1; and Z denotes aryl; and n3 is 0; or

30) in which X represents imidazolyl or triazolyl; R1means hydrogen; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken the together with the nitrogen atom, to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means CO2R75or-CONR75R85; R4a, R4b, R5aand R5beach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach independently represents hydrogen; R2means hydrogen, and R3who appoints methyl; or

31) in which X represents imidazolyl or triazolyl; R1means hydrogen; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means CO2R75or-CONR75R85; R4a, R4b, R5aand R5beach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR 77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach represents hydrogen; R2means hydrogen, and R3means ethyl; or

32) in which X represents imidazolyl or triazolyl; R1means hydrogen; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attach, brisout 3-10-membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means CO2R75or-CONR75R85; R4a, R4b, R5aand R5beach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, it called the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach represents hydrogen; R2and R3means methyl; or

33) in which X represents a hetaryl, imidazolyl or triazolyl; Liu the nd of which, may replace one or more independent substituents R66; R1and R3each, independently means0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring may replace R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means0-6-alkyl, -CO2R75or-CONR75R85; R4a, R4b, R5aand R5beach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: what alogena, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; R2means hydrogen, and G1and R3taken together with the carbon atom to which they attach, formin which • denotes the carbon to which they attach, or

G1and R3taken together with the carbon atom to which they attach, formin which • denotes the carbon to which they attach, any of which may replace 1-10 independent substituents R67; and n1 and n2 each is equal to 1; and Z means the AET aryl; or

34) in which X represents a hetaryl, imidazolyl or triazolyl; any of which may replace one or more independent substituents R66; R1and R3each, independently means0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; Q1means C0-6-alkyl, -CO2R75or-CONR75R85; R4a, R4b, R5aand R5beach independently represents the t With a 0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; R2means hydrogen, and G1and R3taken together with the carbon atom to which they attach, formin which • denotes the carbon to which they attach, or

G1and R3taken together with the carbon atom to which they attach, formin which • denotes the carbon to which they attach, and any who are, perhaps replace 1-10 independent substituents R67; n1 and n2 each represent 1; n3 and n4, each corresponding to 0; and Z signifies aryl; or

35) in which X represents a hetaryl, imidazolyl or triazolyl; any of which may replace one or more independent substituents R66; R1and R3each, independently means0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83or-NR73R83; Y represents oxygen; R4a, R4b , R5aand R5beach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; R2means hydrogen, and G1and R3taken together with the carbon atom to which they attach, formin which • denotes the carbon to which they attach, or

G1and R3taken together with the carbon atom to which they attach, formthat is where the • denotes the carbon to which they attach, any of which may replace 1-10 independent substituents R67; n1 and n2 each represent 1; and Z signifies aryl; Q1represents-CO2R75; or

36) in which X represents a hetaryl, imidazolyl or triazolyl; any of which may replace one or more independent substituents R66; R1and R3each, independently means0-10-alkyl; G1means-NR72R82; or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent R67and the N heteroatom of the heterocyclic saturated ring or heterocyclic unsaturated ring, possibly substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring or heterocyclic unsaturated ring, and named the ring, possibly substituted by one or more independent substituents: halogen, cyano, hydroxy, nitro, C1-10-alkoxy, -SO2NR73R83 73R83; Y represents oxygen; R4a, R4b, R5aand R5beach independently represents a C0-10-alkyl, any of which may replace one or more independent substituents: halogen, cyano, nitro, -OR77, -SO2NR77R87or-NR77R87; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated ring, and named the ring may replace R69; or R4awith R5aor R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10-membered saturated or unsaturated heterocyclic ring, and named the ring may replace R69; and R6aand R6beach, independently represents halogen, -OR78, -NR78R88(R98)n7, -CO2R78, -CONR78R88, -NO2, -CN, -S(O)n7R78, -SO2NR78R88or0-10-alkyl; R2means hydrogen, and G1and R3taken together with the carbon atom to which they attach, formin which • denotes the carbon to which they attach, or

G1and R3taken together with the carbon atom to which is attached, formin which • denotes the carbon to which they attach, any of which may replace 1-10 independent substituents R67; n1 and n2 each represent 1; and Z signifies aryl; Q1represents-CO2H;

and in which in each case other variables are as described above for formula I.

The compounds of this invention include:

3-[6-(2-Dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxy]-2,2-dimethyl-propionic acid;

2-[6-(2-Dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-2-ethyl-butyric acid;

1-[6-(2-Dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-cyclopropane-carboxylic acid;

1-[6-(2-Dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-CYCLOBUTANE-carboxylic acid;

1-[6-(2-Dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-cyclopentane-carboxylic acid;

1-[6-(2-Dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-cyclohexane-carboxylic acid;

1-{6-[1-Imidazol-1-yl-2-(isopropylethylene)-propyl]-naphthalene-2-yl-oxymethyl}-cyclopentane-carboxylic acid;

3-[6-(2-Diethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxy]-2,2-dimethyl-propionic acid;

3-{6-[1-Imidazol-1-yl-2-(isopropylethylene)-propyl]-naphthalene-2-yl-oxy}-2,2-dimethyl-propionic acid

3-{6-[2-(Ethyl-methyl-amino)-1-imidazol-1-yl-propyl]-naphthalene-2-yl-oxy}-2,2-dimethyl-propionic acid;

3-[6-(2-Dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxy]-2,2-dimethyl-propionamide;

3-[6-(2-Dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxy]-2,2,N-trimethyl-propionamide;

3-[6-(2-Dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxy]-2,2,N,N-tetramethyl-propionamide;

3-[6-(2-Dimethylamino-1-imidazol-1-yl-butyl)-naphthalene-2-yl-oxy]-2,2-dimethyl-propionic acid;

4-[6-(2-Dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-benzoic acid;

3-[6-(2-Dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-benzoic acid;

4-[6-(2-Dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-benzamide;

4-[6-(2-Dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-N-methyl-benzamide;

4-[6-(2-Dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-N,N-dimethyl-benzamide; and

1-[(6-Benzyloxy-naphthalene-2-yl)-(1-methyl-pyrrolidin-2-yl)-methyl]-1H-imidazole.

Unless otherwise noted, the relationship of the fragments of the names of the connections carried out on the most right of the referenced fragment. That is the name of the Deputy begins with the end of the fragment continues any bridge fragments and connecting ends of the fragment. For example, getarity-C1-4-alkyl is a hetaryl group, joined the via thio-sulfur K 1-4-alkyl, which is attached to the chemical elements supporting the Deputy.

Used, for example, in the description, the term "C0-4-alkyl" means alkyl, containing 0-4 carbon, that is, 0, 1, 2, 3 or 4 carbon straight or branched configuration. Alkyl containing no carbon is hydrogen, when the alkyl is a limit group. Alkyl containing no carbon is a direct link, if the alkyl represents a bridging group.

In all embodiments of this invention the term "alkyl" includes an alkyl group as branched and straight chain. Typical alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, n-heptyl, isooctyl, nonyl, decyl, undecyl, dodecyl, tetradecyl, hexadecyl, octadecyl, eicosyl and the like.

The term "halogen" refers to fluorine, chlorine, bromine or iodine.

The term "halogenated" refers to the group of alkyl, substituted by one or more of the groups halogen, such as chloromethyl, 2-bromacil, 3-improper, trifluoromethyl, performaer, 8-chloranil and the like.

The term "cycloalkyl" refers to a cyclic aliphatic ring structure, possibly substituted by alkyl, hydroxy and halogen, such as cyclopropyl, metalcolor the saws, cyclobutyl, cyclopentyl, 2-hydroxycyclopent, cyclohexyl, 4-chlorcycloguanil, cycloheptyl, cyclooctyl and the like.

The term "alkylcarboxylic" refers to a fragment of ester, for example acetoxymethyl, n-butyryloxy and the like.

The term "alkenylboronic" implies alchemilleta functionality, such as propenyl and the like.

The term "hydroxyalkyl" refers to the group of alkyl, substituted by one or more hydroxy groups, such as hydroxymethyl, 2,3-dihydroxybutyl and the like.

The term "alkylsulfonyl" refers to the group of alkyl, substituted fragment alkylsulfonyl, such as methylethyl, isopropylacetanilide and the like.

The term "alkylsulfonyl" refers to a fragment of sulfonyl, substituted alkyl group, for example, mesyl, n-propylsulfonyl and the like.

The term "acetylaminophenol" refers to the group of alkyl, substituted amide fragment, such as acetamidomethyl and the like.

The term "acetylaminophenol" refers to the group alkenyl, substituted amide fragment, for example 2-(acetylamino)vinyl and the like.

The term "alkenyl" refers to "atilano" unsaturated hydrocarbon group, straight or branched chain containing 1 or 2 ethylene communication, for example vinyl, allyl, 1-butenyl, 2-bout the sludge, Isopropenyl, 2-pentenyl and the like.

The term "halogenoalkanes" refers to the group alkenyl substituted by one or more groups of halogen.

The term "cycloalkenyl" refers to a cyclic aliphatic ring structure, possibly substituted by alkyl, hydroxy and halogen, having 1 or 2 ethylene communication, such as methylcyclopropyl, triftormetilfullerenov, cyclopentenyl, cyclohexenyl, 1,4-cyclohexadienyl and the like.

The term "quinil" refers to an unsaturated hydrocarbon group, straight or branched chain having 1 or 2 acetylene communication, such as ethinyl, propargyl and the like.

The term "halogenoalkanes" refers to the group of quinil substituted by one or more groups of halogen.

The term "alkylaryl" has to do with alkylate functionality, for example, acetyl, n-butyryl and the like.

The term "alkenylboronic" has to do with altercate functionality, such as propanol and the like.

The term "aryl" refers to phenyl or naphthyl, which, it may be possible to replace. Typical akrilovye deputies, without limitation, include phenyl, 4-chlorophenyl, 4-forfinal, 4-bromophenyl, 3-nitrophenyl, 2-methoxyphenyl, 2-were, 3-were, 4-were, 4-ethylphenyl, 2-methyl-3-methoxyphenyl, 2,4-dibromophenyl, 3,5-deltorphin is l, 3, 5dimethylphenyl, 2,4,6-trichlorophenyl, 4-methoxyphenyl, naphthyl, 2-chloronaphthyl, 2,4-acid, 4-(trifluoromethyl)phenyl and 2-iodine-4-were.

[164] the Terms "heteroaryl" or "hetaryl" relate to a substituted or unsubstituted 3-10-membered unsaturated ring containing one, two, three or four heteroatoms, preferably one or two heteroatoms independently selected from oxygen, nitrogen and sulfur or to a bicyclic unsaturated ring system containing up to 10 atoms including at least one heteroatom selected from oxygen, nitrogen and sulfur. Examples of getarrow not limited to, include 2-, 3 - or 4-pyridinyl, pyrazinyl, 2-, 4 - or 5-pyrimidinyl, pyridazinyl, triazolyl, tetrazolyl, imidazolyl, 2 - or 3-thienyl, 2 - or 3-furyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolin, oxadiazolyl, thiadiazolyl, hinely, ethanolic, benzimidazolyl, benzotriazolyl, benzofuranyl and sensational. Heterocyclic ring may be substituted by a maximum of two deputies.

The terms "aryl-alkyl" or "arylalkyl" is used to describe the group in which the chain of the alkyl may be branched or straight chain with a part of the above-described aryl, forming a bridging portion of the fragment aryl-alkyl. Examples of the groups aryl-alkyl, without limitation, may include, substituted benzyl, f is Neil, inproper and terbutyl, such as 4-Chlorobenzyl, 2,4-dibromobenzyl, 2-methylbenzyl, 2-(3-forfinal)ethyl, 2-(4-were)ethyl, 2-(4-(trifluoromethyl)phenyl)ethyl, 2-(2-methoxyphenyl)ethyl, 2-(3-nitrophenyl)ethyl, 2-(2,4-dichlorophenyl)ethyl, 2-(3,5-acid)ethyl, 3-phenylpropyl, 3-(3-chlorophenyl)propyl, 3-(2-were)propyl, 3-(4-methoxyphenyl)propyl, 3-(4-trifluoromethyl)phenyl)propyl, 3-(2,4-dichlorophenyl)propyl, 4-phenylbutyl, 4-(4-chlorophenyl)butyl, 4-(2-were)butyl, 4-(2,4-dichlorophenyl)butyl, 4-(2-methoxyphenyl)butyl and 10-phenyldeca.

The terms "aryl-cycloalkyl" or "aristically" is used to describe the group in which the aryl group attached to the group cycloalkyl, for example vinylcyclopentane and the like.

The terms "aryl-alkenyl" or "arylalkyl" is used to describe the group in which the chain alkenyl may be branched or straight chain with a part of the aryl described above, forming a bridging portion of the fragment arylalkyl, such as styryl (2-phenylphenyl), fenpropidin and the like.

The terms "aryl-quinil" or "arylalkyl" is used to denote a group in which the chain quinil may be branched or straight chain with a part of the aryl described above, forming a bridging portion of the fragment aryl-quinil, for example 3-phenyl-1-PROPYNYL and the like.

The terms "aryl-oxy" or "aryloxy" is used to denote the con is ewww the group of aryl, attached to the bridging atom of oxygen. Typical of the groups aryl-hydroxy include phenoxy, 3,4-dichlorophenoxy and the like.

The terms "aryl-oxyalkyl" or "aryloxyalkyl" is used to indicate the group in which the alkyl group substituted by the group aryl-oxy, such as pentafluorophenoxyacetyl and the like.

The term "hetaryl-hydroxy"or "heteroaryl-hydroxy"or "retailexe", or "heteroaromatic" is used to describe the end hetaryl group attached to the bridge to the oxygen atom. Typical group hetaryl-hydroxy include 4,6-dimethoxypyrimidine-2-yl-oxy and the like.

The terms "getarray", or heteroaromatic", or hetaryl-alkyl", or heteroaryl-alkyl" is used to describe groups to which the chain of the alkyl may be branched or straight chain with the part of heteroaryl described above, forming a bridging portion of the movie heteroalkyl, for example, 3-furylmethyl, Tennille, furfuryl and the like.

The terms "heterolactic", or "heteroaromatic"or "hetaryl-alkenyl", or "heteroaryl-alkenyl" is used to indicate the group in which the chain alkenyl may be branched or straight chain with the part above heteroaryl, forming a bridging portion of the fragment heteroalkyl, for example 3-(4-pyridyl)-1-propenyl.

The terms "hetarylethenyl", Il is "heteroarylboronic", or "hetaryl-quinil", or "heteroaryl-quinil belong to the group in which the chain quinil may be branched or straight chain with a part of heteroaryl described above, forming a bridging portion of the movie heteroalkyl, for example 4-(2-thienyl)-1-butynyl.

The term "heterocyclyl" refers to a substituted or unsubstituted 3-10 membered saturated ring containing one, two or three heteroatoms, preferably one or two heteroatoms independently selected from oxygen, nitrogen and sulfur or to a bicyclic ring system containing up to 10 atoms including at least one heteroatom selected from oxygen, nitrogen and sulfur, where the ring containing the heteroatom is saturated. Examples including heterocyclyl not limited to, include tetrahydrofuran, tetrahydrofuryl, pyrrolidinyl, piperidinyl, 4-pyranyl, tetrahydropyranyl, tylenol, morpholinyl, piperazinil, DIOXOLANYL, dioxane, indolinyl and 5-methyl-6-chromanol.

The terms "geterotsiklicheskikh" or heterocyclyl-alkyl" are relevant to the group in which the chain of the alkyl may be branched or straight chain with the part heterocyclyl described above, forming a bridging portion of the movie geterotsiklicheskikh, for example 3-piperidinylmethyl and the like.

The terms "heterocyclisation or GE is eroticly-alkenyl" is used to describe the group, in which the chain alkenyl may be branched or straight chain with the part heterocyclyl described above, forming a bridging portion of the fragment geterotsiklicheskikh, for example 2-morpholinyl-1-propenyl.

The terms "geterotsiklicheskikh" or heterocyclyl-quinil" is used to describe groups to which the chain quinil may be branched or straight chain with the part heterocyclyl described above, forming a bridging portion of the movie geterotsiklicheskikh, for example 2-pyrrolidinyl-1-butynyl.

The term "carboxylate" includes the above-described alkyl group as branched and straight chain attached to the carboxyl (-COOH) group.

The term "carboxylphenyl" includes the above-described group alkenyl both branched and straight chain attached to the carboxyl (-COOH) group.

The term "carboxylating" includes groups described above quinil both branched and straight chain attached to the carboxyl (-COOH) group.

The term "carboxylicacid" refers to a carboxyl (-COOH) group attached to tsiklicheskii aliphatic ring structure, which is describe above.

The term "carboxylicacid" refers to a carboxyl (-COOH) group attached to a cyclic aliphatic ring p is the established levels, having 1 or 2 ethylene, which is describe above.

The terms "cycloalkenyl" or "cycloalkyl-alkyl" are related to the above-mentioned group of cycloalkyl attached to the alkyl group, such as cyclopropylmethyl, cyclohexylethyl and the like.

The terms "cycloalkenyl" or "cycloalkyl-alkenyl" are relevant to the group cycloalkyl that describe above, attached to alkenyl, such as cyclohexylphenol, cycloheptylmethyl and the like.

The terms "cycloalkenyl" or "cycloalkyl-quinil" relate to the above-mentioned group of cycloalkyl connected to a group of quinil, for example cyclopropylmethyl, 4-cyclopentyl-2-butynyl and the like.

The terms "cycloalkenyl" or cycloalkenyl-alkyl" related to the above group cycloalkenyl attached to the alkyl group, such as 2-(cyclopenten-1-yl)ethyl and the like.

The terms "cycloalkylcarbonyl" or "cycloalkenyl-alkenyl" belong to the above group cycloalkenyl attached to alkenyl, for example 1-(cyclohexen-3-yl)allyl and the like.

The terms "cycloalkenyl" or "cycloalkenyl-quinil" belong to the above group cycloalkenyl connected to a group of quinil, for example 1-(cyclohexen-3-yl)propargyl and the like.

Those who min "carboxycellulose" refers to a carboxyl (-COOH) group, attached to cycloalkyl annular part of the group cycloalkenyl described above.

The term "carboxycellulose" refers to a carboxyl (-COOH) group attached to cycloalkyl annular part of the group cycloalkylcarbonyl described above.

The term "carboxymethyloxysuccinic" refers to a carboxyl (-COOH) group attached to cycloalkyl annular part of the group cycloalkylcarbonyl described above.

The term "carboxylesterases" refers to a carboxyl (-COOH) group attached to cycloalkenyl annular part of the group cycloalkenyl described above.

The term "carboxylmethylenphenylalkyl" refers to a carboxyl (-COOH) group attached to cycloalkenyl annular part of the group cycloalkylcarbonyl described above.

The term "carboxylcontaining" refers to a carboxyl (-COOH) group attached to cycloalkenyl annular part of the group cycloalkylcarbonyl described above.

The term "alkoxy" includes end groups of alkyl with both branched and straight chain attached to the bridging atom of oxygen. Typical alkoxygroup include methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy and the like.

The term "halogenoalkane" refers to the group of alkoxy, for esenkoy one or more of the groups halogen, for example, chloromethoxy, triptoreline, deformedarse, perversonality and the like.

The term "alkoxyalkyl" refers to the group of alkyl, substituted fragment alkoxy, which in turn replaced the second fragment alkoxy, such as methoxyethoxymethyl, isopropoxycarbonyl and the like.

The term "alkylthio" includes groups as alkyl branched and straight chain attached to the bridging atom of sulfur, for example methylthio.

The term "allogenicity" refers to a group of alkylthio, substituted by one or more of the groups halogen, for example, triptoreline.

The term "alkoxyalkyl" refers to the group of alkyl, substituted alkoxy group, for example isopropoxyphenyl.

The term "alkoxyalkyl" refers to the group alkenyl, substituted alkoxy group, for example 3-methoxyethyl.

The term "alkoxyalkyl" refers to a group of quinil, substituted alkoxy group, for example 3-methoxypropyl.

The term "alkoxycarbonyl" refers to alkyl straight or branched chain, substituted by alkoxycarbonyl, such as ethoxycarbonylmethyl, 2-(methoxycarbonyl)propyl, and the like.

The term "alkoxycarbonylmethyl" relates to the above-described alkenyl straight or branched chain, substituted by alkoxycarbonyl, for example 4-(taxicab who yl)-2-butenyl and the like.

The term "alkoxycarbonyl" has to consider the above quinil straight or branched chain, substituted by alkoxycarbonyl, for example 4-(etoxycarbonyl)-2-butynyl and the like.

The term "halogenoacetyl" refers to the above-described alkyl straight or branched chain, substituted, halogenoalkane, for example 2-chloridometer, trifloromethyl and the like.

The term "halogenoacetyl" refers to the above-described alkenyl straight or branched chain, substituted, halogenoalkane, for example 4-(chloromethoxy)-2-butenyl and the like.

The term "halogenoalkanes" refers to the above quinil straight or branched chain, substituted, halogenoalkane, for example 4-(2-floratone)-2-butynyl and the like.

The term "alkylthiomethyl" refers to the above-described alkyl straight or branched chain, substituted by a group of alkylthio, such as methylthiomethyl, 3-(isobutyric)heptyl and the like.

The term "alkylthiophenes" refers to the above-described alkenyl straight or branched chain, substituted by a group of alkylthio, for example 4-(methylthio)-2-butenyl and the like.

The term "alkylthiophenes" refers to the above quinil substituted by a group of alkylthio, for example 4-(ethylthio)-2-butynyl and the like.

The term "halo is talkietoaster" refers to the above-described alkyl straight or branched chain, substituted by a group of allogenicity, for example 2-chloroethylthiomethyl, triptoreline and the like.

The term "halogenoalkanes" refers to the above-described alkenyl straight or branched chain, substituted by a group of allogenicity, for example 4-(chlorotri)-2-butenyl and the like.

The term "halogenoalkanes" refers to the above quinil straight or branched chain, substituted by a group of allogenicity, for example 4-(2-foretelling)-2-butynyl and the like.

The term "dialkoxybenzene" refers to the above-described two alkoxygroup straight or branched chain attached to the pentavalent phosphorus atom containing oxo-Deputy, which in turn is attached to the alkyl, such as diethoxyphosphoryl.

The term "oligomer" refers to low molecular weight polymer, the average molecular weight which is generally about less than 5000 g/mol and degree of polymerization (average number of Monomeric units in the chain) is greater than one, and typically is approximately equal to or less than 50.

Compounds present in the description, contain one or more asymmetric centers and thus can lead to diastereomers and optical isomers. The invention includes all such possible is diastereomer, as well as their racemic mixtures, their essentially pure, separated enantiomers, all possible geometric isomers and their pharmaceutically suitable salts. The above-mentioned formula I is represented without a definitive stereochemistry at certain positions. This invention includes all stereoisomers of the formula I and their pharmaceutically suitable salts. In addition, the invention also includes mixtures of stereoisomers, as well as a dedicated stereoisomers. In the course of the synthesis procedures used to obtain these compounds, or by using methods racemization or epimerization, well-known experts in this field, the products obtained as a result of such methods, may be a mixture of stereoisomers.

Among enantiomers of the compounds as SYN-and anti-isomers, which includes X - and G1Deputy demonstrate the activity. It is established that the SYN-isomer is more active than the anti-isomer and, thus, is the preferred isomer. In addition, it appears preferable when there are dual chiral centers in X and G1the provisions of attachment.

The invention also encompasses a pharmaceutical composition that contains a compound of formula I in combination with a pharmaceutically suitable carrier.

Preference is sustained fashion composition comprises pharmaceutically suitable carrier and a non-toxic therapeutically effective amount of the compounds of formula I, described above (or its pharmaceutically acceptable salt).

In addition, in the context of the preferred embodiment of the invention includes a pharmaceutical composition for treating diseases by inhibition of the enzyme cytochrome P450RAI, resulting in the regulation and differentiation of epithelial cells containing a pharmaceutically suitable carrier and a non-toxic therapeutically effective amount of the compounds of formula I, which describe above (or its pharmaceutically acceptable salt).

The term "pharmaceutically acceptable salt" refers to salts derived from pharmaceutically suitable non-toxic bases or acids. If the connection of the present invention is acidic, its corresponding salt is usually obtained with a pharmaceutically suitable non-toxic bases, including inorganic bases and organic bases. Salts derived from such inorganic bases include salts of aluminum, ammonium, calcium, copper (divalent and trivalent), ferric, dvuhletnego iron, lithium, magnesium, manganese (trivalent and divalent), potassium, sodium, zinc and the like salts. Particularly preferred are the salts of ammonium, calcium, magnesium, potassium and sodium. Salts derived from pharmaceutically suitable non-toxic the organic bases, include salts of primary, secondary and tertiary amines, and cyclic amines and substituted amines, such as natural and synthesized substituted amines. Other pharmaceutically suitable organic non-toxic bases, which may be a salt formed include ion exchange resins, such as arginine, betaine, caffeine-, choline-, N',N'-dibenziletilendiaminom, diethylamin-, 2-Diethylaminoethanol-, 2-dimethylaminoethanol, ethanolamine, Ethylenediamine-N-ethylmorpholine-, N-ethylpiperidine, glucamine, glucosamine, histidine-, geranamine-, Isopropylamine, lysine, methylglucamine, morpholine, piperazine-, piperidine-, polyamine-resins, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine and the like.

If the connection of the present invention is basic, its corresponding salt can usually be obtained with a pharmaceutically suitable non-toxic acids, including inorganic and organic acids. Such acids include, for example, acetic, benzosulfimide, benzoic, camphorsulfonic, lemon, econsultancy, formic, fumaric, gluconic, Hydrobromic, hydrochloric, isetionate, lactic, maleic, malic, almond, methansulfonate, mucus, nitrogen, pambou, Pantothenic, phosphoric, succinic, ser is th, wine, p.-toluensulfonate acid and the like. Preferred are citric, Hydrobromic, formic, hydrochloric, maleic, phosphoric, sulfuric and tartaric acids. Particularly preferred are formic and hydrochloric acid.

The pharmaceutical compositions of this invention contain the compound represented by the formula I (or pharmaceutically acceptable salt, as an active ingredient, a pharmaceutically suitable carrier and, optionally, other ingredients or adjuvants. The compositions include compositions suitable for oral, rectal, local and parenteral (including subcutaneous, intramuscular and intravenous) administration, although the most suitable method in each case will depend on the particular host and the nature and severity of the condition, for which introduce the active ingredient. Pharmaceutical compositions typically can be in a standard dosage form and may be prepared by any methods known in the pharmaceutical field.

In practice, the compounds of formula I or their pharmaceutically suitable salts according to the invention can be combined as the active ingredient in a homogeneous mixture with a pharmaceutical carrier according to conventional pharmaceutical methods of making the composition. N is Khabibullina, you can choose from a great variety of forms depending on the form of the drug, required for administration, for example oral, or parenteral (including intravenous). Thus, the pharmaceutical compositions of this invention can be in the form of separate forms suitable for oral administration such as capsules, starch wafers or tablets, each of which contains a preset amount of the active ingredient. In addition, the composition can be in the form of powder, granules, solution, suspension in an aqueous liquid, in the form of non-aqueous liquids, emulsions of the type oil-in-water or a liquid emulsion of the type water-in-oil. In addition to conventional dosage forms listed above, the compound of formula I or its pharmaceutically acceptable salt can also be entered by means of supervised release and/or delivery devices. The composition can be prepared by any methods known in the field of pharmacy. In General, such methods include the stage of formation of bridging ties in Association the active ingredient with the carrier which constitutes one or more necessary ingredients. Generally, the composition is prepared at a constant and uniform mixing of the active ingredient with liquid carriers or finely ground solid carriers or both. The product then can be easily formed in the desired form.

Thus, pharmac ticheskie compositions of this invention may include pharmaceutically suitable carrier and a compound or pharmaceutically acceptable salt of formula I. The compounds of formula I or its pharmaceutically suitable salts can also be included in pharmaceutical compositions in combination with one or more therapeutically active compounds.

Used in the pharmaceutical carrier may be, for example, solid, liquid and gas. Examples of solid carriers include lactose, white earth, sucrose, talc, gelatin, agar, pectin, Arabic gum, magnesium stearate and stearic acid. Examples of liquid carriers are sugar syrup, peanut butter, olive oil and water. Examples of gaseous carriers include carbon dioxide and nitrogen.

For preparation of compositions for oral dosage forms can use any of the usual pharmaceutical environment. For example, you can use water, glycols, oils, alcohols, flavouring tools, dyes and the like, to prepare oral liquid preparations such as suspensions, elixirs and solutions, while carriers such as starches, sugars, microcrystalline cellulose, diluents, granulating tools, lubricants, binders, dezintegriruetsja tools and the like, can be used to prepare oral solid preparations such as powders, capsules and tablets. Due to the ease of the introduction of tablets and capsules represent the PR is doctitle oral dosage forms, employ solid pharmaceutical carriers. Probably, the tablets can be coated using standard aqueous and non-aqueous methods.

Tablet containing composition of this invention can be prepared by compaction or extrusion, possibly with one or more auxiliary ingredients or adjuvants. Compacted tablets can be prepared by compression in the respective machine, the active ingredient in free-flowing form such as powder or granules, possibly mixed with a binder, lubricant, inert diluent, surface active or dispersing agent. Compressed tablets can be prepared by pressing in the appropriate machine, the mixture of the powdered compound moistened inert liquid diluent. Each tablet preferably contains from about 0.05 mg to 5 g of active ingredient, and each starch wafer or capsule preferably contains from about 0.05 mg to 5 g of the active ingredient.

For example, a drug intended for oral administration to humans may contain from about 0.5 mg to 5 g of the active substance mixed with an appropriate and generally accepted number of media, which may vary from about 5 to 95 percent of the entire composition. Standard dosage forms usually is, may contain from about 1 mg to 2 g of active ingredient, typically 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg or 1000 mg

The pharmaceutical compositions of this invention suitable for parenteral administration can be prepared as solutions or suspensions of the active compounds in water. You can include a suitable surfactant, such as hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof in oils. You can also include preservatives to prevent harmful microbial growth.

The pharmaceutical compositions of this invention suitable for use in injection include sterile aqueous solutions or dispersions. In addition, the composition can be in the form of sterile powders for impromptu cooking such sterile injectable solutions or dispersions. In all cases, the final injectable form must be sterile and should really be liquid for easy injection with a syringe. The pharmaceutical compositions should be stable under conditions of manufacture and storage; therefore, it is preferable to keep from contaminating action of microorganisms, such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example the EP, glycerin, propylene glycol, and liquid polyethylene glycol), vegetable oils and their suitable mixtures.

The pharmaceutical compositions of this invention can be in a form suitable for topical application, such as an aerosol, cream, ointment, lotion, powder and the like. In addition, the composition can be in a form suitable for use in transdermal devices. These preparations can be prepared using the compound of formula I of this invention or its pharmaceutically acceptable salt by conventional processing methods. For example, a cream or ointment is prepared by mixing the hydrophilic material and water together with from about 5 to 10 wt.% connection to get the cream or ointment desired consistency.

The pharmaceutical compositions of this invention can be in a form suitable for rectal administration, in which the carrier is a solid. Preferably the mixture is formed into a standard metered dose suppositories. Suitable carriers include cocoa butter and other materials commonly used in this field. Suppositories usually can be prepared first by mixing the composition with the softened or melted carrier(s) followed by chilling and making some form in the matrix.

Apart from the aforementioned media-ingred the clients considered pharmaceuticals, when necessary, can include one or more additional media-ingredients, such as diluents, buffer funds, flavouring tools, binders, surfactants, thickeners, lubricants, preservatives (including antioxidants) and the like. In addition, other adjuvants can be incorporated in order to make the drug isotonic blood of the intended recipient. The compositions containing the compound of formula I or its pharmaceutically suitable salts can be prepared in powder or concentrated liquid form.

In General, the dose levels of the order from about 0.01 mg/kg to 150 mg/kg body weight on day of use in the treatment of the above conditions, or alternatively about 0.5 mg to 7 g per patient per day. For example, skin diseases and cancer can be treated effectively by the introduction of approximately from 0.01 to 50 mg of compound per kilogram of body weight per day or alternatively about 0.5 mg to about 3.5 g per patient per day.

However, it is clear that special level of dosage for any particular patient will depend upon a number of factors, including the age, body weight, General health, sex, diet, time of administration, route of administration, rate of excretion, drug combination and severity of certain diseases, to the which they treat.

BIOLOGICAL STUDIES

The efficiency of the examples of the invention, compounds of formula I as inhibitors of Cyp26 demonstrated by a number of pharmacological studies in vitro. These studies and their respective methods carried out with the compounds according to the invention. Activity is exhibited by compounds of the formula I can be demonstrated in vivo.

Biochemical in vitro

The compounds of formula I can inhibit the activity of CYP26. Biochemical in vitro study was performed using microsomal preparations from T47D cells, which induced the expression of CYP26. The enzymatic activity was estimated as the conversion of radiolabelled substrate to its metabolite, 4-OH RA (4-hydroxy all TRANS-retinoic acid and 4-oxo RA (4-oxo-retinoic acid) when separated by HPLC on a C18 column. Inhibition of CYP26 activity in the presence of different concentrations of similar naphthalene used to determine the values of the IC50.

WAYS

Microsomal preparation from cells T47D

The T47D cells were grown in RPMI medium 1640 containing 10% FBS and 1% P/S, were sown on the Cup and through 16-25 hours were treated with 5 μm atRA and left to incubate for an additional 48 hours before harvesting the cells. Cells were twice washed in 1 x PBS and suckable is Ali from cups. Cells were besieged and re-suspended in the buffer for homogenization (0.1 M Tris-Cl, pH 7.4, 0.1 M DTT, 0.2 mm EDTA, 1,15% wt./about. KCl, 0.1 mm PMSF and 20% vol./about. glycerine). Microsome assay were obtained by differential centrifugation of homogenised cells. Homogen was centrifuged at 17000 g, and the supernatant was again centrifugally at 100000 g. The precipitate is re-suspended in 25 mm potassium phosphate, pH 7.4, 20% vol./about. glycerol and kept at -80°C.

Biochemical analysis of CYP26 by HPLC

Enzymatic studies were performed in a reaction mixture composed of 100 mm Tris, pH 7.4, 150 mm KCl, 10 mm MgCl2, 2 mm NADPH, 40 nm 3H-atRA, a total volume of 100 μl, and with different concentrations of the new compounds dissolved in DMSO so that the final concentration in the reaction mixture was 1%, and with 20 μg of microsomal T47D. The reaction mixture was incubated at 37°C for 30 minutes in the dark. The reaction was stopped by adding 125 μl of acetonitrile were mixed and centrifuged at 10,000 g for 10 minutes. The supernatant was removed, and atRA and metabolites were separated on a C18 column Waters Spherisorb with linear radiometric detector at a flow rate of 1 ml/min and was determined at 350 nm. Used gradient was a mixture of 60 mm ammonium acetate, pH 5,2/30% CH3HE, solvent a and solvent B (CH3IT). The gradient of 30-50% CH3HE spent over 8 mine the subsequent gradient 50-99% CH 3HE spent 4 minutes and 99% of CH3IT within 2 minutes.

Inhibition of cell proliferation in vitro

New naphthalene analogues inhibit the proliferation of breast cancer cells and prostate cancer in vitro. The experiments were conducted on the lines of cancer cells breast cancer T47D and line cell adenocarcinoma of the prostate of the rat AT.

WAYS

The T47D cells were grown in RPMI medium 1640 containing 10% FBS and 1% P/S. Cells were placed in 96-well culture plates (2000 cells per well) in 100 μl of the same medium. After attaching for 16-24 hours, the filler (DMSO) or atRA (at a concentration of from 1 nm to 1 μm), or atRA in the same concentrations, in combination with changing concentration of the new compounds were added to the wells in three copies (J. Biol. Chem. 1997, 272(29), 17921-17928). Environment/treatment was repeated 3 days after the first treatment, and evaluation of reduction of cell proliferation was performed after 48 hours, using cellular titrator CellTiter-GloTM(Promega).

The above method is also used for cell AT except that the cells were placed in the plate at a concentration of 1500 cells per well, and the treatment was performed once with the assessment of the reduction of cell proliferation after 72 hours after treatment. Cells AT were grown in RPMI medium 1640 containing 10% FBS, 1% P/S and 250 nm dexamethasone.

The study CYP3A4

DL the assessment of inhibition of CYP3A4 activity enzymatic studies were performed in a volume of 100 μl in 96-well tablets using the fluorescent substrate (BD, Gentest). Compounds were tested at various concentrations in the reaction mixture, which contained 200 mm potassium phosphate buffer, pH 7.4, 200 mm NADPH and 50 μm 7-benzyloxy-4-(trifluoromethyl)-coumarin. The reaction mixture was incubated at 37°C for 45 minutes followed by the addition of 37 μl of 0.5 M Tris-base, to complete the reaction. Tablets read at excitation/emission 405/535 nm, respectively.

All examples have demonstrated the inhibition of Cyp26. The following examples show the efficiency and activity in the inhibition of Cyp26 for biochemical analysis in the concentration range from about 5 μm to below 10 nm. The most preferred examples were selective about Cyp26. Preferably, when the ratio of the magnitude of IC50for Cyp3A4 activity to the magnitude of the IC50for Cyp26 activity is 10:1 or higher, or 100:1 or higher.

EXPERIMENTAL PART

The diagrams 1-29 below, which shows how to synthesize the compounds of this invention and below in tables 1-5, in which are shown various representative compounds of this invention used the following abbreviations: Me is methyl, Et is ethyl,iPr oriPr for isopropyl, n-Bu is n-butyl, t-Bu is tert-butyl, Ac is acetyl, Ph is phenyl, 4Cl-Ph or (4Cl)Ph - 4-chlorophenyl, 4Me-Ph or (4Me)Ph - 4-were, (p-CH3O)Ph - p-methoxyphenyl, p-NO2)P - p-nitrophenyl, 4Br-Ph or (4Br)Ph - 4-bromophenyl, 2-CF3-Ph or (2CF3)Ph - 2-triptoreline, DMAP is 4-(dimethylamino)pyridine, DCC is 1,3-dicyclohexylcarbodiimide, EDC hydrochloride, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, HOBt is 1-hydroxybenzotriazole, HOAt is 1-hydroxy-7-asobancaria, CDI is 1,1'-carbonyldiimidazole, CDT - 1,1'-carbonelli(1,2,4-triazole), DEAD - diethylazodicarboxylate, DIAD - diisopropylsalicylic, DBAD - di-tert-butyl-azodicarboxylate, FBS - fetal bovine serum, P/S - penicillin/streptomycin, DTT - dithiothreitol, EDTA - ethylenediaminetetraacetic acid, PMSF - phenylmethylsulfonyl, Tris - trimethylamine, NADPH - restored beta nicotinamide adenindinucleotide phosphate and Bn is benzyl.

The following outlines the methods are specific compounds that are used as intermediates in the creation of inhibiting Cyp26 examples. Such intermediates are included in this invention.

The compounds of formula I of this invention and the intermediates used in the synthesis of compounds of the present invention, was obtained in accordance with the following methods. Method And used to obtain compounds of formula I-A [the compounds of formula I in which R1corresponds to N; R4a, R5a, R6aand R6bcorrespond to N, and Y means O], as shown in the following scheme 1:

Method a:

SCHEME 1

where X, R2, R3, G1, (Z)n2, (CR4bR5b)n3and (Q1)n4are as previously described for the compounds of formula I.

A typical way to obtain the compound of formula II was introduced in the reaction with CDI or CDT in a suitable solvent. Suitable solvents for use in the above method include ethers such as tetrahydrofuran (THF), glyme, and the like; dimethylformamide (DMF); dimethyl sulfoxide (DMSO); acetonitrile and chlorinated solvents such as methylene chloride (CH2Cl2) or chloroform (CHCl3), not limited to these solvents. If needed, used a mixture of these solvents. The preferred solvent depends on the used substrates, and he was selected in accordance with properties of the substrates. The above method is carried out at temperatures between about -78°C and 100°C. Preferably the reaction was carried out at a temperature between about 22°C and 80°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Essentially, preferably used equimolar amount reacherous the substances, although, if necessary, apply a higher or lower number.

[252] the compounds of formula II, scheme 1 was obtained, as shown in the following scheme 2.

SCHEME 2

in which R2, R3, G1, (Z)n2, (CR4bR5b)n3and (Q1)n4are as previously described for the compounds of formula I.

A typical way to obtain the compounds of formula II, the compound of formula III is treated with a suitable regenerating reagent in a suitable solvent, with a suitable reducing reagents include reducing reagents, boron derivative, such as sodium borohydride, lithium borohydride, borane, and the like; reducing agents, derivatives of aluminum, such as lithium hydride aluminum, Alan, hydride, lithium tri-tert-butoxy-aluminum and the like, but is not limited to; hydrogenation over a metal catalyst such as palladium on carbon. Preferred regenerating reagent was sodium borohydride. Suitable solvents for use in the above method include ethers such as tetrahydrofuran (THF), glyme, and the like, alcohol solvents such as methanol, ethanol, isopropanol and the like, but is not limited to; however, the typical response is rowdily in methanol. The above method is performed at temperatures between about -78°C and 100°C. Preferably the reaction was carried out at a temperature of approximately between 0°C and 20°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at atmospheric pressure, although if necessary you can use a higher or lower pressure. Essentially, preferably used equimolar amounts of reactants, although if necessary it is possible to apply a higher or lower number.

The compounds of formula III in scheme 2 was obtained, as shown in the following scheme 3:

SCHEME 3

where R2, R3, G1, (Z)n2, (CR4bR5b)n3and (Q1)n4are as previously described for the compounds of formula I and A1=OH, OTs, OMs or halogen.

When usual obtain the compounds of formula III (when A1=halogen in the compound of formula (V) compound of formula IV interacted with the compound of the formula V (where A1=halogen) in a suitable solvent in the presence of an appropriate base. Suitable solvents for use in the above method include ethers such as tetrahydrofuran (THF), glyme, and the like; dimethylformamide (DMF); dimethyl sulfoxide (DMSO); acetonitrile (CH3CN) the chlorinated solvents, such as methylene chloride (CH2Cl2) or chloroform (CHCl3), without limitation. If necessary, you can use a mixture of these solvents. The preferred solvent was DMF or CH3CN. Suitable bases for use in the above method include metal hydrides such as sodium hydride or potassium hydroxide; alkoxides of metals such as alkoxides of sodium or potassium hydroxide; hydroxides of alkaline metals such as sodium hydroxide or potassium hydroxide; tertiary amines, such as triethylamine or diisopropylethylamine; carbonates of alkali metals such as sodium carbonate or potassium hydroxide or pyridine, is not limited to the aforementioned. If needed, used a mixture of these bases. The preferred base was sodium hydride or tert-piperonyl potassium. The above method is performed at temperatures between about -78°C and 100°C. Preferably the reaction was carried out at a temperature of approximately between 0°C and 50°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at atmospheric pressure, although if necessary you can use a higher or lower pressure. Essentially, preferably used equimolar amounts of reactants, although optionally used higher or lower to what icesta. Usually one equivalent of base was taken as the equivalent of starting material of the compounds of formula IV.

When usual obtain the compounds of formula III (when A1=OH in the compound of formula (V) compound of formula IV interacted with the compound of the formula V (where A1=OH) in a suitable solvent in the presence of appropriate reagents. Suitable solvents for use in the above method include ethers such as tetrahydrofuran (THF), glyme, and the like; dimethylformamide (DMF), dimethylsulfoxide (DMSO), acetonitrile (CH3CN) and chlorinated solvents such as methylene chloride (CH2Cl2) or chloroform (CHCl3), without limitation. If necessary, used a mixture of these solvents, however, the preferred solvent was THF. Suitable reagents for use in the above method include triphenylphosphine and azodicarboxylate (DIAD, DEAD, DBAD), not limited to the above reagents. Desirable reagents were triphenylphosphine and DIAD. The above method is performed at temperatures between about -78°C and 100°C. Preferably the reaction was carried out at a temperature of approximately between 0°C and 50°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric the pressure, although having used a higher or lower pressure. Essentially, preferably used equimolar amounts of reactants, although if necessary, apply a higher or lower number. Usually one equivalent of triphenylphosphine, DIAD, and the compounds of formula V was taken as the equivalent of starting material of the compounds of formula IV. The compounds of formula V is usually bought or received in accordance with known methods (Tetrahedron Letters, 1999, 40, 5467-5470).

The compounds of formula IV in scheme 3 was obtained, as shown in the following scheme 4:

SCHEME 4

where R2, R3and G1are as described previously for compounds of formula I and A2=C1-6the alkyl or aryl-C1-6-alkyl.

When usual obtain the compounds of formula IV, the compound of formula VI was introduced into the reaction under suitable conditions for the conversion of the A2to N. Suitable reagents for the conversion of the A2to N in the above method include the pyridine-HCl, BBr3, AlCl3and HBr/acetic acid. The preferred condition was treatment of compounds of formula VI with a mixture of 48% aqueous HBr/acetic acid. The above method is performed at temperatures between about 50°C. and 150°C. Preferably, the reaction was carried out at a temperature between approximately 100°C. and 120°C. Above the aforementioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although having used a higher or lower pressure. Essentially, preferably used equimolar amounts of reactants, although if necessary, apply a higher or lower number. Usually an excess of a mixture of 48% aqueous HBr/acetic acid was taken as the equivalent of starting material of compound of formula VIII.

The compounds of formula VI scheme 4 received, as shown in the following scheme 5:

SCHEME 5

where R2, R3and G1are as described previously for compounds of formula I and A2=C1-6-alkyl or aryl-C1-6-alkyl and A3=suitable leaving group such as halogen.

When usual obtain the compounds of formula VI, a compound of formula VII was introduced into the reaction c H-G1in a suitable solvent in the presence of an appropriate base. Suitable solvents for use in the above method include ethers such as tetrahydrofuran (THF), glyme, diethyl ether, dioxane and the like; aromatic solvents such as benzene and toluene; acetonitrile; chlorinated solvents such as methylene chloride (CH2Cl2), carbon tetrachloride (CCl4) or chloroform (CHCl3), not limited to the aforementioned. If necessary, used a mixture of listed is rastvoritelei, however, the preferred solvent was a mixture of methanol/chloroform. Suitable catalysts for use in the above method include tetrabutylammonium iodide or NaI, not limited to the aforementioned. If necessary, used a mixture of these catalysts, however, the preferred catalyst was NaI. Suitable bases for use in the above method include metal hydrides such as sodium hydride or potassium hydroxide; alkoxides of metals such as alkoxides of sodium or potassium hydroxide; hydroxides of alkaline metals such as sodium hydroxide or potassium hydroxide; tertiary amines, such as triethylamine or diisopropylethylamine; a carbonate of an alkali metal such as sodium carbonate or potassium; or pyridine, without limitation. If necessary, used a mixture of these bases, however, the preferred base was diisopropylethylamine or H-G1if G1=NR7R8. The above method is performed at temperatures between -78°C and 100°C. Preferably the reaction was carried out at a temperature of approximately between 0°C and 100°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Essentially, preference is sustained fashion used equimolar amounts of reactants, although, if necessary, apply a higher or lower number. Normally, the catalyst is used in lower amounts than the amounts of the compounds of formula VII, and H-G1. Usually bought commercial preparation H-G1or H-G1received in accordance with known methods. The compounds of formula VII was obtained in accordance with known literature methods (Sonawane, H.R.; et al. Tetrahedron, 1994, 50(4), 1243-1260).

The compounds of formula VII of figure 5 was obtained, as shown below in scheme 6A:

SCHEME 6A

in which R2and R3are such as previously described for the compounds of formula I, A2=C1-6-alkyl or aryl-C1-6-alkyl, and A3and A5=suitable leaving group such as halogen, and A4=halogen or OTf.

When usual obtain the compounds of formula VII compound of formula VIII was introduced into the reaction with organolithium reagent or a metal catalyst followed by reaction with a compound of formula IX in a suitable solvent. Suitable solvents for use in the above method include ethers such as tetrahydrofuran (THF), glyme, diethyl ether, dioxane and the like; aromatic solvents such as benzene and toluene, is not limited to these solvents. If necessary, the COI is litovali a mixture of these solvents, however, the preferred solvent was THF. Suitable varieties orginality or metals for use in the above method include varieties orginality, such as n-butyl lithium or tert-butyl lithium; magnesium. Preferred metal catalyst was magnesium. The above method is performed at temperatures between about -78°C and 100°C. Preferably the reaction was carried out at a temperature of approximately between 0°C and 100°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Essentially, preferably used equimolar amounts of reactants, although if necessary, apply a higher or lower number. Magnesium is typically used in amounts exceeding the amounts of the compounds of formula VIII. The compounds of formula VIII and IX are usually bought or received in accordance with known methods.

Alternative compounds of formula VI of figure 5 was obtained, as shown below in scheme 6b:

SCHEME 6B

in which R2, R3and G1are such as previously described for the compounds of formula I, A2=C1-6-alkyl or aryl-C1-6-alkyl, AA 4=halogen or OTf.

When usual obtain the compounds of formula VI, a compound of formula VIII was introduced into reaction with a suitable organolithium reagent or a metal catalyst, followed by reaction with a compound of formula X in a suitable solvent. Suitable solvents for use in the above method include ethers such as tetrahydrofuran (THF), glyme, diethyl ether, dioxane and the like; aromatic solvents such as benzene and toluene, but is not limited to. If necessary, used a mixture of these solvents, however, the preferred solvent was THF. Suitable varieties orginality or metals for use in the above method include varieties orginality, such as n-butyl lithium or tert-butyl lithium; magnesium. The preferred connection orginality was tert-butyl lithium. The above method is performed at temperatures between about -78°C and 100°C. Preferably the reaction was carried out at a temperature between about -78°C and 50°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Essentially, preferably used is whether equimolar amounts of reactants, although, if necessary, apply a higher or lower number. The compounds of formula VIII and X are usually bought or received in accordance with known methods.

The compounds of formula III of this invention and the intermediates used in the synthesis of compounds of this invention were obtained by the following methods.

The method used for obtaining the compounds of formula III, as shown in the following scheme 7:

METHOD:

SCHEME 7

where R2, R3, G1, (Z)n2, (CR4bR5b)n3and (Q1)n4are such as previously described for the compounds of formula I and A3=halogen.

When usual obtain the compounds of formula III according to the method In scheme 7, the compound of formula XI was introduced into the reaction with H-G1in a suitable solvent in the presence of an appropriate base. Suitable solvents for use in the above method include ethers such as tetrahydrofuran (THF), glyme, diethyl ether, dioxane and the like; aromatic solvents such as benzene and toluene; acetonitrile; chlorinated solvents such as methylene chloride (CH2Cl2), carbon tetrachloride (CCl4) or chloroform (CHCl3), without limitation. If necessary, used a mixture of named is rastvoritelei, however, the preferred solvent was a mixture of acetonitrile. Suitable catalysts for use in the above method include tetrabutylammonium iodide or NaI. If necessary, used a mixture of these catalysts, however, the preferred catalyst was NaI. Suitable bases for use in the above method include metal hydrides such as sodium hydride or potassium hydroxide; alkoxides of metals such as alkoxides of sodium or potassium hydroxide; hydroxides of alkaline metals such as sodium hydroxide or potassium hydroxide; tertiary amines, such as triethylamine or diisopropylethylamine; a carbonate of an alkali metal such as sodium carbonate or potassium; or pyridine. If necessary, used a mixture of these bases, however, the preferred base was diisopropylethylamine or H-G1if G1=NR7R8. The above method is performed at temperatures between -78°C and 100°C. Preferably the reaction was carried out at a temperature of approximately between 0°C and 100°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Essentially, preferably used equimolar amounts of reactants, although when dealing with used a higher or lower number. The catalyst is usually used in smaller quantities than the number of the compounds of formula XI, and H-G1. Usually bought commercial preparation H-G1or received by known methods.

The compounds of formula XI scheme 7 was obtained as described below in scheme 8:

SCHEME 8

where R2, R3, (Z)n2, (CR4bR5b)n3and (Q1)n4are as previously described for the compounds of formula I and A3=halogen.

When usual obtain the compounds of formula XI, a compound of formula XI was introduced into reaction with a suitable halogenation reagent in a suitable solvent. Suitable halogenation reagents include Br2, Cl2, N-bromosuccinimide, N-chlorosuccinimide, chloride Sulfuryl and CuBr2. Suitable solvents for use in the above method include ethers such as tetrahydrofuran (THF), dioxane, glyme, diethyl ether and the like; acetonitrile; chlorinated solvents such as methylene chloride (CH2Cl2) or chloroform (CHCl3), without limitation. If necessary, used a mixture of these solvents, however, the preferred solvent was dioxane. The above method is performed at temperatures between -78°C and 150°C. Preferably the reaction is rowdily at a temperature of approximately between 80°C and 150°C. The aforementioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Essentially, preferably used equimolar amounts of reactants, although if necessary, applied higher and lower amounts. Usually used two equivalent CuBr2the equivalent of starting material of compound of formula XII.

The compounds of formula XII in scheme 8 was obtained, as shown below in scheme 9:

SCHEME 9

where R2, R3, (Z)n2, (CR4bR5b)n3and (Q1)n4are as previously described for the compounds of formula I and A1=halogen or HE.

When usual obtain the compounds of formula XII (A1in the compound of formula V means halogen) compound of formula XIII interacted with the compound of the formula V (A1=halogen) in a suitable solvent in the presence of an appropriate base. Suitable solvents for use in the above method include ethers, like tetrahydrofuran (THF), glyme, and the like; dimethylformamide (DMF), dimethylsulfoxide (DMSO); acetonitrile (CH3CN); chlorinated solvents such as methylene chloride (CH2 Cl2) or chloroform (CHCl3), without limitation. If necessary, used a mixture of these solvents. The preferred solvent was DMF or CH3CN. Suitable bases for use in the above method include metal hydrides such as sodium hydride or potassium hydroxide; alkoxides of metals such as alkoxides of sodium or potassium hydroxide; hydroxides of alkaline metals such as sodium hydroxide or potassium hydroxide; tertiary amines, such as triethylamine or diisopropylethylamine; a carbonate of an alkali metal such as sodium carbonate or potassium; or pyridine. If necessary, used a mixture of these bases. The preferred base was sodium hydride or tert-piperonyl potassium. The above method is performed at temperatures between -78°C and 100°C. Preferably the reaction was carried out at a temperature of approximately between 0°C and 50°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Essentially, preferably used equimolar amounts of reactants, although if necessary, applied higher and lower amounts. Usually used one equivalent of base per equivalent of the original is the material of the compounds of formula XIII.

When usual obtain the compounds of formula XII (A1=HE is in the connection formula (V), the compound of formula XIII interacted with the compound of the formula V (A1=HE) in a suitable solvent in the presence of appropriate reagents. Suitable solvents for use in the above method include ethers, like tetrahydrofuran (THF), glyme, and the like; dimethylformamide (DMF), dimethylsulfoxide (DMSO); acetonitrile (CH3CN); chlorinated solvents such as methylene chloride (CH2Cl2) or chloroform (CHCl3), without limitation. If necessary, used a mixture of these solvents, however, the preferred solvent was THF. Suitable reagents for use in the above method include triphenylphosphine and azodicarboxylate (DIAD, DEAD, DBAD). Desirable reagents were triphenylphosphine and DIAD. The above method is performed at temperatures between -78°C and 100°C. Preferably the reaction was carried out at a temperature of approximately between 0°C and 50°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Essentially, preferably used an equimolar amount the VA reagents although having used the higher and lower amounts. Usually used one equivalent of triphenylphosphine, DIAD, and the compounds of formula V to the equivalent of starting material of compound of formula XIII. Usually bought commercial compounds of formula V and XIII, or these compounds were obtained by known methods.

The method used for obtaining the compounds of formula I-B [the compound of the formula I, in which R1corresponds to H, n1=1, R4a, R5a, R6aand R6bmatch N, Y means O, n4=1, Q1=CO2H], as shown below in scheme 10:

The METHOD:

SCHEME 10

where X, R2, R3, G1, (Z)n2, (CR4bR5b)n3are as previously described for the compounds of formula I, and R7=alkyl.

Under normal retrieval method With the compounds of formula I-B [the compound of the formula I, in which R1means H, n1 =1, R4a, R5a, R6aand R6bmatch N, Y means O, n4=1, Q1=CO2H] the compound of formula I-A [the compounds of formula I in which R1means H, n1 =1, R4a, R5a, R6aand R6bmatch N, Y means O, n4=1, Q1=CO2R7] engaged in basic or acidic conditions in a suitable solvent. Suitable solvents for use in the above SPO is both include ethers, as tetragidrofuran (THF), glyme, and the like; dimethylformamide (DMF), dimethylsulfoxide (DMSO); acetonitrile; alcohol solvents such as methanol, ethanol and the like, without limitation. If necessary, used a mixture of these solvents, however, the preferred solvent was a mixture of water, THF and methanol. The basic conditions for use in the above method include the use of alkoxides, such as sodium alkoxides or potassium, and hydroxides of alkali metals such as sodium hydroxide or potassium hydroxide in water. Acidic conditions for use in the above method included the use of hydrochloric acid solutions. The above method is performed at temperatures between 0°C and 80°C. Preferably the reaction was carried out at a temperature between about 22°C and 70°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at atmospheric pressure, although if necessary, used a higher or lower pressure. Mainly used equimolar amounts of reactants, although if necessary, used a higher or lower number.

Method D was used for obtaining the salts of the compounds of the formula I-(HA6)n7as shown below in scheme 11:

The WAY D:

SCHEME 11

where X, R1, R2, R3, G1, Y (CR4aR5a)n1, (Z)n2, (CR4bR5b)n3(Q1)n4, R6aand R6bare as previously described for the compounds of formula I, n7=1 or 2 and A6=protivoiona N, including, for example, chloride or formate.

Under normal retrieval method D compounds of the formula I-(HA6)n7the compound of formula I interacted with a suitable acid, HA6in a suitable solvent. Suitable solvents for use in the above method include ethers, as tetragidrofuran (THF), glyme, diethyl ether and the like; acetonitrile; water; alcohol solvents such as methanol, ethanol and the like, without limitation. If necessary, used a mixture of these solvents, however, the preferred solvents were or diethyl ether, methanol or water. HA6is the corresponding pharmaceutically acceptable acid, which is formed corresponding mono - or dial the compounds of formula I-(HA6)n7. The above method is performed at temperatures between 0°C and 60°C. Preferably the reaction was carried out at a temperature of approximately between 0°C and 25°C. the Above-mentioned method of producing compounds of the present invention preferably OS is Westley at atmospheric pressure, although having used a higher or lower pressure. Mainly used equimolar amounts of reactants, although if necessary, used a higher or lower number. Acid HA6usually bought or received by known methods.

Method E was used when obtaining the compounds of formula I-D [compounds of formula I in which R1corresponds to H, n1=1, R4a, R5a, R6aand R6bmatch N, Y means O, n4=1, Q1=CONR7R8]as shown below in scheme 12:

The WAY E:

SCHEME 12

where X, R2, R3, G1, (Z)n2, R7, R8and (CR4bR5b)n3are as previously described for the compounds of formula I.

Under normal retrieval method E. the compounds of formula I-D [compounds of formula I in which R1means H, n1 =1, R4a, R5a, R6aand R6bmatch N, Y means O, n4=1, Q1=CONR7R8] the compound of formula I-B [the compound of the formula I, in which R1means H, n1 =1, R4a, R5a, R6aand R6bmatch N, Y means O, n4=1, Q1=CO2H] was introduced into the reaction under appropriate conditions with HNR7R8to obtain the compound of formula I-D. Suitable conditions include treatment of the compound forms of the crystals I-B chloride tonila, a mixture of triphenylphosphine/carbon tetrachloride, CDI or diphenylphosphorylacetate not limited to the aforementioned compounds, to obtain the activated species of the carbonyl, followed by treatment HNR7R8. The preferred reaction condition was the reaction of the compounds of formula I-B with CDI followed by treatment HNR7R8. Suitable solvents for use in the above method include ethers, such as tetragidrofuran (THF), glyme, and the like; dimethylformamide (DMF); dimethyl sulfoxide (DMSO): acetonitrile; halogenated solvents such as chloroform or methylene chloride. If necessary, used a mixture of these solvents, however, the preferred solvent was acetonitrile. The above method is performed at temperatures between approximately 0°C and 80°C. Preferably the reaction was carried out at a temperature between about 22°C and 80°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at atmospheric pressure, although if necessary, used a higher or lower pressure. Mainly used equimolar amounts of reactants, although if necessary, used a higher or lower number.

Additionally, when the conventional retrieval method E preprogram the Oia formula I-D [compounds of formula I, in which R1means H, n1 =1, R4a, R5a, R6aand R6bmatch N, Y means O, n4=1, Q1=CONR7R8] the compound of formula I-B [the compound of the formula I, in which R1means H, n1 =1, R4a, R5a, R6aand R6bmatch N, Y means O, n4=1, Q1=CO2H] worked under normal conditions of formation of amide to obtain the compound of formula I-D. Suitable conditions include treatment of the compounds of formula I-B and HNR7R8linking reagents such as DCC or EDC together with DMAP, HOBt, HOAt and the like, not limited to the aforementioned compounds. Suitable solvents for use in the above method include ethers, such as tetragidrofuran (THF), glyme, and the like; dimethylformamide (DMF); dimethyl sulfoxide (DMSO): acetonitrile; halogenated solvents such as chloroform or methylene chloride. If necessary, used a mixture of these solvents, however, the preferred solvent was DMF. The above method is carried out at temperatures between about 0°C. and 80°C. Preferably the reaction was carried out at a temperature between about 22°C and 80°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at atmospheric pressure, although if necessary the STI used a higher or lower pressure. Mainly used equimolar amounts of reactants, although if necessary, used a higher or lower number. Additionally, other suitable reaction conditions for the conversion of CO2H to CONR7R8can be found in Larock, R.C. Comprehensive Organic Transformations, 2nded., Wiley and Sons: New York, 1999, pp 1941-1949.

Alternative compounds of formula II, scheme 1 was obtained as shown in scheme 13.

SCHEME 13

where R2, R3, A3, G1, (Z)n2, (CR4bR5b)n3and (Q1)n4are as previously described for the compounds of formula I.

When usual obtain the compounds of formula II, the compound of formula XI was treated with a suitable regenerating reagent in an appropriate solvent, with a suitable reducing reagents include boron derivative, such as sodium borohydride, lithium borohydride, borane, and the like; reducing agents, derivatives of aluminum, such as lithium hydride aluminum, Alan, hydride, lithium tri-tert-butoxy-aluminum and the like, but is not limited to; hydrogenation over a metal catalyst such as palladium on carbon. Preferred regenerating reagent was sodium borohydride. Suitable solvents for use in the above method, VK is Uchali simple esters, such as tetrahydrofuran (THF), glyme, and the like, alcohol solvents such as methanol, ethanol, isopropanol and the like, not limited to the above solvents; however, the usual reaction was performed in methanol. The above method is carried out at temperatures between about -78°C and 100°C. Preferably the reaction was carried out at a temperature of approximately between 0°C and 20°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at atmospheric pressure, although if necessary, used a higher or lower pressure. Mainly used equimolar amounts of reactants, although if necessary, used a higher or lower number. As soon as considered that the recovery of the ketone to the alcohol ended, the reaction mixture was added HNR7R8in a suitable solvent. Suitable solvents for use in the above method include ethers, such as tetragidrofuran (THF), glyme, and the like; dimethylformamide (DMF); dimethyl sulfoxide (DMSO): acetonitrile (CH3CN); chlorinated solvents such as methylene chloride (CH2Cl2) or chloroform (CHCl3); alcohol solvents such as methanol, ethanol, isopropanol and the like. If necessary, used, see the si of the mentioned solvents, typically, however, the reaction was carried out in methanol. The above method is carried out at temperatures between about -78°C and 100°C. Preferably the reaction was carried out at a temperature of approximately between 0°C and 60°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at atmospheric pressure, although if necessary, used a higher or lower pressure. Mainly used equimolar amounts of reactants, although if necessary, used a higher or lower number. HNR7R8used in excess relative to the compound of formula XI, and it is usually purchased as a commercial product or received by known methods.

An alternative method F used to obtain compounds of formula I-A [the compounds of formula I in which R1means H, R4a, R5a, R6aand R6bmatch N, Y means O], as shown below in figure 14.

METHOD F

SCHEME 14

where X, R2, R3, G1, (Z)n2, (CR4bR5b)n3and (Q1)n4are such as previously described for the compounds of formula I and A1=OH, OTs, OMs or halogen.

Under normal getting under way F the compounds of formula I-A [the compound of the formula I, in which R1Osnach is et H R4a, R5a, R6aand R6bmatch N, Y means O] the compound of formula XIV interacted with the compound of the formula V (where A1=halogen) in a suitable solvent in the presence of an appropriate base. Suitable solvents for use in the above method include ethers, as tetragidrofuran (THF), glyme, and the like; dimethylformamide (DMF); dimethyl sulfoxide (DMSO): acetonitrile (CH3CN); chlorinated solvents, such as methylene chloride (CH2Cl2) or chloroform (CHCl3). If necessary, used a mixture of these solvents. The preferred solvent was DMF or CH3CN. Suitable bases for use in the above method include metal hydrides such as sodium hydride or potassium hydroxide; alkoxides of metals such as alkoxides of sodium or potassium hydroxide; hydroxides of alkaline metals such as sodium hydroxide or potassium hydroxide; tertiary amines, such as triethylamine or diisopropylethylamine; a carbonate of an alkali metal such as sodium carbonate or potassium; or pyridine. If necessary, used a mixture of these bases. The preferred base was sodium hydride or tert-piperonyl potassium. The above method is performed at temperatures between -78°C and 100°C. Preferably the reaction was carried out when the temperature is approximately between 0°C and 50°C. The aforementioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Essentially, preferably used equimolar amounts of reactants, although if necessary, applied higher and lower amounts. Usually used one equivalent of base per equivalent of starting material of compound of formula XIV.

When usual obtain the compounds of formula I-A [the compound of the formula I, in which R1means H, R4a, R5a, R6aand R6bmatch N, Y means O] the compound of formula XIV interacted with the compound of the formula V (in which A1=HE) in a suitable solvent in the presence of appropriate reagents. Suitable solvents for use in the above method include ethers, like tetrahydrofuran (THF), glyme, and the like; dimethylformamide (DMF), dimethylsulfoxide (DMSO); acetonitrile (CH3CN); chlorinated solvents, such as methylene chloride (CH2Cl2) or chloroform (CHCl3), not limited to these solvents. If necessary, used a mixture of these solvents, however, the preferred solvent was THF. Suitable reagents for skin is ment in the above method include triphenylphosphine and azodicarboxylate (DIAD, DEAD, DBAD). Desirable reagents were triphenylphosphine and DIAD. The above method is performed at temperatures between -78°C and 100°C. Preferably the reaction was carried out at a temperature of approximately between 0°C and 50°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Basically preferably used equimolar amounts of reactants, although optionally used higher and lower amounts. Usually took one equivalent of triphenylphosphine, DIAD, and the compounds of formula V by one equivalent of starting material of compound of formula XIV. Usually the compounds of formula V were commercial preparations or received by known methods.

The compounds of formula XIV in figure 14 was obtained as shown below in scheme 15:

SCHEME 15

where X, R2, R3and G1are as previously described for the compounds of formula I.

When usual obtain the compounds of formula XIV compound XV interacted with CDI or CDT in a suitable solvent. Suitable solvents for use in the above method include ethers such as tetrahydrofuran (THF), glyme, and the like; demetillo is mamid (DMF), dimethyl sulfoxide (DMSO); acetonitrile; chlorinated solvents such as methylene chloride (CH2Cl2) or chloroform (CHCl3), not limited to these solvents. If necessary, used a mixture of these solvents. The preferred solvent depended on the substrate used, and the solvent selected in accordance with properties of the substrate. The above method is performed at temperatures between -78°C and 100°C. Preferably the reaction was carried out at a temperature between about 22°C and 80°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Basically preferably used equimolar amounts of reactants, although optionally used higher and lower amounts.

The compounds of formula XV in scheme 15 was obtained as shown in scheme 16.

SCHEME 16

where R2, R3and G1are as previously described for the compounds of formula I.

When usual obtain the compounds of formula XV compound IV was treated with a suitable regenerating reagent in an appropriate solvent, and suitable restore the s reagents include derivatives of boron, such as sodium borohydride, lithium borohydride, borane, and the like, not limited to the aforementioned agents; reducing agents, derivatives of aluminum, such as lithium hydride aluminum, Alan, hydride, lithium tri-tert-butoxy-aluminum and the like; hydrogenation over a metal catalyst such as palladium on carbon. Preferred regenerating reagent was sodium borohydride. Suitable solvents for use in the above method include ethers such as tetrahydrofuran (THF), glyme, and the like, alcohol solvents such as methanol, ethanol, isopropanol and the like, not limited to the above solvents; however, the usual reaction was performed in methanol. The above method is carried out at temperatures between about -78°C and 100°C. Preferably the reaction was carried out at a temperature of approximately between 0°C and 20°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Mainly used equimolar amounts of reactants, although optionally used higher and lower amounts.

The compounds of formula I-Z (a compound of the formula I, in which R1 =OH, X=heteroaryl, Y=O, n1=1, and R6a, R6b, R4aand R5a=H) was obtained, as shown in scheme 17, following the reactions of a-C.

SCHEME 17

where X, R2, R3, G1, (Z)n2, (CR4bR5b)n3and (Q1)n4are such as previously described for the compounds of formula I and A1=suitable such substituted groups like halogen or triflate or deprotoniruya a hydrogen atom, d=0 or 1, R99=suitable protective group, such as benzyl or trityl, and M=metal including lithium and magnesium; metal salt, denoted by M, can include, for example, the halide of the metal, such as magnesium chloride, magnesium bromide or triflate magnesium.

When usual obtain the intermediate of formula XVII by reacting a compound of formula XVI is treated with a suitable connection alkyl-lithium and metal magnesium. Examples of such varieties of alkyl-lithium include n-utility, second-utility or tert-utility. Examples of the alkyl halide is magnesium include bromide of etermine or chloride Metalmania. Suitable solvents for use in the above method included such ethers, like tetrahydrofuran (THF), diethyl ether, dioxane and the like, saturated hydrocarbons such as hexane, pentane and the like; the hat aromatic hydrocarbons, as benzene or toluene, is not limited to these solvents. The above method is carried out at temperatures between about -40°C and 70°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Mainly used equimolar amounts of reactants, although if necessary, used a higher or lower number. In the case of alkyl-lithium, alkyl lithium is used in an amount of from 1 to 3 mol, preferably from 1 to 1.5 mol per one mol of starting material XVI.

Following the reaction In a typical obtaining the compounds of formula XVIII, the intermediate of formula XVII left to interact with the compound of the formula III. Suitable solvents for use in the above method include ethers such as tetrahydrofuran (THF), diethyl ether, dioxane and the like, saturated hydrocarbons such as hexane, pentane and the like; aromatic hydrocarbons such as benzene or toluene, is not limited to these solvents. The above method is carried out at temperatures between about -40°C and 70°C. the Above-mentioned method of producing compounds of the present invention preferably is sushestvovali approximately at atmospheric pressure, although having used a higher or lower pressure. Mainly used equimolar amounts of reactants, although if necessary, used a higher or lower number.

In accordance with the reaction With at normal connection I-Z compound of formula XVIII cultivated under conditions suitable for removing protection, to achieve the transformation R99in the hydrogen atom. For example, when d=1, and R99is a group of trityl, removal of protection made under acidic conditions or conditions suitable for hydrogenolysis. Examples of acidic conditions include the use of organic acids such as formic, acetic or triperoxonane acid, or the use of inorganic acids such as hydrochloric acid. Suitable solvents include alcohols, ethers or halogenated solvents. The above method is carried out at temperatures between about -40°C and 70°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Mainly used equimolar amounts of reactants, although if necessary, used a higher or lower number is STV. Examples A1-X-(R99)dnot limited to, include the following groups of heteroaryl:

Alternative compounds of formula XVII in scheme 17 received, as shown below in scheme 18:

SCHEME 18

where X, R2, R3, G1, (Z)n2, (CR4bR5b)n3and (Q1)n4are such as previously described for the compounds of formula I and A2=C1-6-alkyl or aryl-C1-6-alkyl and A4=halogen or OTf, d=0 or 1, R99=suitable protective group such as benzyl or trityl.

When a normal connection is obtained XVII, a compound of formula VIII is first treated with a suitable organolithium reagent or a metal catalyst followed by reaction with a compound of formula XIX in a suitable solvent. Suitable solvents for use in the above method included such ethers, like tetrahydrofuran (THF), glyme, diethyl ether, dioxane and the like, aromatic hydrocarbons such as benzene or toluene, is not limited to these solvents. Suitable varieties orginality and metal for use in this method include compounds orginality, such as n-butyl lithium or tert-butyl lithium; magnesium, not limited to the above is exectly. The above method is carried out at temperatures between about -78°C and 70°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Mainly used equimolar amounts of reactants, although if necessary, used a higher or lower number. The compounds of formula VIII and XIX were usually commercial drugs or received by known methods. For example, the compounds of formula XIX received by the ways presented in figure 6b, the result of substitution of the compounds of formula VIII compound of formula XVI.

Optically pure isomers, the compounds of formula I' and I", was received, as shown in figure 19 from (±)-SYN-isomer, compounds of formula (±)-I-sin:

SCHEME 19

where X, R1, R2, R3, G1, (CR4aR5a)n1, (Z)n2, (CR4bR5b)n3, R6a, R6band (Q1)n4are as previously described for the compounds of formula I.

When usual obtain optically separated SYN-compounds of formulas I' and I" (±)-SYN-compound of formula I is subjected to liquid chromatography using a chiral column or applied the method of diastereomerism, using optically active acid or optically active base. When the desired enantiomers of formulae I' and I" received in their respective diastereomeric salt form (compounds of formula I-(HA6)n7) by way of the diastereomeric salts (where HA6=optically pure acid, such as tartaric or mandelic acid), the enantiomers of the formula I' and I" received in their respective free forms by neutralizing the reaction mixture. Additionally, the compounds of formula I' and I" in the form of diastereoisomeric salts was treated with HCl under suitable conditions so as to obtain the compounds of formula I-(HA6)n7where n7=2, and HA6=HCl.

Optically pure isomers, the compounds of formula I' and I"," received, as shown in figure 20, from (±)-anti-compound of formula I:

SCHEME 20

where X, R1, R2, R3, G1, (CR4aR5a)n1, (Z)n2, (CR4bR5b)n3, R6a, R6band (Q1)n4are as previously described for the compounds of formula I.

When usual obtain optically separated anti-compounds of formulas I' and I"" (±)-anti-compound of formula I is subjected to liquid chromatography using a chiral column or applied the method of the diastereomeric salts using an optically active acid or optically active about the article. When the desired enantiomers of formulae I' and I" received in their respective diastereomeric salt form (compounds of formula I-(HA6)n7) by way of the diastereomeric salts (where HA6=optically pure acid, such as tartaric or mandelic acid), the enantiomers of the formula I' and I" received in their respective free forms by neutralizing the reaction mixture. Additionally, the compounds of formula I' and I"in the form of diastereoisomeric salts was treated with HCl under suitable conditions so as to obtain the compounds of formula I-(HA6)n7where n7=2, and HA6=HCl.

Optically pure isomers, the compounds of formula III' and III", was received, as shown in figure 21, from (±)-compound of formula III:

SCHEME 21

where R2, R3, (Z)n2, (CR4bR5b)n3and (Q1)n4are as previously described for the compounds of formula I, and G1=NR72R82.

When usual obtain optically separated compounds of the formula III' and III" (±)-compound of formula III were subjected to liquid chromatography using a chiral column or applied the method of the diastereomeric salts using an optically active acid. When the desired enantiomers of formula III' and III" received in their respective diastereomeric salt form, connect the Oia formula III' and III" received in their respective free nesolenyh forms by neutralizing the reaction mixture, followed by extraction with a suitable organic solvent, such as EtOAc or methylene chloride.

Optically pure isomers, the compounds of formula II' and II", prepared as shown in scheme 22, of (±)-SYN-compound of formula II.

SCHEME 22

where R2, R3, (Z)n2, (CR4bR5b)n3and (Q1)n4are as previously described for the compounds of formula I, and G1=NR72R82.

When usual obtain optically separated SYN-compounds of formula II' and II" (±)-SYN-compound of formula II were subjected to liquid chromatography using a chiral column or applied the method of the diastereomeric salts using an optically active acid or optically active base. When the desired enantiomers of formula II' and II" received in their respective diastereomeric salt form (compounds of formula I-HA6by way of diastereoisomeric salts, where HA6=optically pure acid, such as tartaric or mandelic acid), the enantiomers of formula II' and II" received in their respective free forms by neutralizing the reaction mixture.

Optically pure isomers, the compounds of formula II' and II", prepared as shown in scheme 23, of (±)-anti-compound of formula II.

SCHEME 23

where R23, (Z)n2, (CR4bR5b)n3and (Q1)n4are as previously described for the compounds of formula I, and G1=NR72R82.

When usual obtain optically separated anti-compounds of formula II' and II"" (±)-anti-compound of formula II were subjected to liquid chromatography using a chiral column or applied the method of the diastereomeric salts using an optically active acid or optically active base. When the desired enantiomers of formula II' and II" received in their respective diastereomeric salt form (compounds of formula I-HA6by way of diastereoisomeric salts, where HA6=optically pure acid, such as tartaric or mandelic acid), the enantiomers of formula II' and II" received in their respective free forms by neutralizing the reaction mixture.

The compounds of formula II', II", II' and II" of the present invention and the intermediates used in the synthesis of compounds of the present invention, obtained according to the method of G, as shown below in schemes 24-27. Optically pure compound of formula II' received, as shown in figure 24 of the optically pure compounds of formula IIa':

The WAY G:

SCHEME 24

where R2, R3, (Z)n2, (CR4bR5b)n3and (Q1)n4are such as OPI is ANO previously for compounds of formula I; G1=NR72R82and Z55=chiral auxiliary substance.

When usual obtain the compounds of formula II' compound of formula IIa' (for which OZ55taken together with equal O-(C=O)-R*in which R*is a chiral auxiliary substance) was introduced into the reaction under conventional reaction conditions for hydrolysis of ester to alcohol. Conventional hydrolysis conditions include HCl in water or NaOH, KOH or LiOH in water. Suitable solvents include water, THF, acetonitrile or an alcohol, such as methanol or ethanol. The above method is performed at temperatures between about -5°C and 100°C. the Above-mentioned method of producing compounds of this invention conducted at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Mainly used equimolar amounts of reactants, however, if necessary, used the excess of HCl or NaOH.

Optically pure compound of formula II was obtained as shown in scheme 25, from optically pure compound of formula IIa":

SCHEME 25

where R2, R3, (Z)n2, (CR4bR5b)n3and (Q1)n4are as previously described for the compounds of formula I; G1=NR72R82and Z55=airlinesmalaysia substance.

When usual obtain the compounds of formula II, a compound of formula IIa" (for which OZ55taken together with equal O-(C=O)-R*in which R*is a chiral auxiliary substance) was introduced into the reaction under conventional reaction conditions for hydrolysis of ester to alcohol. Conventional hydrolysis conditions include HCl in water or NaOH, KOH or LiOH in water. Suitable solvents include water, THF, acetonitrile or an alcohol, such as methanol or ethanol. The above method is performed at temperatures between about -5°C and 100°C. the Above-mentioned method of producing compounds of this invention conducted at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Mainly used equimolar amounts of reactants, however, if necessary, used the excess of HCl or NaOH.

Optically pure compound of formula II' received, as shown in figure 26, from optically pure compounds of formula IIb':

SCHEME 26

where R2, R3, (Z)n2, (CR4bR5b)n3and (Q1)n4are as previously described for the compounds of formula I; G1=NR72R82and Z55=chiral auxiliary substance.

When the usual p is the receiving of the compounds of formula II' compound of formula IIb' (for which OZ 55taken together with equal O-(C=O)-R*in which R*is a chiral auxiliary substance) was introduced into the reaction under conventional reaction conditions to carry out the hydrolysis of ester to alcohol. Conventional hydrolysis conditions include HCl in water or NaOH, KOH or LiOH in water. Suitable solvents include water, THF, acetonitrile or an alcohol, such as methanol or ethanol. The above method is performed at temperatures between about -5°C and 100°C. the Above-mentioned method of producing compounds of this invention conducted at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Mainly used equimolar amounts of reactants, however, if necessary, used the excess of HCl or NaOH.

Optically pure compound of formula II was obtained, as shown in figure 27, from the optically pure compounds of formula IIb":

SCHEME 27

where R2, R3, (Z)n2, (CR4bR5b)n3and (Q1)n4are as previously described for the compounds of formula I; G1=NR72R82and Z55=chiral auxiliary substance.

When usual obtain the compounds of formula II, the compound of formula IIb" (for which OZ55taken together with equal O-(C=O)-R*in what oterom R *is a chiral auxiliary substance) was introduced into the reaction under conventional reaction conditions to carry out the hydrolysis of ester to alcohol. Conventional hydrolysis conditions include HCl in water or NaOH, KOH or LiOH in water. Suitable solvents include water, THF, acetonitrile or an alcohol, such as methanol or ethanol. The above method is performed at temperatures between about -5°C and 100°C. the Above-mentioned method of producing compounds of this invention conducted at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Mainly used equimolar amounts of reactants, however, if necessary, used the excess of HCl or NaOH.

Optically pure compounds of formula IIa' and IIa was obtained, as shown in figure 28, when the transformation of (±)-SYN-compound of formula II in diastereomeric the compounds of formula IIa' and IIa respectively:

SCHEME 28

where R2, R3, (Z)n2, (CR4bR5b)n3and (Q1)n4are as previously described for the compounds of formula I; G1=NR72R82and Z55=chiral auxiliary substance.

Under normal receiving diastereomers divided SYN-compounds of formula IIa' and IIa" (±)-SYN-compound of formula II vzaimode who was istawaa with chiral auxiliary substance, then the corresponding diastereomers of compounds of formula IIa' and IIa", separated by known methods, such as recrystallization or chromatography. A typical reaction consisted of the processing of (±)-SYN-compound of formula II with a suitable chiral auxiliary substance, which contain carboxylic acid or a fragment of a carboxylic acid. Treatment of (±)-SYN-compound of formula II is based on the acid chiral auxiliary substance included the usual conditions for the conversion of alcohol to ester. These conditions interact, without limitation, include DCC or EDC with a suitable catalyst, such as DMAP, HOAT or HOBT in an appropriate solvent in the presence of an appropriate base, such as triethylamine or Diisopropylamine. Treatment of (±)-SYN-compound of formula II is based on the acid chloride acid chiral auxiliary substance included the usual conditions for the conversion of alcohol in the ester with an acid chloride, such as an inert solvent and base. Typical chiral excipients include, respectively, a protected amino, such as N-(tert-butoxycarbonyl)-L-Proline, N-(tert-butoxycarbonyl)-D-Proline, (R)-(+)-α-methoxy-α-(trifluoromethyl)-phenylacetic acid, (S)-(-)-α-methoxy-α-(trifluoromethyl)-phenylacetic acid, (R)-(+)-α-methoxy-α-(trif ormetal)-phenylacetylene, (S)-(-)-α-methoxy-α-(trifluoromethyl)-phenylacetylene, (1R)-(+)-Campanula acid, (1S)-(-)-Campanula acid and (1S)-(-)-acid chloride campanulas acid, not limited to these substances. Suitable solvents for use in both above-mentioned methods include ethers, like tetrahydrofuran (THF), glyme, and the like; dimethylformamide, dimethyl sulfoxide; halogenated solvents such as methylene chloride or chloroform, is not limited to the above solvents. The above method is performed at temperatures between about -5°C and 100°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Basically, if necessary, used equimolar amounts of reactants.

Optically pure compounds of formula IIb' and IIb ' was received, as shown in figure 29, when the transformation of (±)-anti-compound of formula II in diastereomeric the compounds of formula IIb' and IIb respectively:

SCHEME 29

where R2, R3, (Z)n2, (CR4bR5b)n3and (Q1)n4are as previously described for the compounds of formula I; G1=NR72R82and Z55=chiral su is magadelene substance.

Under normal receiving diastereomers divided anti-compounds of formula IIb' and IIb" (±)-anti-compound of formula II interacted with chiral auxiliary substance, and then the corresponding diastereomers of compounds of formula IIb' and IIb", separated by known methods, such as recrystallization or chromatography. A typical reaction consisted of the processing of (±)-anti-compound of formula II with a suitable chiral auxiliary substance, which contain carboxylic acid or a fragment of a carboxylic acid. Treatment of (±)-anti-compound of formula II is based on the acid chiral auxiliary substance included the usual conditions for the conversion of alcohol to ester. These interaction terms were included DCC or EDC with a suitable catalyst, such as DMAP, HOAT or HOBT in an appropriate solvent in the presence of an appropriate base, such as triethylamine or Diisopropylamine. Treatment of (±)-anti-compound of formula II is based on the acid chloride acid chiral auxiliary substance included the usual conditions for the conversion of alcohol in the ester with an acid chloride, such as an inert solvent and base. Typical chiral excipients include, respectively, a protected amino, such as N-(tert-butoxycarbonyl)-L-Proline, N-(Tr is t-butoxycarbonyl)-D-Proline, (R)-(+)-α-methoxy-α-(trifluoromethyl)-phenylacetic acid, (S)-(-)-α-methoxy-α-(trifluoromethyl)-phenylacetic acid, (R)-(+)-α-methoxy-α-(trifluoromethyl)-phenylacetylene, (S)-(-)-α-methoxy-α-(trifluoromethyl)-phenylacetylene, (1R)-(+)-Campanula acid, (1S)-(-)-Campanula acid and (1S)-(-)-acid chloride campanulas acid, not limited to these substances. Suitable solvents for use in both above-mentioned methods include ethers such as tetrahydrofuran (THF), glyme, and the like; dimethylformamide, dimethyl sulfoxide; halogenated solvents such as methylene chloride or chloroform, is not limited to the above solvents. The above method is performed at temperatures between about -5°C and 100°C. the Above-mentioned method of producing compounds of the present invention is preferably carried out at approximately atmospheric pressure, although if necessary, used a higher or lower pressure. Basically, if necessary, used equimolar amounts of reactants.

The following examples are intended to illustrate and not limit the present invention.

Conditions analytical HPLC:

[318] Unless otherwise indicated, all HPLC analyses were performed on a Micromass system with column XTERRA MS C18 5 MK 4,6h50 mm and with detection at 254 nm. The table below shows the received data relative to the mobile phase, velocity and pressure.

Table a
Time (min)%CH3CN0,01% HCOOH in H2O %For (ml/min)Pressure (lb/inch)
0,005951,3400
4,0010001,3400
5,5010001,3400
6,005951,3400
7,005951,3400

Conditions prepreparation HPLC:

[319] In the case where it is stated that "it was purified by HPLC on Gilson"interest compounds were purified using the working device for preparative/polypr paratively HPLC on Gilson with column Phenomenex Luna 5 micron C18 (2) h 20MM MK and liquid manipulator Gilson 215 (manometric module 806, dynamic mixer C, detection at 254 nm). In the table In the gradient, velocity, time, and pressure.

Table
Time (min)%CH3CN0,01% HCOOH in H2O %For (ml/min)Pressure (lb/inch)
0,00595151000
15,006040151000
15,101000151000
19,001000151000
20,00595151000

Intermediate a-1 (compound of formula VI, in which R2=CH3, R3=H, G1=N(CH3)2and A2=CH 3): A solution of 2-iodine-1-(6-methoxy-naphthalene-2-yl)-propane-1-she (compound of formula VII, in which R2=CH3, R3=H, A3=I and A2=CH3) (54 g, 161 mmol), dimethylamine (161 ml of 2M solution in MeOH, 322 mmol) and Diisopropylamine (28 ml, 161 mmol) in 500 ml of CHCl3and 500 ml of MeOH was stirred at room temperature for 16 hours. The reaction mixture was concentrated in vacuum and distributed between Na2CO3(feast upon.) and CH2Cl2. The aqueous phase was extracted with CH2Cl2(4×), dried over Na2SO4and concentrated in vacuum. Intermediate a-1 was considered to be pure according to the1H-NMR and used directly in the next reaction.1H-NMR (CDCl3, 200 MHz) d is 1.31 (d, 3H,J=7,0 Hz)to 2.35 (s, 6H), of 3.94 (s, 3H), of 4.16 (q, 1H,J=8.0 Hz), 7,15-8,56 (m, 6H); MS (ES 258,0 (M+1).

Intermediate a-2 (compound of formula VI, in which R2=CH3, R3=H and G1=N(CH3)2: 2-Liter round bottom flask, equipped with a partial condenser hot irrigation, downloaded the intermediate a-1 (38 g, 148 mmol), 48% HBraq.(800 ml) and glacial acetic acid and heated in an oil bath at 120°C with stirring for 16 hours. The reaction mixture was concentrated in vacuo to small volume, as far as possible, cooled in a bath with ice and extinguished 8M NaOH. The cooled suspension was then extracted CHsub> 2Cl2(7×). The organic layers were combined and filtered through a loose layer of celite. The filtrate was concentrated in vacuum and the product was further purified by the method of column chromatography on silica gel (gradient from 5% CH3HE:CH2Cl2c 1% Et3N per 100 ml of solvent up to 10% of CH3HE:CH2Cl2c 1% Et3N per 100 ml solvent)to obtain the desired intermediate a-2 in the form of a foamed solid brown color.1H-NMR (CDCl3, 200 MHz) d of 1.34 (d, 3H,J=8.0 Hz), 2,39 (s, 6H), 4,22 (kV, 1H,J=8.0 Hz), 7,09-7,13 (m, 2H), 7,66 (d, 1H,J=8.0 Hz), 7,82 (d, 1H,J=8.0 Hz), 8,02 (DD, 1H,J=2,0, 10,0 Hz), charged 8.52 (d, 1H,J=2,0 Hz).

Intermediate a-3 (a compound of the formula VI, in which R2=CH3, R3=CH3, A2=CH3and G1=N(CH3)2: A solution of 2-bromo-6-methoxynaphthalene (2.37 g, 10 mmol) in THF (30 ml) at -78°C was downloaded tBuLi (1.7 M, 11,76 ml, 20 mmol) in 20 minutes. The reaction mixture was stirred at -78°C for 20 minutes, the time within which added net 2-dimethylamino-2-methylpropionitrile (1,23 g, 11.1 mmol). The mixture was left to stir for an additional 30 minutes and then left to warm to room temperature. To the mixture was added 2 N. H2SO4(50 ml) and was stirred for 10 minutes. The THF layer was separated and the aqueous layer was extracted with ethyl acetate (2 × 40 ml). The water layer under elatively, using 2 n NaOH to pH 8.0 and extracted with CH2Cl2(3 × 40 ml). CH2Cl2The extract was washed with water, brine, dried over anhydrous sodium sulfate and concentrated in vacuum to obtain the intermediate of a-3 as a pale yellow oil. MS (ES):m/z271,96 [M+];1H NMR (CDCl3, 400 MHz): δ which is 9.09 (d,J=1.2 Hz, 1H), 8,35 (DD,J=to 8.8, 4.0 Hz, 1H), 7,76 (l,J=8,8 Hz, 1H), 7.62mm (l,J=8,8 Hz, 1H), 7,07 (DD,J=of 8.8 and 2.8 Hz, 1H), 7,03 (l,J=2,8 Hz, 1H), 3,83 (s, 3H), of 2.21 (s, 6H), 1,25 (s, 6H).

Intermediate a-4 (compound of formula VI, in which R2=CH3, R3=CH3and G1=N(CH3)2): A mixture of intermediate a-3 (1.92 g, 7,11 mmol) and aqueous HBr (48%, 30 ml) was added glacial acetic acid (30 ml) and was heated to 120°C for 16 hours. The reaction mixture was cooled to room temperature and neutralized 2 N. NaOH (until pH 5.0) and saturated NaHCO3(up to pH 7.0). The aqueous mixture was extracted with CH2Cl2(4 × 40 ml)and the combined organic layers were washed with water, brine, dried over anhydrous sodium sulfate and concentrated in vacuo to obtain the crude product as a brown oil. Purification of the crude product by the method of column chromatography (10% MeOH/CH2Cl2) gave intermediate a-4. MS (ES):m/z258,22 [M+H+];1H NMR (CDCl3, 400 MHz) δ 9,17 (s, 1H), 8,39 (DD,J8,8, 2.0 Hz, 1H), 7,86 (l,J=8,4 Hz, 1H), 7,63 (l,J=8,8 Hz, 1H), 7,15 (s, 1H), 7,12 (DD,J=to 8.4, 2.4 Hz, 1H), to 2.29 (s, 6H), of 1.34 (s, 6H).

Intermediate A-5 (compound of formula XII in which R2=CH3, R3=H, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): Solution (160 ml) of 1-(6-hydroxynaphthalene-2-yl)-propane-1-she (10.0 g, 50.0 mmol) in THF, triphenylphosphine (20,0, 76,0 mmol) and methyl 2,2-dimethyl-3-hydroxypropionate (7,0 ml, 55,0 mmol) was pumped out the air, then placed in an atmosphere of N2, cooled in a bath of ice and portions was added DIAD (15.0 ml, 76,0 mmol) for 5 minutes. The mixture was left to warm to room temperature and then was heated to 45°C for 16 hours. The reaction mixture was concentrated in vacuo to a dark oil and was purified by the method of column chromatography on silica gel (5 to 10% EtOAc/hexane). The white solid was recrystallized from hot hexane to obtain the desired intermediate A-5.1H NMR (CDCl3, 400 MHz) δ of 1.28 (t, 3H,J=7,2 Hz), of 2.33 (s, 6H), to 1.38 (s, 6H), of 3.12 (q, 1H,J=7,2 Hz), and 3.72 (s, 3H), of 4.12 (s, 2H), 7,16 (m, 2H), 7,20 (DD, 1H,J=2,5, 8,8 Hz), 7,76 (d, 1H,J=8.6 Hz), to 7.84 (d, 1H,J=8,8 Hz), 8,01 (DD, 1H,J=to 2.0, 8.6 Hz), to 8.41 (s, 1H).

Intermediate A-6 (compound of formula XI in which R2=CH3, R3=H, n2=0, n3=1, R4band R5b=CH3, n4=1, A3=Br and Q1=CO2CH3): A round bottom flask, 250 ml, containing intermediate A-5(at 8.60 g, a 27.4 mmol) and CuBr2(12.2 g, 54,7 mmol) were loaded in dioxane (55 ml), was pumped out the air, were placed in an atmosphere of N2and was heated to 1100C for 16 hours. The reaction mixture was concentrated in vacuo to a dark suspension and purified by the method of column chromatography on silica gel (5-10% EtOAc/hexane). Not quite white solid substance was recrystallized from a mixture of hexane/EtOAc to obtain 9,36 g of intermediate A-6 in the form of not-quite-white solid.1H NMR (CDCl3, 400 MHz) δ to 1.38 (s, 6H), of 1.95 (d, 3H,J=6,6 Hz), of 3.77 (s, 3H), of 4.12 (s, 2H), 5,44 (kV, 1H,J=6,6 Hz), 7,16 (m, 2H), 7,21 (DD, 1H,J=2,4, 8,8 Hz), to 7.77 (d, 1H,J=8.0 Hz), 7,86 (d, 1H,J=8,8 Hz), 8,03 (DD, 1H,J=2,4, 8,8 Hz), 8,49 (s, 1H).

Intermediate a-7 (compound of formula XII in which R2=H, R3=H, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained according to the methods described for intermediate A-5 above except for the substitution of 1-(6-hydroxynaphthalene-2-yl)propane-1-it 1-(6-hydroxynaphthalene-2-yl)-atenonol. MS (ES) 301,0 (M+1).

Intermediate a-8 (compound of formula XI in which R2=H, R3=H, n2=0, n3=1, R4band R5b=CH3, n4=1, A3=Br and Q1=CO2CH3): Intermediate a-7 (3.0 g, of 9.99 mmol) and CuBr2(4.9 g, 21,97 mmol) was dissolved in dioxane (35 ml) and heated at 100°C for 20 hours. The crude mixture was concentrated in vacuum to allali water and was extracted with CH 2Cl2(3×). The organic layers were dried over Na2SO4, filtered and concentrated in vacuum. The crude product was purified by the method of column chromatography on silica gel (10% EtOAc:hexane)to obtain the desired product as a yellow solid.1H NMR (CDCl3, 400 MHz) δ to 1.38 (s, 6H), and 3.72 (s, 3H), of 4.12 (s, 2H), 4,56 (s, 2H), 7,17-of 7.23 (m, 2H), 7,78 (d, 1H,J=8,8 Hz), 7,86 (d, 1H,J=9,2 Hz), to 7.99 (DD, 1H,J=2,0, 6.4 Hz), 8,43 (s, 1H).

Intermediate A-9 (a compound of the formula XII in which R2=CH3, R3=H, n2=0, n3=1, R4band R5bthe carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et): The title compound was obtained according to the methods described for intermediate A-5 above except for the substitution of methyl 2,2-dimethyl-3-hydroxypropionate ethyl ester, 1-hydroxymethyl-cyclopentanecarboxylic acid.1H NMR (CDCl3, 400 MHz) δ 1,22 (t, 3H,J=8,0 Hz)of 1.28 (t, 3H,J=8.0 Hz), 1,72-to 1.82 (m, 6H), 2,19-2,22 (m, 2H), 3,11 (q, 2H,J=8.0 Hz), 4,18 (m, 4H), 7,16-7,21 (m, 2H), of 7.75 (d, 1H,J=8,8 Hz), 7,83 (d, 1H,J=8,8 Hz), 8,00 (DD, 1H,J=2,0, 6.4 Hz), 8,40 (s, 1H).

Intermediate A-10 (a compound of the formula XI in which R2=CH3, R3=H, n2=0, n3=1, R4band R5bthe carbon to which they were attached, form a ring cyclopentyl, n4=1, A3=Br and Q1=CO2Et): The title compound was obtained according to the methods described above for intermediate A-6 except for the substitution of intermediate 5 intermediate A-9. 1H NMR (CDCl3, 400 MHz) δ 1,22 (t, 3H,J=8.0 Hz), 1,72 is 1.75 (m, 6H), of 1.95 (d, 3H,J=6,4 Hz), 2,19-of 2.23 (m, 2H), 4,18 (q, 2H,J=8.0 Hz), 5,44 (kV, 1H,J=6,4 Hz), 7,11-7,21 (m, 2H), to 7.77 (d, 1H,J=8,8 Hz), the 7.85 (d, 1H,J=8,8 Hz), 8,03 (DD, 1H,J=2,0, 6.4 Hz), 8,48 (s, 1H).

Intermediate A-11 (compound of formula VII, in which R2=CH2CH3, R3=H, A3=Cl, A2=CH3): The title compound was prepared as follows: 1-Liter triggerlevel round bottom flask fitted with a valve for N2and partial condenser hot irrigation, downloaded shavings Mg (of 7.70 g, 317 mmol) and dry THF (300 Il). 6-Bromo-2-methoxy-naphthalene (compound of formula VIII, in which A4=Br and A2=CH3) (60,0 g, 253 mmol) was added in portions over a period of 20 minutes. From the reaction mixture was pumped out the air, were placed in an atmosphere of N2and heated gradually to 50°C for 1 hour. In another triggerlevel round bottom flask fitted with a valve for N2, addition funnel and membrane were placed 2-chlorobutyrate (compound of formula IX in which R2=CH2CH3, R3=H, A3=Cl, A5=Cl) (64,0 g, 505 mmol) and dry THF (70 ml). The reaction mixture was cooled to -50°C., and the Grignard reagent, prepared previously, was transferred to a cannula with a dropping funnel under pressure N2. Then, the Grignard reagent was added dropwise within 30 minutes. The reaction is th the mixture was left to warm to room temperature (CT) and was stirred for 16 hours. In the reaction mixture were loaded with 5% HCl, the volume of THF was reduced in vacuo and added water and the product was extracted with CH2Cl2(3×). The combined organic layers were washed with water, saturated salt solution, dried over MgSO4and concentrated in vacuum. The crude solid was purified by chromatography on silica gel (9:1 EtOAc:hexane) and recrystallized from MeOH to obtain specified in the title compound.1H NMR (CDCl3, 400 MHz) δ is 1.11 (t, 3H,J=7,2 Hz), 2,04-of 2.15 (m, 1H), 2,18-to 2.29 (m, 1H), 3,93 (s, 3H), 5,18 with 5.22 (m, 1H), 7,16 (d, 1H,J=the 2.4 Hz), 7,22 (DD, 1H,J=6,0, 8,8 Hz), 7,79 (d, 1H,J=8,8 Hz), 7,87 (d, 1H,J=8,8 Hz), 8,02 (DD, 1H,J=1,6, 8,8 Hz), 8,46 (s, 1H).

Intermediate A-12 (a compound of the formula VI, in which R2=CH2CH3, R3=H, G1=N(CH3)2and A2=CH3) was obtained by the methods described for intermediate A-1 above except for the substitution of 2-iodine-1-(6-methoxy-naphthalene-2-yl)-propane-1-it-intermediate A-11. MS (ES) 271,7 (M+1),1H NMR (CDCl3, 400 MHz) δ of 0.89 (t, 3H,J=the 7.4 Hz), 1,72-of 1.84 (m, 1H), 1.91 a-2,02 (m, 1H), of 2.38 (s, 6H), of 3.96 (s, 3H), 3,99-a 4.03 (m, 1H), 7,15-7,21 (m, 2H), to 7.77 (d, 1H,J=9.0 Hz), 7,87 (d, 1H,J=9.0 Hz), 8,07 (DD, 1H,J=the 1.8 and 9.6 Hz), 8,53 (s, 1H).

Intermediate A-13 (a compound of the formula IV in which R2=CH2CH3, R3=H, G1=N(CH3)2) was obtained by the methods described for intermediate A-2 above except for the substitution of interme the IATA And-1 intermediate A-12. MS (ES) 258,3 (M+1).

According to the General methods described previously, received the following intermediates of formula III, which are shown in table 1.

Table 1
The list of intermediates of formula III
The ofR2R3G1n2Zn3R4bR5bn4Q1
1-1CH3HN(CH3)20-1CH3CH31CO2CH3
1-2CH3HN(CH3)214 Ph0 --1CO2CH3
1-3CH3HN(CH3)213 Ph0--1CO2CH3
1-4CH3HN(CH3)214 Ph1HH1CO2CH3
1-5CH3HN(CH3)20-1CH3CH31CH3
1-6CH3HN(CH )214 Ph0--1OtBu
1-7CH3HN(CH3)214 PhO1HH1CO2CH3
1-8CH3HN(CH3)20-2HH1OCH3
1-9CH3HN(CH3)214 Ph0--1OCH3
1-10 CH3HN(CH3)21TRANS
CH=CHPh
0--0-
1-11CH3HN(CH3)214 Ph0--1CN
1-12CH3HN(CH3)214 Ph0--1NO2
1-13CH3HN(CH3)20-1EtEt1 CO2Et
1-14CH3HN(CH3)20-1CH2CH2ring1CO2Et
1-15CH3HN(CH3)20-1CH2CH2CH2ring1CO2Et
1-16CH3HN(CH3)20-1CH2CH2OCH2CH2ring1CO2Et
1-17CH3HN(CH3)201CH2(CH2)3CH2ring1CO2CH3
1-18CH3HN(CH3)20-1CH2(CH2)2CH2ring1CO2Et
1-19CH3HN(CH3)21Ph0--0-
1-20CH3HN(CH2)2O(CH2)2ring0-1CH3CH31CO2CH3
1-21CH3HN(Et)20-1CH3CH31CO2CH3
1-22CH3HN(CH3)cyclohexyl0-1CH3CH31CO2CH3
1-23CH3HN(CH3)n-butyl0-1CH3CH31CO2CH3
1-24CH3HN(CH3)iPr0- 1CH3CH31CO2CH3
1-25CH3HN(CH3)Ph0-1CH3CH31CO2CH3
1-26CH3HN(CH2)40-1CH3CH31CO2CH3
1-27CH3CH3N(CH3)20-1CH3CH31CO2CH3
1-28 CH3HN(CH3)Et0-1CH3CH31CO2CH3
1-29CH3HN(CH3)20-0--1CO2tBu
1-30A*1Ph0--0-
1-31EtHN(CH3)20-1CH3CH31CO2CH3
1-32CH3HN(CH3)iPr0-1CH2(CH2)2CH2ring1CO2Et

in which A*=R2R3G1taken together with the carbon atom to which they attached, form:

where • is a carbon to which they attach.

Method And General synthesis for the preparation of compounds of formula III: From THF solution (0.4 M) of compounds of formula IV (1 EQ.) (intermediate a-2, a-4 or A-13), triphenylphosphine (1.1 EQ.) and the compounds of formula V (1 EQ.) was sucked out the air, and the mixture was placed in an atmosphere of N2, cooled in a bath of ice and portions was added DIAD (1 EQ.) within 5 minutes. The mixture was left to warm to room temperature and then was heated to 45°C for 16 hours. The reaction mixture was concentrated in vacuum and purified by the method of column chromatography on silica gel (gradient from 6:1 CH2Cl2:10% CH3OH in CH2Cl2(1% Et3N) to 3:1 CH2Cl2:10% CH3OH in CH2Cl2(1% Et3N).

The method In General synthesis for the preparation of compounds of formula III: acetone relevy solution (0.5 M) of the compounds of formula XI (1 EQ.) (intermediate a-8 or A-10) was added 1 equivalent of NaI and 3 equivalent HG 1and the mixture was left for stirring at 40°C for 16 hours. The reaction mixture was concentrated in vacuo to suspension and distributed between CH2Cl2and NaHCO3(feast upon.), and the aqueous layer was extracted with CH2Cl2(5×). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuum. The obtained residue was purified by chromatography on silica gel (gradient from 6:1 CH2Cl2:10% CH3OH in CH2Cl2(1% Et3N) to 3:1 CH2Cl2:10% CH3OH in CH2Cl2(1% Et3N)to obtain the desired compound of formula III.

COMPOUND 1-1 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method And conventional synthesis, was used a compound of the formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) d of 1.18 and 1.35 (m, 9H), 3,68 (s, 3H), 4,10 (s, 1H), 7,14-7,20 (m, 2H), 7,74 (d, 1H,J=8.0 Hz), to 7.84 (d, 1H,J=8.0 Hz), 7,74 (DD, 1H,Jor =0.6, 4.4 Hz), 8,55 (s, 1H).

COMPOUND 1-2 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)21=CO2CH3): The title compound was obtained by the above method And the total synthesis was used a compound of the formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ of 1.30 (d, 3H,J=6,0 Hz), of 2.33 (s, 6H), 3,91 (s, 3H), 4,15 (kV, 1H,J=6,0 Hz), at 5.27 (s, 2H), 7,20-7,31 (m, 1H), 7,56 (d, 2H,J=8.0 Hz), 7,74 (d, 1H,J=8,4 Hz), 7,89 (d, 1H,J=8,8 Hz), 8,06-8,10 (m, 4H), to 8.57 (s, 1H); MS (ES) 391,9 (M+1).

COMPOUND 1-3 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=3-phenyl, n3=0, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method And the total synthesis, which used the compound of formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=1, Z=3-phenyl, n3=0, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ 1.32 to (d, 3H,J=7,0 Hz), a 2.36 (s, 6H), of 3.94 (s, 3H), 4,18 (kV, 1H,J=6,6 Hz in), 5.25 (s, 2H), 7,20-7,31 (m, 1H), 7,44-7,52 (m, 2H), 7.68 per for 7.78 (m, 2H), 7,89 (d, 1H,J=10.0 Hz), 8,00-of 8.09 (m, 2H), 8,18 (s, 1H), 8,56 (s, 1H); MS (ES) 392,0 (M+1).

COMPOUND 1-4 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=1, R4band R5b=H, n4=1, and Q1=CO2CH3): The criminal code is mentioned in the title compound was obtained by the above method And the total synthesis when used, the compound of formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=1, Z=4-phenyl, n3=1, R4band R5b=H, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ of 1.30 (d, 3H,J=8.0 Hz), to 2.35 (s, 6H), to 3.64 (s, 2H), 3,68 (s, 3H), 4,17 (kV, 1H,J=8.0 Hz), 5,16 (s, 2H), 7,11-8,08 (m, 9H), 8,56 (s, 1H); MS (ES) 405,9 (M+1).

COMPOUND 1-5 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CH3): The title compound was obtained by the above method And the total synthesis was used a compound of the formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CH3.1H NMR (CDCl3, 200 MHz) δ of 1.07 (s, 9H), of 1.40 (d, 3H,J=6.2 Hz), is 2.37 (s, 6H), to 3.73 (s, 2H), 4,20 (kV, 1H,J=7,0 Hz), 7,11 (d, 1H,J=2.2 Hz), 7,20 (DD, 1H,J=2,6, 9,2 Hz), 7,47-7,58 (m, 1H), to 7.84 (d, 1H,J=8,8 Hz), 7,88 (DD, 1H,J=1,4, and 8.2 Hz), 8,55 (s, 1H).

COMPOUND 1-6 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=OtBu): The title compound was obtained by the above method And the total synthesis, which used the compound of formula IV, R2=CH3, R3=H and G1=N(CH 3)2and the compound of formula V, A1=OH, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=OtBu.1H NMR (CDCl3, 200 MHz) δ 1.30 and of 1.36 (m, 12H), to 2.35 (s, 6H), 4,17 (kV, 1H,J=6,0 Hz), 5,14 (s, 2H), 7,01-7,07 (m, 2H), 7.24 to 7,30 (m, 2H), was 7.36-7,41 (m, 2H), 7,73-of 7.90 (m, 2H), 8,05-8,10 (m, 1H), 8,58 (s, 1H); MS (ES) 406,0 (M+1).

COMPOUND 1-7 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-PhO, n3=1, R4band R5b=H, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method And the total synthesis was used a compound of the formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=1, Z=4-PhO, n3=1, R4band R5b=H, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) d is 1.31 (d, 3H,J=6,0 Hz), was 2.34 (s, 6H), of 3.80 (s, 3H), 4,17 (kV, 1H,J=6,0 Hz), of 4.66 (s, 2H), 5,13 (s, 2H), 6,92-6,98 (m, 2H), 7.23 percent-7,44 (m, 4H), 7,72-8,10 (m, 3H), to 8.57 (s, 1H); MS (ES 422,0 (M+1).

CONNECTION 1-8 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=2, R4band R5b=H, n4=1, and Q1=OCH3): The title compound was obtained by the above method And the total synthesis was used a compound of the formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=0, n3=2, R4band R5b=H, n4=1, and Q1=OCH3. MS (ES) 302,3 (M+1).

The CONNECTION IS GIVING 1-9 (Compound of formula III, in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=OCH3): The title compound was obtained by the above method And the total synthesis, they took the compound of formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=OCH3. MS (ES) 364,3 (M+1).

COMPOUND 1-10 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z corresponds to TRANS-CH=CHPh, n3 and n4=0): is Specified in the title compound was obtained by the above method And the total synthesis was used a compound of the formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=1, Z corresponds to TRANS-CH=CHPh, n3 and n4=0. MS (ES) 360,3 (M+1).

COMPOUND 1-11 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=CN): The title compound was obtained by the above method And the total synthesis was used a compound of the formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=CN. MS (ES) 359,3 (M+1).

COMPOUND 1-12 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-Fe is Il, n3=0, n4=1, and Q1=NO2): The title compound was obtained by the above method And the total synthesis was used a compound of the formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=NO2. MS (ES) 381,3 (M+1).

CONNECTION 1-13 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH2CH3, n4=1, and Q1=CO2Et): The title compound was obtained by the above method And the total synthesis was used a compound of the formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=0, n3=1, R4band R5b=CH2CH3, n4=1, and Q1=CO2Et. MS (ES) 400,3 (M+1).

CONNECTION 1-14 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopropyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above method And the total synthesis, which used the compound of formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=0, n3=1, R4band R5btaken together with the carbon to which which they were attached, make ring cyclopropyl, n4=1, and Q1=CO2Et. MS (ES) 370,3 (M+1).

CONNECTION 1-15 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclobutyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above method And the total synthesis was used a compound of the formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclobutyl, n4=1, and Q1=CO2Et. MS (ES) 384,3 (M+1).

COMPOUND 1-16 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring of 4-pyranyl, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method And the total synthesis was used a compound of the formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring of 4-pyranyl, n4=1, and Q1=CO2CH3. MS (ES 400,3 (M+1).

CONNECTION 1-17 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a cyclohexyl ring, n4=1, and Q1=CO2Et): The title compound was obtained by the above method And the total synthesis, which used the compound of formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a cyclohexyl ring, n4=1, and Q1=CO2Et. MC (ES) 412,3 (M+1).

CONNECTION 1-18 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above method And the total synthesis, which used the compound of formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et. MC (ES) 398,2 (M+1).

CONNECTION 1-19 (Compound of formula III in which R2=CH3,R 3=H, G1=N(CH3)2, n2=1, Z=Ph, n3 and n4=0): is Specified in the title compound was obtained by the above method And the total synthesis, which used the compound of formula IV, R2=CH3, R3=H and G1=N(CH3)2and the compound of formula V, A1=OH, n2=1, Z=Ph, n3 and n4=0.1H NMR (CDCl3, 200 MHz) δ 1.32 to (d, 3H,J=6,0 Hz), is 2.37 (s, 6H), is 4.21 (q, 1H,J=6,0 Hz), of 5.50 (s, 2H), 7.24 to to 7.50 (m, 3H), of 7.75 (d, 2H,J=10.0 Hz), 7,88 (d, 2H,J=8.0 Hz ), 8,04-of 8.09 (m, 2H), 8,58 (s, 2H); MS (ES 334,2 (M+1).

CONNECTION 1-20 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH2)2O(CH2)2-ring, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method B total synthesis, which used the compound of formula XI, R2=CH3, R3=H, A3=Br, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3and HG1=HN(CH2)2O(CH2)2. MC (ES) 400,2 (M+1).

CONNECTION 1-21 (Compound of formula III in which R2=CH3, R3=H, G1=N(Et)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method B total synthesis, which used the compound of formula XI, R2=CH3, R3=H, A3=Br, n2=0, n3=1, R4b and R5b=CH3, n4=1, and Q1=CO2CH3and HG1=HN(Et)2. MC (ES) 386,2 (M+1).

CONNECTION 1-22 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)-cyclohexyl, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method B total synthesis, which used the compound of formula XI, R2=CH3, R3=H, A3=Br, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3and HG1=HN(CH3)-cyclohexyl. MC (ES) TO 426.2 (M+1).

CONNECTION 1-23 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)-n-butyl, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method B total synthesis, which used the compound of formula XI in which R2=CH3, R3=H, A3=Br, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3and HG1=HN(CH3)-n-butyl. MC (ES) 400,2 (M+1).

CONNECTION 1-24 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)iPr, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method B total synthesis, which is used to connect the group of the formula XI, R2=CH3, R3=H, A3=Br, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3and HG1=HN(CH3)iPr. MC (ES) 386,3 (M+1).

CONNECTION 1-25 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)Ph, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method B total synthesis, which used the compound of formula XI, R2=CH3, R3=H, A3=Br, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3and HG1=HN(CH3)Ph. MC (ES) 420,2 (M+1).

CONNECTION 1-26 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH2)4, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method B total synthesis, which used the compound of formula XI, R2=CH3, R3=H, A3=Br, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3and HG1=HN(CH2)4. MC (ES) 384,3 (M+1).

CONNECTION 1-27 (Compound of formula III in which R2=CH3, R3=CH3, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method obsessives, where used, the compound of formula IV, R2=CH3, R3=CH3and G1=N(CH3)2and the compound of formula V, A1=OH, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ is 1.31 (d, 6H,J=7,6 Hz)to 1.37 (s, 6H), to 2.29 (s, 6H), 3,70 (s, 3H), 4,10 (s, 2H), 7,12-7,26 (m, 2H), 7,68 (d, 1H,J=8,8 Hz), 7,83 (d, 1H,J=8,8 Hz), to 8.41 (DD, 1H,J=2,0, 8,8 Hz), 9,14 (s, 1H).

CONNECTION 1-28 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)Et, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method A total synthesis, which used the compound of formula IV, R2=CH3, R3=H, and G1=N(CH3)Et, and the compound of formula V, A1=OH, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3. MS (ES) 372,2 (M+1).

CONNECTION 1-29 (Compound of formula III in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, n4=1, and Q1=CO2tBu): The title compound was prepared as follows: N,N-dimethylformamide solution (25 ml) of intermediate a-2 (3.00 g, of 12.33 mmol) were loaded tert-piperonyl potassium (1.52 g, 13.56 mmol) and left to stir at room temperature for 30 minutes. Tert-butyl-bromoacetate (2.64 g, 13.56 mmol), the compound of formula V, in which A 1=Br, n2=0, n3=0, n4=1, and Q1=CO2tBu was added dropwise and left to stir for 24 hours. The mixture was dissolved in EtOAc, washed with Na2CO3(feast upon.) 2×with water 2×, and saturated saline 1×. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo to a brown oil. Column chromatography on silica gel (gradient of CH2Cl2up to 5% CH3OH:CH2Cl2(containing 1 ml Et3N/100 ml solvent) gave the desired product as a brown oil.1H NMR (CDCl3, 200 MHz) δ 1.32 to (d, 3H,J=6,0 Hz)of 1.50 (s, 9H), a 2.36 (s, 6H), 4,17 (kV, 1H,J=8.0 Hz), of 4.66 (s, 2H), was 7.08 (d, 2H,J=2.0 Hz), 7,28 (DD, 1H,J=4,0, 8.0 Hz), 7,73 (d, 1H,J=8.0 Hz), 7,89 (d, 1H,J=8.0 Hz), 8,08 (DD, 1H,J=4,0, 8.0 Hz), 8,58 (s, 1H); MS (ES) 358,0 (M+1).

CONNECTION 1-30 (Compound of formula III in which R2, R3and G1taken together, correspond to A*(see table 1), n2=1, Z=Ph, n3=0, n4=0): is Specified in the title compound was prepared as follows: a Solution of N-(tert-butoxycarbonyl)-L-Proline, 0°C, (1.65 g, 7,66 mmol) in DCM (25 ml) was uploaded by triethylamine (1.07 g, 7,66 mmol) and chloride diphenylphosphine (of 1.44 ml, 7,66 mmol) and left to warm to room temperature for 2 hours. The solvent was removed in vacuo, and the residue was distributed between ethyl ether and N2O. the Organic layer sequentially prom is Wali Na 2CO3(2×) and saturated brine (1×), dried over Na2SO4, filtered and concentrated in vacuum. The residue was dissolved in THF (25 ml) and cooled to -78°C. Separately, a suspension of 2-bromo-6-benzyloxyaniline (1.20 g, a 3.83 mmol) and Mg (0,140 g of 5.75 mmol) in THF (4.8 ml) was heated to 50°C for 30 minutes, was added CH3I (1 drop), was kept at 50°C for an additional 30 minutes, heated under reflux for 30 minutes, cooled to room temperature and was added dropwise to a cooled stirred solution of the anhydride, which is then left to warm to room temperature overnight with stirring. The solvent was removed in vacuo, and the residue was distributed between CH2Cl2and a mixture of 1:1 phosphate buffer:1 M citric acid. The organic layer was sequentially washed Na2CO3(2×) and saturated brine (1×), dried over Na2SO4, filtered and concentrated in vacuum. The residue was subjected to chromatography (gradient from 95% hexane:5% EtOAc-80% hexane:20% EtOAc)to obtain specified in the title compound as a white solid; melting point of 102-104°C.; MS (ES) 432,13 (M+1).

CONNECTION 1-31 (compound of formula III in which R2=CH2CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3n4= and Q 1=CO2CH3): The title compound was obtained by the above method And the total synthesis, which used the compound of formula IV, R2=CH2CH3, R3=H, and G1=N(CH3)2and the compound of formula V, A1=OH, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ of 0.89 (t, 3H, 7,4 Hz)to 1.38 (s, 6H), 1,78-to 1.79 (m, 1H), 1,92-to 1.98 (m, 1H), of 2.38 (s, 6H), 3,71 (s, 3H), 3,97-4,01 (m, 1H), 4,12 (s, 2H), 7,15 (d, 1H,J=2.3 Hz), 7,18 (DD, 1H,J=of 2.5 to 8.9 Hz), 7,76 (d, 1H,J=8.0 Hz), 7,86 (d, 1H,J=8.0 Hz), of 8.06 (DD, 1H,J=to 1.7, 8.6 Hz), charged 8.52 (s, 1H).

CONNECTION 1-32 (compound of formula III in which R2=CH3, R3=H, G1=N(CH3)iPr, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above method And the total synthesis, which used the compound of formula IV, R2=CH3, R3=H, and G1=N(CH3)iPr, and the compound of formula V, A1=OH, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et. MS (ES) 426,1 (M+1).

Following the above General methods, received the following intermediates of formula II, which are shown in table 2. In some intermediates "and" oboznachaet the SYN-amerosport, and "b" denotes anti-amerosport against G1.

1 1
Table 2
The list of intermediates of formula II
ConnectionR2R3G1n2Zn3R4bR5bn4Q1
2-1aCH3HN(CH3)20-1CH3CH31CO2CH3
2-1bCH3HN(CH3)20-1CH3CH3CO2CH3
2-2aCH3HN(CH3)214 Ph0--1CO2CH3
2-2bCH3HN(CH3)214 Ph0--1CO2CH3
2-3aCH3HN(CH3)213 Ph0--1CO2CH3
2-3bCH3HN(CH3)21 3 Ph0--1CO2CH3
2-4aCH3HN(CH3)214 Ph1HH1CO2CH3
2-4bCH3HN(CH3)214 Ph1HH1CO2CH3
2-5aCH3HN(CH3)20-1CH3CH31CH3
2-5bCH3/td> HN(CH3)20-1CH3CH31CH3
2-6aCH3HN(CH3)214 Ph0--1OtBu
2-6bCH3HN(CH3)214 Ph0--1OtBu
2-7aCH3HN(CH3)214 PhO1HH1 CO2CH3
2-7bCH3HN(CH3)214 PhO1HH1CO2CH3
2-8aCH3HN(CH3)20-2HH1OCH3
2-8bCH3HN(CH3)20-2HH1OCH3
2-9aCH3HN(CH3)214 Ph0 --1OCH3
2-9bCH3HN(CH3)214 Ph0--1OCH3
2-10aCH3HN(CH3)21TRANS
CH=CHPh
0--0-
2-10bCH3HN(CH3)21TRANS
CH=CHPh
0--0-
2-11aCH3HN(CH3)2 14 Ph0--1CN
2-11bCH3HN(CH3)214 Ph0--1CN
2-12aCH3HN(CH3)214 Ph0--1NO2
2-12bCH3HN(CH3)214 Ph0--1NO2
2-13aCH3 N(CH3)20-1EtEt1CO2Et
2-13bCH3HN(CH3)20-1EtEt1CO2Et
2-14aCH3HN(CH3)20-1CH2CH2ring1CO2Et
2-14bCH3HN(CH3)20-1CH2CH2ring1CO2 Et
2-15aCH3HN(CH3)20-1CH2CH2CH2ring1CO2Et
2-15bCH3HN(CH3)20-1CH2CH2CH2ring1CO2Et
2-16aCH3HN(CH3)20-1CH2CH2OCH2CH2ring1CO2CH3
2-16bCH3HN(CH3)20 -1CH2CH2OCH2CH2ring1CO2CH3
2-17aCH3HN(CH3)20-1CH2(CH2)3CH2ring1CO2Et
2-17bCH3HN(CH3)20-1CH2(CH2)3CH2ring1CO2Et
2-18aCH3HN(CH3)20-1CH2(CH2)2CH2ring1CO2 Et
2-18bCH3HN(CH3)20-1CH2(CH2)2CH2ring1CO2Et
2-19aCH3HN(CH3)21Ph0--0-
2-19bCH3HN(CH3)21Ph0--0-
2-20aCH3HN(CH2)2O(CH2)2ring0- CH3CH31CO2CH3
2-20bCH3HN(CH2)2O(CH2)2ring0-1CH3CH31CO2CH3
2-21aCH3HN(Et)20-1CH3CH31CO2CH3
2-21bCH3HN(Et)20-1CH3CH31CO2CH3
2-22a CH3HN(CH3)cyclo-hexyl0-1CH3CH31CO2CH3
2-22bCH3HN(CH3) cyclo-hexyl0-1CH3CH31CO2CH3
2-23aCH3HN(CH3)n-butyl0-1CH3CH31CO2CH3
2-23bCH3HN(CH3)n-butyl0-1 CH3CH31CO2CH3
2-24aCH3HN(CH3)iPr0-1CH3CH31CO2CH3
2-24bCH3HN(CH3)iPr0-1CH3CH31CO2CH3
2-25aCH3HN(CH3)Ph0-1CH3CH31CO2CH3
2-26aCH3 HN(CH2)4ring0-1CH3CH31CO2CH3
2-26bCH3HN(CH2)4ring0-1CH3CH31CO2CH3
2-27CH3CH3N(CH3)20-1CH3CH31CO2CH3
2-28aCH3HN(CH3)Et0-1CH3 CH31CO2CH3
2-28bCH3HN(CH3)Et0-1CH3CH31CO2CH3
2-29aCH3HN(CH3)20-0--1CO2tBu
2-29bCH3HN(CH3)20-0--1CO2tBu
2-30HHN(CH3)2 0-1CH3CH31CO2CH3
2-31aA2*1Ph0--0-
2-31bA2*1Ph0--0-
2-32aEtHN(CH3)20-1CH3CH31CO2CH3
2-32bEtHN(CH3)20-CH3CH31CO2CH3
2-33aCH3HN(CH3)iPr0-1CH2(CH2)2CH2ring1CO2Et
2-33bCH3HN(CH3)iPr0-1CH2(CH2)2CH2ring1CO2Et

in which A2*=R2R3G, together with the carbon to which they attach, form

in which • denotes the carbon to which they attach.

Way With the General synthesis for the preparation of compounds of formula IIa/b: a Solution of the compounds of formula III (1 EQ.) in CH3OH (0.3 M) was cooled to 0°C. sodium Borohydride (1 EQ.) added by portions at 0°C and the reaction to the offer was left to warm to room temperature and was stirred for 1.5 hours. The reaction mixture was concentrated in vacuum, distributed between NaHCO3and CH2Cl2and the aqueous layer was extracted with 5× CH2Cl2. Obyedinennye organic layers were dried over Na2SO4, filtered and concentrated in vacuum. The crude product was purified by the method of column chromatography on silica gel (gradient of CH2Cl2up to 5% CH3OH:CH2Cl2with 1% Et3N)to obtain the required SYN - and anti-isomers, a and b respectively, the compounds of formula II.

The COMPOUND 2-1A (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) d to 0.72 (d, 3H,J=6,6 Hz)of 1.36 (s, 6H), was 2.34 (s, 6H), 2,63 of 2.68 (m, 1H), 3,71 (s, 3H), 4,08 (s, 2H), 4,32 (d, 1H,J=9.8 Hz), 7,11-7,14 (m, 2H), 7,26 (s, 1H), 7,66-7,74 (m, 3H); MS (ES 360,0 (M+1).

CONNECTION 2-1b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained according to the description of nomu above method C total synthesis where used, the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ of 0.85 (d, 3H,J=6,6 Hz)of 1.36 (s, 6H), was 2.34 (s, 6H), 2,63 of 2.68 (m, 1H), 3,71 (s, 3H), 4,08 (s, 2H), 5,13 (d, 1H,J=3.6 Hz), 7,11-7,14 (m, 2H), 7,26 (s, 1H), 7,66-7,74 (m, 3H); MS (ES 360,0 (M+1).

CONNECTION 2-2A (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ to 0.73 (d, 3H,J=6,8 Hz), of 2.33 (s, 6H), 2,61 of 2.68 (m, 1H), 3,93 (s, 3H), 4,33 (d, 1H,J=9.6 Hz), of 5.24 (s, 2H), 7,16-7,24 (m, 2H), 7,37 (DD, 1H,J=8,4 Hz, 1.2 Hz), 7,56 (d, 2H,J=4.0 Hz), 7,66-to 7.77 (m, 3H), 8,06-8,08 (m, 2H); MS (ES) 393,9 (M+1).

CONNECTION 2-2b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=CO2CH3. 1H NMR (CDCl3, 200 MHz) δ of 0.83 (d, 3H,J=6,8 Hz), 2,39 (s, 6H), 2,61 of 2.68 (m, 1H), 3,93 (s, 3H), 5,10 (d, 1H,J=3.2 Hz), of 5.24 (s, 2H), 7,17-7,24 (m, 2H), 7,47 (DD, 1H,J=2,0, 8,8 Hz), 7,56 (d, 2H,J=8.0 Hz), 7,66-to 7.77 (m, 3H), 8,06-8,08 (m, 2H); MS (ES) 393,9 (M+1).

CONNECTION 2-3a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=3-phenyl, n3=0, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula II, R2=CH3, R3=H, and G1=N(CH3)2, n2=1, Z=3-phenyl, n3=0, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ to 0.73 (d, 3H,J=6,6 Hz), was 2.34 (s, 6H), 2.63 in-a 2.71 (m, 1H), 3,93 (s, 3H), 4,33 (d, 1H,J=9.4 Hz), to 5.21 (s, 2H), 7,20 (s, 1H), 7,24 (s, 1H), 7,35-7,52 (m, 2H), 7,66-7,73 (m, 3H), to 7.77 (s, 1H), 8,00-of 8.04 (m, 1H), 8,17 (s, 1H); MS (ES) 394,0 (M+1).

CONNECTION 2-3b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=3-phenyl, n3=0, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=1, Z=3-phenyl, n3=0, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ of 0.89 (d, 3H,J=6,6 Hz), a 2.45 (s, 6H), 2,94-to 3.02 (m, 1H), 3,93 (s, 3H), 4,33 (d, 1H,J=9.4 Hz), to 5.21 (s, 2H), 7,20 (s, 1H), 7,24 (s, 1H), 7,35-7,52 (m, 2H), 7,66-7,73 (m, 3H), to 7.77 (s, 1H),8,00-of 8.04 (m, 1H), 8,17 (s, 1H); MS (ES) 394,0 (M+1).

CONNECTION 2-4a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=1, R4aand R4b=H, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2n2=1, Z=4-phenyl, n3=1, R4aand R4b=H, n4=1 and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ to 0.73 (d, 3H,J=and 6.6 Hz), was 2.34 (s, 6H), 2,58 is 2.75 (m, 1H), the 3.65 (s, 2H), 3,70 (s, 3H), 4,35 (d, 1H,J=10,0 Hz), 5,16 (s, 2H), 7.18 in-7,34 (m, 4H), 7,38-to 7.50 (m, 3H), to 7.67-7,76 (m, 3H).

CONNECTION 2-4b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=1, R4band R5b=H, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2n2=1, Z=4-phenyl, n3=1, R4band R5b=H, n4=1 and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ of 0.65 (d, 3H,J=and 6.6 Hz), 2,39 (s, 6H), 2,58 is 2.75 (m, 1H), the 3.65 (s, 2H), 3,70 (s, 3H), 4,35 (d, 1H,J=10,0 Hz), 5,16 (s, 2H), 7.18 in-7,34 (m, 4H), 7,38-to 7.50 (m, 3H), to 7.67-7,76 (m, 3H); MS (ES) 408,0 (M+1).

CONNECTION 2-5a (compound of formula II in which R2=CH3 , R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2n2=0, n3=1, R4band R5b=CH3n4=1 and Q1=CH3.1H NMR (CDCl3, 200 MHz) δ to 0.73 (d, 3H,J=3.6 Hz), a 1.08 (s, 9H), was 2.34 (s, 6H), 2,66-2,69 (m, 1H), 3,71 (s, 1H), 4,32 (d, 1H,J=10,0 Hz), 5,12 (s, 2H), 7,11 (s, 1H), 7,16 (d, 1H,J=8,8 Hz), 7,35 (d, 1H,J=the 7.4 Hz), was 7.45 (d, 1H,J=and 8.4 Hz), to 7.67 to 7.75 (m, 2H); MS (ES) was 316.0 (M+1).

CONNECTION 2-5b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CH3.1H NMR (CDCl3, 200 MHz) δ of 0.85 (d, 3H,J=3.6 Hz), a 1.08 (s, 9H), is 2.41 (s, 6H), 2,66-2,69 (m, 1H), 3,71 (s, 1H), 4,32 (d, 1H,J=10,0 Hz), 5,12 (s, 2H), 7,11 (s, 1H), 7,16 (d, 1H,J=8,8 Hz), 7,35 (d, 1H,J=the 7.4 Hz), was 7.45 (d, 1H,J=and 8.4 Hz), to 7.67 to 7.75 (m, 2H); MS (ES) was 316.0 (M+1).

CONNECTION 2-6a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-f the Nile, n3=0, n4=1, and Q1=OtBu): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n=1 and Q1=OtBu.1H NMR (CDCl3, 200 MHz) δ to 0.73 (d, 3H,J=6,0 Hz)of 1.36 (s, 9H), was 2.34 (s, 6H), 2,63-of 2.72 (m, 1H), 4,33 (d, 1H,J=8.0 Hz), 5,11 (s, 2H), 7,00? 7.04 baby mortality (m, 2H), 7,20-of 7.23 (m, 2H), was 7.36-7,49 (m, 3H), 7,69 to 7.75 (m, 3H); MS (ES) 408,0 (M+1).

CONNECTION 2-6b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=OtBu): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=OtBu.1H NMR (CDCl3, 200 MHz) δ of 0.87 (d, 3H,J=6,0 Hz)of 1.36 (s, 9H), 2,43 (s, 6H), 2,63-of 2.72 (m, 1H), 5,11 (s, 2H), 5,16 (d, 1H,J=4.0 Hz), 7,00? 7.04 baby mortality (m, 2H), 7,20-of 7.23 (m, 2H), was 7.36-7,49 (m, 3H), 7,69 to 7.75 (m, 3H); MS (ES) 408,0 (M+1).

CONNECTION 2-7a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-PhO, n3=1, R4band R5b=H, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=1, Z=4-PhO, n3=1, R4b and R5b=H, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ to 0.73 (d, 3H,J=6,0 Hz), was 2.34 (s, 6H), 2,64-of 2.72 (m, 1H), 3,81 (s, 3H), 4,34 (d, 1H,J=8,0 Hz)and 4.65 (s, 2H), 5,10 (s, 2H) 6,92-of 6.96 (m, 2H), 7,17-7,21 (m, 2H), 7,39-7,46 (m, 3H), 7.68 per to 7.75 (m, 3H); MS (ES) 424,0 (M+1).

CONNECTION 2-7b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-PhO, n3=1, R4band R5b=H, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=1, Z=4-PhO, n3=1, R4band R5b=H, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ of 0.90 (d, 3H,J=6,0 Hz), 2,46 (s, 6H), 2,64-of 2.72 (m, 1H), 3,81 (s, 3H)and 4.65 (s, 2H), 5,10 (s, 2H), 5,22 (d, 1H,J=4.0 Hz), 6,92-of 6.96 (m, 2H), 7,17-7,21 (m, 2H), 7,39-7,46 (m, 3H), 7.68 per to 7.75 (m, 3H); MS (ES) 424,0 (M+1).

CONNECTION 2-8a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=2, R4band R5b=H, n4=1, and Q1=OCH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=2, R4band R5b=H, n4=1, and Q1=OCH3. MS (ES) 304,3 (M+1).

CONNECTION 2-8b (compound of formula II in which R2=CH3, R3=H, G 1=N(CH3)2, n2=0, n3=2, R4band R5b=H, n4=1, and Q1=OCH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=2, R4band R5b=H, n4=1, and Q1=OCH3. MS (ES) 304,3 (M+1).

CONNECTION 2-9a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=OCH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=OCH3. MS (ES) 366,4 (M+1).

CONNECTION 2-9b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=OCH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=OCH3. MS (ES) 366,4 (M+1).

CONNECTION 2-10a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z corresponds to TRANS-CH=CHPh, n3 and n4=0): is Specified in the title compound was obtained as described is use method C total synthesis where used, the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=1 Z=corresponds to TRANS-CH=CHPh, n3 and n4=0. MS (ES) 362,3 (M+1).

CONNECTION 2-10b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z corresponds to TRANS-CH=CHPh, n3 and n4=0): is Specified in the title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=1 Z=corresponds to TRANS-CH=CHPh, n3 and n4=0. MS (ES) 362,3 (M+1).

CONNECTION 2-11a/b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=CN): The title compound was obtained as a mixture of SYN - and anti-isomers of the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=CN. MS (ES) 361,2 (M+1).

CONNECTION 2-12a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=NO2): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=NO .1H NMR (CDCl3, 400 MHz) δ to 0.73 (d, 3H,J=6,4 Hz), of 2.33 (s, 6H), 2,63-2,70 (m, 1H), 4,33 (d, 1H,J=12.0 Hz), 5,28 (s, 2H), 7,15 (d, 1H,J=2.0 Hz), 7,21 (DD, 1H,J=2,8, 8,8 Hz), 7,38-7,52 (m, 2H), 7,60 (d, 2H,J=8,4 Hz), to 7.67-of 7.70 (m, 2H), 7,74 (s, 1H), 7,75 for 7.78 (m, 1H).

CONNECTION 2-12b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=NO2): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=NO2.1H NMR (CDCl3, 400 MHz) δ to 0.73 (d, 3H,J=6,4 Hz), of 2.33 (s, 6H), 2,63-2,70 (m, 1H), 4,33 (d, 1H,J=12.0 Hz), 5,28 (s, 2H), 7,15 (d, 1H,J=2.0 Hz), 7,21 (DD, 1H,J=2,8, 8,8 Hz), 7,38-7,52 (m, 2H), 7,60 (d, 2H,J=8,4 Hz), to 7.67-of 7.70 (m, 2H), 7,74 (s, 1H), 7,75 for 7.78 (m, 1H).

CONNECTION 2-13a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH2CH3, n4=1, and Q1=CO2Et): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH2CH3, n4=1, and Q1=CO2Et.1H NMR (CDCl3, 400 MHz) δ to 0.72 (d, 3H,J=6,8 Hz)to 0.85 (t, 6H,J=a 7.6 Hz), 1.26 in (t, 3H,J=7,2 Hz), 1,78-1,83 (who, 4H), of 2.33 (s, 6H), 2.63 in-a 2.71 (m, 1H), 4,15 (s, 2H), 4,20 (q, 2H,J=6,4 Hz, 14,0 Hz)to 4.33 (d, 1H,J=9.6 Hz), 7,12 (DD, 1H,J=2,8 Hz and 8.8 Hz), 7,19 (d, 1H,J=the 2.4 Hz), 7,46 (d, 1H,J=8,8 Hz), 7,69-7,73 (m, 3H); MS (ES) 402,3 (M+1).

CONNECTION 2-13b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH2CH3, n4=1, and Q1=CO2Et): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH2CH3, n4=1, and Q1=CO2Et. MS (ES) 402,3 (M+1).

CONNECTION 2-14a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopropyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopropyl, n4=1, and Q1=CO2Et.1H NMR (CDCl3, 400 MHz) δ to 0.73 (d, 3H,J=6,4 Hz), 1,09 (q, 2H,J=the 3.2 Hz), 1,22 (t, 3H,J=a 7.6 Hz), 1.39 in (q, 2H,J=2,8 Hz), was 2.34 (s, 6H), 2,3-2,71 (m, 1H), 4,17 (q, 2H,J=7,2 Hz), 4,25 (s, 2H), 4,33 (d, 1H,J=8.0 Hz), 7,13 (s, 1H), 7,15 (d, 1H), 7,45 (d, 1H,J=and 8.4 Hz), 7,69-7,72 (m, 3H).

CONNECTION 2-14b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopropyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopropyl, n4=1, and Q1=CO2Et. MS (ES) 372,0 (M+1).

CONNECTION 2-15a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclobutyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclobutyl, n4=1, and Q1=CO2Et.1H NMR (CDCl3, 400 MHz) δ of 0.74 (d, 3H,J=6,6 Hz) 1,23-of 1.30 (m, 3H), 2,03-2,07 (m, 2H), 2,19-of 2.21 (m, 2H), 2,35 (s, 6H), 2,55-of 2.58 (m, 2H), 2,60-of 2.75 (m, 1H), 4,17-4,24 (m, 2H), or 4.31-to 4.38 (m, 3H), 7,15 (DD, 1H,J=of 2.5 Hz and 8.8 Hz), 7,18 (d, 1H,J=the 2.4 Hz), of 7.48 (DD, 1H,J=1,6 Hz, 8.6 Hz), 7,71-7,74 (m, 3H).

CONNECTION 2-15b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclobutyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclobutyl, n4=1, and Q1=CO2Et. MS (ES) 386,3 (M+1).

CONNECTION 2-16a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring of 4-pyranyl, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring of 4-pyranyl, n4=1, and Q1=CO 2CH3.1H NMR (CDCl3, 400 MHz) δ to 0.73 (d, 3H), 1,75-to 1.82 (m, 2H), 2,23-to 2.29 (m, 2H), 2,34 (s, 6H), to 2.66 (m, 1H), 3,57-to 3.64 (m, 2H, in), 3.75 (s, 3H), 3,86-3,93 (m, 2H), 4,12 (s, 2H), 4,34 (d, 1H,J=9.8 Hz), 7,10 (s, 1H), 7,13 (d, 1H,J=the 2.6 Hz), of 7.48 (DD, 1H,J=1,4 Hz, 8.5 Hz), 7.68 per-7,76 (m, 3H).

CONNECTION 2-16b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring of 4-pyranyl, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring of 4-pyranyl, n4=1, and Q1=CO2CH3. MS (ES) 402,2 (M+1).

CONNECTION 2-17a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a cyclohexyl ring, n4=1, and Q1=CO2Et): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which the WMD they were annexed, form a cyclohexyl ring, n4=1, and Q1=CO2Et.1H NMR (CDCl3, 400 MHz) δ of 0.71 (d, 3H, 9.9 Hz), of 1.23 (t, 3H,J=2,10), 1,30-of 1.36 (m, 2H), 1,47-is 1.51 (m, 3H), 1,52-of 1.64 (m, 3H), 2,20-of 2.23 (m, 2H), 2,35 (s, 6H), 2,67-a 2.71 (m, 1H), 4.09 to (s, 2H), 4,20 (q, 2H,J=7,1 Hz, 7,10), 4,34 (d, 1H, 9.7 Hz), 7,11 (s, 1H), 7,13 (d, 1H,J=the 2.5 Hz), 7,47 (DD, 1H,J=1,6 Hz, 8.5 Hz), 7,69-7,72 (m, 3H).

CONNECTION 2-17b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a cyclohexyl ring, n4=1, and Q1=CO2Et): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a cyclohexyl ring, n4=1, and Q1=CO2Et. MS (ES) 414,3 (M+1).

CONNECTION 2-18a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3) 2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et.1H NMR (CDCl3, 400 MHz) δ to 0.72 (d, 3H,J=6,6 Hz)to 1.21 (t, 3H,J=7,1 Hz), 1,63-to 1.82 (m, 6H), 2,16-of 2.21 (m, 2H), 2,34 (s, 6H), 2,65-2,69 (m, 1H), 4.09 to is 4.21 (m, 4H), to 4.33 (d, 1H,J=the 9.7 Hz), 7,10 (d, 1H,J=the 2.5 Hz), 7,13 (s, 1H), 7,46 (DD, 1H,J=of 1.6 Hz and 8.4 Hz), of 7.64-7,71 (m, 3H).

CONNECTION 2-18b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et. MS (ES) 400,3 (M+1).

CONNECTION 2-19a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=Ph, n3 and n4=0): is Specified in the title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=1, Z=Ph, n3 and n4=0.1H NMR (CDCl3, 200 MHz) δ of 0.74 (d, 3H,J=6 Hz), of 2.35 (s, 6H), 2,68 was 2.76 (m, 1H), 4,35 (d, 1H,J=10.0 Hz), 5,16 (s, 2H), 7.18 in for 7.78 (m, 11H); MS (ES) 336,1 (M+1).

CONNECTION 2-19b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=Ph, n3 and n4=0): is Specified in the title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=1, Z=Ph, n3 and n4=0.1H NMR (CDCl3, 200 MHz) δ and 0.98 (d, 3H,J=8.0 Hz), 2,62 (s, 6H), 2,68 was 2.76 (m, 1H), 5,16 (s, 2H), 5,45 (shirt, 1H), 7.18 in for 7.78 (m, 11H); MS (ES) 336,1 (M+1).

CONNECTION 2-20a (compound of formula II in which R2=CH3, R3=H, G1=N(CH2)2O(CH2)2-ring, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH2)2O(CH2)2-ring, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ of 0.79 (d, 3H,J=6,8 Hz)of 1.36 (s, 3H), 2,49-of 2.54 (m, 2H), 2,64-2,70 (m, 1H), 2,74-and 2.79 (m, 2H, in), 3.75 (s, 3H), 3,76-of 3.85 (m, 4H), 4,08 (s, 2H), 4,39 (d, 1H,J=10.0 Hz), 7,11-7,14 (m, 2H), 7,44 (DD, 1H,J=8,8 Hz, 1.6 Hz), 7,70-7,72 (m, 3H).

CONNECTION 2-20b (compound of formula II in which R2=CH3, R3=H, G1=N(CH2)2O(CH2)2-also, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH2)2O(CH2)2-ring, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ of 0.83 (d, 3H,J=6,8 Hz)of 1.36 (s, 3H), 2,49-of 2.54 (m, 2H), 2,64-2,70 (m, 1H), 2,74-and 2.79 (m, 2H, in), 3.75 (s, 3H), 3,76-of 3.85 (m, 4H), 4,08 (s, 2H), is 4.93 (d, 1H,J=4.0 Hz), 7,11-7,14 (m, 2H), 7,44 (DD, 1H,J=8,8 Hz, 1.6 Hz), 7,70-7,72 (m, 3H).

CONNECTION 2-21a (a compound of the formula II in which R2=CH3, R3=H, G1=N(Et)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(Et)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ of 0.77 (d, 3H,J=6,8 Hz)of 1.16 (t, 6H,J=7,2 Hz), of 1.37 (s, 6H), 2,38 is 2.46 (m, 2H), 2,69-2,78 (m, 2H), 2,79-of 2.86 (m, 1H), 3,71 (s, 3H), 4,08 (s, 2H), 4,32 (d, 1H,J=10.0 Hz), 7,12-to 7.15 (m, 2H), 7,47 (DD, 1H,J=8,4 Hz, 1.6 Hz), 7,70-7,72 (m, 3H).

CONNECTION 2-21b (compound of formula II in which R2=CH3, R3=H, G1=N(Et)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2 CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(Et)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ to 0.92 (d, 3H,J=6,8 Hz)of 1.05 (t, 6H,J=7,2 Hz), of 1.36 (s, 6H), 2,53-of 2.54 (m, 4H), 3,09-3,17 (m, 1H), of 3.07 (s, 3H), 4,08 (s, 2H), 4,89 (s, 1H), 7,11-7,14 (m, 2H), 7,38 (DD, 1H,J=8,8 Hz, 1.2 Hz), to 7.67-7,72 (m, 3H).

CONNECTION 2-22a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)-cyclohexyl, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)-cyclohexyl, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ 0,76 (d, 3H,J=6,8 Hz), 1,13-of 1.16 (m, 1H), 1,24 to 1.31 (m, 3H), of 1.39 (s, 6H), 1,45-1,49 (m, 1H), 1,64 was 1.69 (m, 1H), 1,82-of 1.85 (m, 3H), 1,96-to 1.98 (m, 1H), 2,32 (s, 3H), of 2.51-2.57 m (m, 1H), 2,86-to 2.94 (m, 1H), and 3.72 (s, 3H), 4,10 (s, 2H), 4,27 (d, 1H,J=9,2 Hz), 7,13-7,16 (m, 2H), of 7.48 (DD, 1H,J=8,4 Hz, 2.0 Hz), 7,71-7,74 (m, 3H).

CONNECTION 2-22b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)-cyclohexyl, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): Specified the title compound was obtained by the above described method C total synthesis where used, the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)-cyclohexyl, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ of 0.89 (d, 3H,J=6,8 Hz), 1,08-1,15 (m, 1H), 1,22-of 1.33 (m, 3H), of 1.39 (s, 6H), 1,44-1,49 (m, 1H), 1,64-to 1.67 (m, 1H), 1,75-to 1.87 (m, 4H), of 2.23 (s, 3H), 2,59-to 2.65 (m, 1H), 3,09-3,13 (m, 1H), and 3.72 (s, 3H), 4,10 (s, 2H), 4.92 in (C, 1H), 7,13-7,16 (m, 2H), 7,39 (DD, 1H,J=8,4 Hz, 1.6 Hz), 7.68 per to 7.75 (m, 3H).

CONNECTION 2-23a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)-n-butyl, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)-n-butyl, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ 0,76 (d, 3H,J=6,8 Hz), 0,99 (t, 3H,J=6,8 Hz)of 1.39 (s, 6H), 1,40-1,45 (m, 1H), 1,52-to 1.61 (m, 3H), 2,31 (s, 3H), 2,38 is 2.43 (m, 1H), 2,56-2,63 (m, 1H), 2,70 was 2.76 (m, 1H), of 3.73 (s, 3H), 4,10 (s, 2H), 4,37 (d, 1H,J=9.6 Hz), 7,13-7,16 (m, 2H), of 7.48 (DD, 1H,J=2,0, 8,8 Hz), 7,71-7,74 (m, 3H).

CONNECTION 2-23b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)-n-butyl, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total Sint is for, where used, the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)-n-butyl, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ of 0.89 (d, 3H,J=7,2 Hz), of 0.93 (t, 3H,J=7,2 Hz), of 1.27 to 1.34 (m, 2H), 1.39 in (s, 6H), 1,47-of 1.55 (m, 2H), 2,30 (s, 3H), 2,47-of 2.58 (m, 2H), 2,90-to 2.94 (m, 1H), of 3.73 (s, 3H), 4,10 (s, 2H), 4,99 (d, 1H,J=3.6 Hz), 7,13-7,16 (m, 2H), 7,39 (DD, 1H,J=1,6, and 8.4 Hz), 7,69-7,76 (m, 3H).

CONNECTION 2-24a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)iPr, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)iPr, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ of 0.82 (d, 3H,J=6,8 Hz)of 1.11 (d, 3H,J=7,6 Hz), 1.14 in (d, 3H,J=8,4 Hz)of 1.36 (s, 6H), and 2.26 (s, 3H), 2,84-is 2.88 (m, 1H), 2,96-to 3.02 (m, 1H), 3,71 (s, 3H), 4,08 (s, 2H), 4.25 in (d, 1H,J=9,2 Hz), 7,13-7,16 (m, 2H), 7,46 (DD, 1H,J=8,4 Hz, 1.6 Hz), 7,69 to 7.75 (m, 3H).

CONNECTION 2-24b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)iPr, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound is of ormolu III, R2=CH3, R3=H, and G1=N(CH3)iPr, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ 0,86 (d, 3H,J=6,8 Hz)of 1.07 (d, 3H,J=6,4 Hz)of 1.12 (d, 3H,J=6,4 Hz)of 1.39 (s, 6H), of 2.21 (s, 3H), 2,99-to 3.02 (m, 1H), 3,15-3,18 (m, 1H), 3,70 (s, 3H), 4,10 (s, 2H), 4.95 points (d, 1H,J=4.0 Hz), 7,13-7,16 (m, 2H), 7,39 (DD, 1H,J=8,4 Hz, 1.6 Hz), 7,69 to 7.75 (m, 3H).

CONNECTION 2-25a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)Ph, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)Ph, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ 0,86 (d, 3H,J=6,8 Hz)of 1.36 (s, 6H), 2,84 (s, 3H), 3,70 (s, 3H), 3,88-to 3.92 (m, 1H), and 4.68 (d, 1H,J=9.6 Hz), 6,86-of 6.90 (m, 1H), 7,05-was 7.08 (m, 2H), 7,13-7,16 (m, 2H), 7,28-7,33 (m, 2H), 7,56 (DD, 1H,J=8,4 Hz, 1.6 Hz), 7,72-7,76 (m, 2H), 7,80 (s, 1H).

CONNECTION 2-26a (compound of formula II in which R2=CH3, R3=H, G1=N(CH2)4-ring, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH2 )4-ring, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ 0,78 (d, 3H,J=6,4 Hz)of 1.36 (s, 6H), 1,78-to 1.87 (m, 4H), 2,67-2,78 (m, 4H), 2,97 was 3.05 (m, 1H), 3,70 (s, 3H), 4,08 (s, 2H), 4,36 (d, 1H,J=10.0 Hz), 7,11-7,14 (m, 2H), 7,47 (DD, 1H,J=8,4 Hz, 1.6 Hz), 7,69-7,73 (m, 3H).

CONNECTION 2-26b (compound of formula II in which R2=CH3, R3=H, G1=N(CH2)4-ring, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH2)4-ring, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ 0,81 (d, 3H,J=6,4 Hz)of 1.36 (s, 6H), 1,82-1,89 (m, 4H), 2,58-2,61 (m, 1H), 2,66-and 3.72 (m, 2H), 2,80-is 2.88 (m, 2H), 3,71 (s, 3H), 4,08 (s, 2H), 5,15 (d, 1H,J=2,4 Hz), 7,12-7,14 (m, 2H), was 7.36 (DD, 1H,J=8,4 Hz, 1.6 Hz), to 7.67-7,74 (m, 2H), to 7.77 (s, 1H).

CONNECTION 2-27 (compound of formula II in which R2=CH3, R3=CH3, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=CH3and G1=N(CH3)2, n2=0, n3=1, R4band R5b/sup> =CH3, n4=1, and Q1=CO2CH3. MS (ES) 374,3 (M+1).

CONNECTION 2-28a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)Et, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)Et, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ of 0.74 (d, 3H,J=6,8 Hz)of 1.16 (t, 3H,J=6,8 Hz)of 1.36 (s, 6H), to 2.29 (s, 3H), 2,41-2,49 (m, 1H), 2,61-2,69 (m, 1H), 2.71 to 2,78 (m, 1H), 3,71 (s, 3H), 4,08 (s, 2H), 4,34 (d, 1H,J=9.6 Hz), 7,11-7,14 (m, 2H), 7,46 (DD, 1H,J=8.0 Hz, 1.6 Hz), 7,69-7,71 (m, 3H).

CONNECTION 2-28b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)Et, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)Et, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ was 1.04 (d, 3H,J=7,2 Hz), of 1.30 (t, 3H,J=7,2 Hz), of 1.36 (s, 6H), to 2.65 (s, 3H), 2,88-of 2.93 (m, 1H), 3.04 from-of 3.07 (m, 1H), 3,23-of 3.27 (m, 1H), 3,70 (s, 3H), 4,07 (s, 2H), to 5.58 (s, 1H), 7,09-7,13 (m, 2H), 7,44 (DD, 1H,J=8,4 Hz, 1.6 Hz), 7,63-of 7.70 (m, 2H), 7,79 (s, 1H).

SOY IS INANIA 2-29a (compound of formula II, in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=0, n4=1, and Q1=CO2tBu): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=0, n4=1, and Q1=CO2tBu.1H NMR (CDCl3, 200 MHz) δ of 0.71 (d, 3H,J=6,6 Hz), for 1.49 (s, 9H), of 2.33 (s, 6H), 4,32 (d, 1H,J=9.4 Hz), to 4.62 (s, 2H),? 7.04 baby mortality-7,06 (m, 1H), 7.18 in-7,24 (m, 1H), 7,34-7,49 (m, 1H), of 7.64-to 7.77 (m, 3H); MS (ES) 360,0 (M+1).

CONNECTION 2-29b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=0, n4=1, and Q1=CO2tBu): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)2, n2=0, n3=0, n4=1, and Q1=CO2tBu.1H NMR (CDCl3, 200 MHz) δ of 0.82 (d, 3H,J=6,6 Hz), for 1.49 (s, 9H), of 2.38 (s, 6H), and 4.75 (s, 2H), 5,07 (d, 1H, J=3.6 Hz),? 7.04 baby mortality-7,06 (m, 1H), 7.18 in-7,24 (m, 1H), 7,34-7,49 (m, 1H), of 7.64-to 7.77 (m, 3H); MS (ES) 360,0 (M+1).

CONNECTION 2-30 (compound of formula II in which R2=H, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was prepared as follows: Intermediate a-8 (200 mg, of 0.53 mmol) was dissolved in a mixture of 1:1 CH2Cl2:CH3OH (2 ml) and cooled to 0 is C. The solution was loaded NaBH4(30 mg, 0.79, which mmol) and left to warm to room temperature. After 4 hours the reaction mixture was loaded 2 M HN(CH3)2in CH3OH (10 EQ., 5.3 mmol) at room temperature. After 24 hours the reaction mixture was concentrated in vacuum, distributed between CH2Cl2and saturated aqueous NaHCO3and the aqueous layer was extracted with CH2Cl2(2×). The organic layers were dried over Na2SO4and concentrated in vacuum. The crude product was purified by chromatography on silica gel (2% CH3OH: CH2Cl2to obtain the desired product as a yellow resin. MS (ES) 346,0 (M+1).

CONNECTION 2-31a and 2-31b (compound of formula II in which R2, R3, G1taken together, correspond A2*(see table 2), n2=1, Z=Ph, and n3 and n4=0): is Specified in the title compound was prepared as follows: Into a solution of compound 1-30, 0°C, (of 0.43 g, 1.0 mmol) in THF (6 ml) was added LiAlH4(0.11 g, 3.0 mmol), the mixture was heated to 50°C for 3 hours, cooled to room temperature, poured on ice and was extracted with EtOAc (3×). The organic layer was subsequently dried over Na2SO4, filtered and concentrated in vacuum. The residue was purified by the method of column chromatography on silica gel (gradient from 100% CHCl3up to 99% CHCl3:1% CH3OH (NH3the feast upon.), to receive shall be specified in the title compound 2-31a and 2-31b. Connection 2-31a: white solid, melting point 108-110°C;1H NMR (CDCl3, 400 MHz) δ 1.25 and 1.32 to (m, 1H), 1,61-to 1.77 (m, 3H), 2,34-to 2.40 (m, 1H), of 2.51 (s, 3H), 2,60-of 2.64 (m, 1H), 3,15-3,19 (m, 1H), 5,00 (d, 1H,J=2,8 Hz), is 5.18 (s, 2H), 7,22-7,26 (m, 2H), 7,34-the 7.43 (m, 3H), 7,49 (d, 2H,J=7,6 Hz), 7,69 (d, 1H,J=8,4 Hz), 7,76 (d, 1H,J=8,8 Hz), 7,82 (s, 1H); MS (ES) 348,31 (M+1), 330,28 (M-18, no-HE). Connection 2-31b: white solid, melting point 84-87°C;1H NMR (CDCl3, 400 MHz) δ 1,76-of 1.81 (m, 3H), 1,82-of 1.94 (m, 1H, in), 2.25 (s, 3H), 2,41 is 2.51 (m, 1H), 2,84-87 (m, 1H), 3,14-3,17 (m, 1H), 4,49 (d, 1H,J=5,2 Hz), is 5.18 (s, 2H), 7,21-7,24 (m, 2H), 7,34 (d, 1H,J=7,6 Hz), 7,40-to 7.50 (m, 5H), of 7.70 (d, 1H,J=8,8 Hz), of 7.75 (d, 1H,J=10.0 Hz), 7,78 (s, 1H); MS (ES) 348,31 (M+1), 330,26. (M-18, no-HE).

CONNECTION 2-32a (compound of formula II in which R2=CH2CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH2CH3, R3=H, and G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ 0,58 (t, 3H, 7,6 Hz), 1,13-1,24 (m, 1H), 1,36 (s, 6H), 1,50-to 1.61 (m, 1H), 2,47 (s, 6H), 2,47 of $ 2.53 (m, 1H), 3,71 (s, 3H), 4,08 (s, 2H), 4,27 (d, 1H,J=9.6 Hz), 7,11-7,14 (m, 2H), of 7.48 (DD, 1H,J=of 1.5 and 8.4 Hz), 7,69-7,72 (m, 3H).

CONNECTION 2-32b (compound of formula II in which R2=CH2CH3,R 3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH2CH3, R3=H, and G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ 0,81 (t, 3H, 7.5 Hz), of 1.36 (s, 6H), 1,49-to 1.67 (m, 1H), 2,59 (s, 6H), 2,84-2,89 (m, 1H), 3,71 (s, 3H), 4,08 (s, 2H), 5,33 (d, 1H,J=3.1 Hz), 7,13 (s, 1H), 7,15 (d, 1H,J=the 2.4 Hz), 7,39 (DD, 1H,J=of 1.6, 8.5 Hz), of 7.70 (q, 2H,J=8.6 Hz), and 7.8 (s, 1H).

CONNECTION 2-33a (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)iPr, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)iPr, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et.1H NMR (CDCl3, 400 MHz) δ is 0.84 (d, 3H,J=6,6 Hz)of 1.12 (d, 3H,J=a 6.5 Hz), of 1.16 (d, 3H,J=a 6.5 Hz), to 1.21 (t, 3H,J=7,1 Hz), 1,67-of 1.84 (m, 6H), 2,16-of 2.21 (m, 2H), 2,28 (s, 3H), 2,83-2,90 (m, 1H), 2,94 totaling 3.04 (m, 1H), 4,14-4,19 (m, 4H), 4,24 (d, 1, J=9.4 Hz), 7,10-7,13 (m, 2H), 7,46 (DD, 1H,J=1.5 Hz, 8.6 Hz), 7,69 (s, 1H), 7,71 (s, 1H).

CONNECTION 2-33b (compound of formula II in which R2=CH3, R3=H, G1=N(CH3)iPr, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above described method C total synthesis, which used the compound of formula III, R2=CH3, R3=H, and G1=N(CH3)iPr, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et. MS (ES) 428,0 (M+1).

Following the General methods described above, were obtained the following compounds of formula I (in which R1=H, n1=1, R6a=H, R6b=H, Y=O, R4a=H, R5a=H), which are shown in table 3. In the rooms of the examples of "a" indicates SYN-isomer, and "b" denotes the anti-isomer relative to X and G1. X1=imidazol-1-yl, X2=triazole and X3=triazole-3-yl.

td align="center"> 0 -
Table 3
The list of compounds of formula I
ExampleR2R3 G1n2Zn3R4bR5bn4Q1X
3-1aCH3HN(CH3)20-1CH3CH31CO2CH3X1
3-1bCH3HN(CH3)20-1CH3CH31CO2CH3X1
3-2aCH3HN(CH3)214 Ph 0--1CO2CH3X1
3-2bCH3HN(CH3)214 Ph0--1CO2CH3X1
3-3aCH3HN(CH3)213 Ph0--1CO2CH3X1
3-3bCH3HN(CH3)213 Ph0--1X1
3-4aCH3HN(CH3)214 Ph1HH1CO2CH3X1
3-4bCH3HN(CH3)214 Ph1HH1CO2CH3X1
3-5aCH3HN(CH3)20-1CH3CH31CH3X1
3-5b CH3HN(CH3)20-1CH3CH31CH3X1
3-6aCH3HN(CH3)214 Ph0--1OtBuX1
3-6bCH3HN(CH3)214 Ph0--1OtBuX1
3-7aCH3HN(CH3)21/td> 4 PhO1HH1CO2CH3X1
3-7bCH3HN(CH3)214 PhO1HH1CO2CH3X1
3-8aCH3HN(CH3)20-2HH1OCH3X1
3-8bCH3HN(CH3)20-2HH 1OCH3X1
3-9aCH3HN(CH3)214 Ph0--1OCH3X1
3-10aCH3HN(CH3)21TRANS
CH=CHPh
0--0-X1
3-10bCH3HN(CH3)21TRANS
CH=CHPh
0--0-X1
3-11aH 3HN(CH3)214 Ph0--1CNX1
3-11bCH3HN(CH3)214 Ph0--1CNX1
3-12aCH3HN(CH3)214 Ph0--1NO2X1
3-13aCH3HN(CH3)20- 1EtEt1CO2EtX1
3-14aCH3HN(CH3)20-1CH2CH2ring1CO2EtX1
3-15aCH3HN(CH3)20-1CH2CH2CH2ring1CO2EtX1
3-16aCH3HN(CH3)20-1CH2CH2OCH2CH2ring 1CO2CH3X1
3-17aCH3HN(CH3)20-1CH2(CH2)3CH2ring1CO2EtX1
3-18aCH3HN(CH3)20-1CH2(CH2)2CH2ring1CO2EtX1
3-19aCH3HN(CH3)21Ph0--0-X1
3-19bCH3HN(CH3)21Ph0--0-X1
3-20aCH3HN(CH2)2O(CH2)2ring0-1CH3CH31CO2CH3X1
3-21aCH3HN(Et)20-1CH3CH31CO2CH3X1
3-22aCH3H N(CH3)cyclo-
hexyl
0-1CH3CH31CO2CH3X1
3-23aCH3HN(CH3)n-butyl0-1CH3CH31CO2CH3X1
3-24aCH3HN(CH3)iPr0-1CH3CH31CO2CH3X1
3-25aCH3HN(CH2)4ring-1CH3CH31CO2CH3X1
3-26aCH3HN(CH3)Et0-1CH3CH31CO2CH3X1
3-27aCH3HN(CH3)20-0--1CO2tBuX1
3-27bCH3HN(CH3)20-0-1CO2tBuX1
3-28CH3CH3N(CH3)20-1CH3CH31CO2CH3X1
3-29HHN(CH3)20-1CH3CH31CO2CH3X1
3-30aA2*1Ph0--0-X1
3-30bA2 1Ph0--0-X1
3-31aCH3HN(CH3)20-1CH2(CH2)2CH2ring1CO2EtX2
3-32aEtHN(CH3)20-1CH3CH31CO2CH3X1
3-33aCH3HN(CH3)iPr0-1 CH2(CH2)2CH2ring1CO2EtX2

in which A2*=R2R3G1taken together with the carbon to which they were attached, form:

in which • denotes the carbon to which they attach.

Method D General synthesis for the preparation of compounds of formula I: Acetonitrile solution (0.2 M) of compounds of formula II (1 EQ.) download 1,1'-carbonyl diimidazol or 1,1-carbonyldiimidazole (2 EQ.) and left to stir at 70°C for 10 hours. The reaction mixture was extinguished with water and saturated NaHCO3and concentrated in vacuo to suspension. The mixture was distributed between CH2Cl2and NaHCO3(feast upon.) and the aqueous layer was extracted with CH2Cl2(5×). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuum. The obtained residue was purified by chromatography on silica gel (gradient 2:1 CH2Cl2:4% CH3OH in CH2Cl2(1% ~ 7h. NH3in CH3OH) 4% CH3OH in CH2Cl2(1% ~ 7h. NH3in CH3OH)to obtain the desired compounds of formula I.

EXAMPLE 3-1A (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4 and R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ of 0.79 (d, 3H,J=and 6.6 Hz), of 1.35 (s, 6H), and 2.27 (s, 6H), 3.46 in-3,55 (m, 1H), 3,70 (s, 3H), 4,07 (s, 2H), of 5.05 (d, 1H,J=a 10.6 Hz), 7,00 (s, 2H), 7,11-7,14 (m, 1H), 7,17 (d, 1H,J=5,2 Hz), 7,26-7,30 (m, 1H), 7,65 (d, 2H,J=to 11.6 Hz), 7,72 (d, 2H,J=8,8 Hz); MS (ES) 410,0 (M+1).

EXAMPLE 3-1b (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ of 0.90 (d, 3H,J=and 6.6 Hz), of 1.35 (s, 6H), of 2.21 (s, 6H), 3,55-3,63 (m, 1H), 3,70 (s, 3H), 4,07 (s, 2H), 5,09 (d, 1H,J=9.8 Hz), 7,01 (d, 2H,J=9.6 Hz), 7,10 (s, 1H), 7,15 (d, 1H,J=the 2.6 Hz), 7,40 (DD, 1H,J=1,4 Hz, 8.6 Hz), to 7.67 -7,71 (m, 4H); MS (ES) 410,0 (M+1).

EXAMPLE 3-2a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl,n3=0, n4=1 and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ 0,81 (d, 3H,J=8.0 Hz), 2,28 (s, 6H), 3,49-of 3.53 (m, 1H), 3,93 (s, 3H), of 5.06 (d, 1H,J=8.0 Hz), of 5.24 (s, 2H), 7,00 (s, 2H), 7,16 (d, 1H,J=2,4 Hz), 7,27-7,31 (m, 2H), 7,55 (d, 2H,J=8.0 Hz ), the 7.65 to 7.75 (m, 4H), 8,07 (d, 2H,J=8.0 Hz); MS (ES) 375,9 (M+1).

EXAMPLE 3-2b (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ of 0.90 (d, 3H,J=8.0 Hz), of 2.23 (s, 6H), to 3.58-3,62 (m, 1H), 3,93 (s, 3H), 5,09 (d, 1H,J=8.0 Hz), of 5.24 (s, 2H), 7,01 (d, 2H,J=8.0 Hz), to 7.15 (d, 1H,J=2.4 Hz), 7.23 percent-of 7.25 (m, 2H), 7,41-the 7.43 (m, 1H), 7,55 (d, 2H,J=8.0 Hz), 7,65-7,74 (m, 3H), 8,07 (d, 2H,J=8.0 Hz); MS (ES) 375,9 (M+1).

EXAMPLE 3-3a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=3-phenyl, n3=0, n4=1, and Q1=CO2CH3): The title compound was obtained which by the above method D total synthesis where used, the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=3-phenyl, n3=0, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ to 0.80 (d, 3H,J=6,6 Hz), 2,28 (s, 6H), 3,47-3,55 (m, 1H), 3,92 (s, 3H), of 5.06 (d, 1H,J=to 10.6 Hz), to 5.21 (s, 2H), 6.75 in (s, 1H), 7,21-7,27 (m, 1H), of 7.36 was 7.45 (m, 3H), to 7.59 (d, 2H,J=7,2 Hz), 7,73-7,87 (m, 4H), to 7.93 (s, 1H), 8,01 (s, 1H); MS (ES) 443,9 (M+1).

EXAMPLE 3-3b (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=3-phenyl, n3=0, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=3-phenyl, n3=0, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ of 0.91 (d, 3H,J=6,6 Hz), of 2.21 (s, 6H), 3,55-the 3.65 (m, 1H), 3,93 (s, 3H), 5,08 (d, 1H,J=10,2 Hz), to 5.21 (s, 2H), 6,83 (s, 1H), 7.23 percent (DD, 1H,J=2,6, 8,8 Hz), 7,37-7,38 (m, 2H), 7,51 (t, 1H,J=7,4 Hz), 7.68 per-to $ 7.91 (m, 7H), with 8.05 (s, 1H); MS (ES) 443,89.

EXAMPLE 3-4a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=1, R4band R5b=H, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)sub> 2, n2=1, Z=4-phenyl, n3=1, R4band R5b=H, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ to 0.80 (d, 3H,J=and 6.6 Hz), 2,28 (s, 6H), 3.43 points-to 3.58 (m, 1H), to 3.64 (s, 2H), 3,70 (s, 3H), of 5.05 (d, 1H,J=10.0 Hz), further 5.15 (s, 2H), 6,99 (s, 2H), 7,17-7,33 (m, 5H), 7,42 (s, 1H), 7,46 (s, 1H), 7,65-7,73 (m, 4H); MS (ES) 458,0 (M+1).

EXAMPLE 3-4b (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=1, R4band R5b=H, n4=1, and Q1=CO2CH3): The title compound was obtained by the above described method C total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=1, R4band R5b=H, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ of 0.90 (d, 3H,J=and 6.6 Hz), of 2.21 (s, 6H), 3,53-the 3.65 (m, 1H), to 3.64 (s, 2H), 3,69 (s, 3H), 5,10 (d, 1H,J=10.0 Hz), further 5.15 (s, 2H), 7,01 (d, 2H,J=4.4 Hz), 7.18 in-7,26 (m, 3H), 7,29 (s, 1H), 7,33 (s, 1H), 7,41 was 7.45 (m, 2H), 7,65-7,73 (m, 4H); MS (ES) 458,0 (M+1).

EXAMPLE 3-5a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CH .1H NMR (CDCl3, 200 MHz) δ to 0.80 (d, 3H,J=6,4 Hz), of 3.69 (s, 9H), of 2.28 (s, 6H), 3,49-of 3.53 (m, 1H), 3,70 (s, 2H), of 5.05 (d, 1H,J=10.4 Hz), 7,00 (d, 2H,J=4,8 Hz), to 7.09 (d, 1H,J=2.0 Hz), 7,19 (DD, 1H,J=2,4 Hz and 8.8 Hz), 7,29 (d, 1H,J=1,6 Hz), 7,63-7,74 (m, 4H); MS (ES) 366,0 (M+1).

EXAMPLE 3-5b (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CH3.1H NMR (CDCl3, 200 MHz) δ of 0.90 (d, 3H,J=6,0 Hz)of 1.07 (s, 9H), 2,12 (s, 6H), 3,57-3,61 (m, 1H), 3,69 (s, 2H), 5,10 (d, 1H,J=10 Hz), 7,00 (SHS, 1H), 7,03 (SHS, 1H), was 7.08 (d, 1H,J=2.0 Hz), 7,17 (DD, 1H,J=2,4 Hz and 9.2 Hz), 7,40 (DD, 1H,J=1,0, 4,2 Hz), 7,66-of 7.70 (m, 4H); MS (ES) 366,02 (M+1).

EXAMPLE 3-6a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=OtBu): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=OtBu.1H NMR (CDCl3, 200 MHz) δ 0,81 (d, 3H,J=6,0 Hz)of 1.36 (s, 9H), of 2.21 (s, 6H), 3,47-3,63 (m, 1H), 5,06 (d 1H, J=6,0 Hz), 5,11 (s, 2H), 7,00? 7.04 baby mortality (m, 4H), 7,19-7,39 (m, 5H), to 7.64-7,74 (m, 4H); MS (ES) 458,0 (M+1).

EXAMPLE 3-6b (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=OtBu): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=OtBu.1H NMR (CDCl3, 200 MHz) δ of 0.91 (d, 3H,J=6,0 Hz)of 1.36 (s, 9H), of 2.21 (s, 6H), 3,47-3,63 (m, 1H), is 5.06 (d, 1H,J=6,0 Hz), 5,11 (s, 2H), 7,00? 7.04 baby mortality (m, 4H), 7,19-7,39 (m, 5H), to 7.64-7,74 (m, 4H); MS (ES) 458,0 (M+1).

EXAMPLE 3-7a (a compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-PhO, n3=1, R4band R5b=H, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-PhO, n3=1, R4band R5b=H, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ to 0.80 (d, 3H,J=6,6 Hz), 2,73 (s, 6H), 3.46 in-3,55 (m, 1H), 3,80 (s, 3H), with 4.64 (s, 2H), of 5.05 (d, 1H,J=to 10.6 Hz), 5,09 (s, 2H), 6.90 to-7,00 (m, 4H), 7,17-7,31 (m, 2H), was 7.36-7,44 (m, 3H), of 7.64-7,73 (m, 4H); MS (ES) 474,0 (M+1).

EXAMPLE 3-7b (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2 , n2=1, Z=4-PhO, n3=1, R4band R5b=H, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-PhO, n3=1, R4band R5b=H, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 200 MHz) δ of 0.89 (d, 3H,J=6,6 Hz), 2,73 (s, 6H), 3.46 in-3,55 (m, 1H), 3,80 (s, 3H), with 4.64 (s, 2H), of 5.05 (d, 1H,J=to 10.6 Hz), 5,09 (s, 2H), 6.90 to-7,00 (m, 4H), 7,17-7,31 (m, 2H), was 7.36-7,44 (m, 3H), of 7.64-7,73 (m, 4H); MS (ES) 474,0 (M+1).

EXAMPLE 3-8a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=2, R4band R5b=H, n4=1, and Q1=OCH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=2, R4band R5b=H, n4=1, and Q1=OCH3. MS (ES) 354,3 (M+1).

EXAMPLE 3-8b (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=2, R4band R5b=H, n4=1, and Q1=OCH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=2, R4band R5b=H, n4=1, and Q1 =OCH3. MS (ES) 354,3 (M+1).

EXAMPLE 3-9a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=OCH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=OCH3. MS (ES) 416,3 (M+1).

EXAMPLE 3-10a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=corresponds to TRANS-CH=CHPh, n3 and n4=0): is Specified in the title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=corresponds to TRANS-CH=CHPh, n3 and n4=0. MS (ES) 412,3 (M+1).

EXAMPLE 3-10b (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=corresponds to TRANS-CH=CHPh, n3 and n4=0): is Specified in the title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=corresponds to TRANS-CH=CHPh, n3 and n4=0. MS (ES) 412,3 (M+1).

EXAMPLE 3-11a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CHsub> 3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=CN): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=CN.1H NMR (CDCl3, 400 MHz) δ to 0.80 (d, 3H,J=6,4 Hz), 2,28 (s, 6H), 3,48-of 3.53 (m, 1H), is 5.06 (d, 1H,J=10.4 Hz), of 5.24 (s, 2H), 7,00 (s, 2H), 7,14 (d, 1H,J=2,4 Hz), 7,24 (d, 1H,J=2,4 Hz), 7,29-7,31 (m, 1H), to 7.59 (d, 2H,J=8,4 Hz), a 7.62 (d, 2H, J=2.4 Hz), 7,69 (d, 2H,J=1,6 Hz), 7,71-7,76 (m, 2H).

EXAMPLE 3-11b (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=CN): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=CN.1H NMR (CDCl3, 400 MHz) δ of 0.91 (d, 3H,J=6,4 Hz), 2,22 (s, 6H), to 3.58-3,63 (m, 1H), 5,10 (d, 1H,J=10.0 Hz), 5,28 (s, 2H), 7,01 (d, 2H,J=12.0 Hz), 7,14 (s, 1H), 7.23 percent (s, 1H), 7,43 (d, 1H,J=8,8 Hz) of 7.64-7,76 (m, 6H), compared to 8.26 (d, 2H,J=7,2 Hz).

EXAMPLE 3-12a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=NO2): The title compound was obtained by the above method D total synthesis, which used compounds is their formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, n4=1, and Q1=NO2.1H NMR (CDCl3, 400 MHz) δ to 0.80 (d, 3H,J=6,4 Hz), 2,28 (s, 6H), 3,48-of 3.53 (m, 1H), is 5.06 (d, 1H,J=10.4 Hz), of 5.24 (s, 2H), 7,13 (s, 1H), 7,22 (DD, 1H,J=2,4, 8,8 Hz), 7,42 (d, 1H,J=8,4 Hz), EUR 7.57-to 7.59 (m, 2H), to 7.67 to 7.75 (m, 8H).

EXAMPLE 3-13a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH2CH3, n4=1, and Q1=CO2Et): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH2CH3, n4=1, and Q1=CO2Et. MS (ES) 452,3 (M+1).

EXAMPLE 3-14a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopropyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopropyl, n4=1, and Q1=CO2Et. THE (ES) 422,3 (M+1).

EXAMPLE 3-15a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclobutyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclobutyl, n4=1, and Q1=CO2Et. MS (ES) 436,3 (M+1).

EXAMPLE 3-16a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring of 4-pyranyl, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring of 4-pyranyl, n4=1, and Q1=CO2CH3. MS (ES) 452,3 (M+1).

EXAMPLE 3-17a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3 2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a cyclohexyl ring, n4=1, and Q1=CO2Et): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a cyclohexyl ring, n4=1, and Q1=CO2Et. MS (ES) 464,2 (M+1).

EXAMPLE 3-18a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et. MS (ES) 450,3 (M+1).

EXAMPLE 3-19a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=Ph, n3 and n4=0): is Specified in the title compound was obtained by the above method D total synthesis, was cotransporter compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=Ph, n3 and n4=0.1H NMR (CDCl3, 200 MHz) δ to 0.80 (d, 3H,J=6,0 Hz), of 2.21 (s, 6H), 3,47-3,55 (m, 1H), to 5.03 (d, 1H,J=6,0 Hz)to 5.17 (s, 2H), 7,00-7,74 (m, 14H); MS (ES) 386,1 (M+1).

EXAMPLE 3-19b (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=Ph, n3 and n4=0): is Specified in the title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=Ph, n3 and n4=0.1H NMR (CDCl3, 200 MHz) δ of 0.91 (d, 3H,J=6,0 Hz), of 2.21 (s, 6H), 3,47-3,55 (m, 1H), to 5.03 (d, 1H,J=6,0 Hz)to 5.17 (s, 2H), 7,00-7,74 (m, 14H); MS (ES) 386,1 (M+1).

EXAMPLE 3-20a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH2)2O(CH2)2-ring, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH2)2O(CH2)2-ring, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3. MS (ES) 452,3 (M+1).

EXAMPLE 3-21a (a compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(Et)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q 1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(Et)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3. MS (ES) 438,3 (M+1).

EXAMPLE 3-22a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)-cyclohexyl, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)-cyclohexyl, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3. MS (ES) 478,2 (M+1).

EXAMPLE 3-23a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)-n-butyl, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)-n-butyl, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3. MS (ES) 425,2 (M+1).

EXAMPLE 3-24a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(H 3)iPr, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)iPr, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3. MS (ES) 438,2 (M+1).

EXAMPLE 3-25a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH2)4, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH2)4, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3. MS (ES) 436,3 (M+1).

EXAMPLE 3-26a (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)Et, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)Et, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3. MS (ES) 424,3 (M+1).

EXAMPLE 3-27a (compound of formula I where X1=imidazol-1-yl, R2=CH 3, R3=H, G1=N(CH3)2, n2=0, n3=0, n4=1, and Q1=CO2tBu): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=0, n4=1, and Q1=CO2tBu.1H NMR (CDCl3, 200 MHz) δ of 0.79 (d, 3H,J=6,6 Hz), for 1.49 (s, 9H), and 2.27 (s, 6H), 3,51-3,66 (m, 1H), br4.61 (s, 2H), 5,20 (d, 1H,J=4.0 Hz), 6,98? 7.04 baby mortality (m, 3H), 7,21 (DD, 1H,J=2,6, 9,2 Hz), 7,41 (DD, 1H,J=1,8, and 8.4 Hz), of 7.64-7,74 (m, 4H).

EXAMPLE 3-27b (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=0, n4=1, and Q1=CO2tBu): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=0, n4=1, and Q1=CO2tBu.1H NMR (CDCl3, 200 MHz) δ of 0.89 (d, 3H,J=6,6 Hz), for 1.49 (s, 9H), of 2.20 (s, 6H), 3,51-3,66 (m, 1H), br4.61 (s, 2H), ceiling of 5.60 (d, 1H,J=9.4 Hz), 6,98? 7.04 baby mortality (m, 3H), 7,21 (DD, 1H,J=2,6, 9,2 Hz), 7,41 (DD, 1H,J=1,8, and 8.4 Hz), of 7.64-7,74 (m, 4H).

EXAMPLE 3-28 (compound of formula I where X1=imidazol-1-yl, R2=CH3, R3=CH3, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, in which the use is ovali compound of formula II, R2=CH3, R3=CH3, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3. MS (ES) 424,3 (M+1).

EXAMPLE 3-29 (compound of formula I where X1=imidazol-1-yl, R2=H, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=H, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3.1H NMR (CDCl3, 400 MHz) δ of 1.36 (s, 6H), 2,31 (s, 6H), 2.91 in-3,19 (m, 2H), 3,70 (s, 3H), 4,08 (s, 2H), 5,39-5,42 (m, 1H), 7,00-of 7.23 (m, 5H), 7,55 (s, 1H), 7,66-of 7.70 (m, 3H); MS (ES) 396,0 (M+1).

EXAMPLE 3-30a (compound of formula I where X1=imidazol-1-yl, R2, R3and G1taken together correspond A2*(see Table 3), n2=1, Z=Ph, and n3 and n4=0): is Specified in the title compound was obtained by the above method D total synthesis, which used the compound of formula II, X1=imidazol-1-yl, R2, R3and G1taken together correspond A2*, n2=1, Z=Ph, and n3 and n4=0. White substance, melting point 124-s; MS (ES) 398,18 (M+1).

EXAMPLE 3-30b (compound of formula I where X1=imidazol-1-yl, R2, R3and G1taken together correspond A2*(see Table 3), n2=1, Z=Ph): pointed to by the e in the title compound was obtained by the above method D total synthesis where used, the compound of formula II, X1=imidazol-1-yl, R2, R3and G1taken together correspond A2*, n2=1, Z=Ph. White substance, the melting point of 110-112°C.; MS (ES) 398,05 (M+1).

EXAMPLE 3-31a (compound of formula I in which x2=triazole-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et. MS (ES) 451,2 (M+1).

EXAMPLE 3-32a (compound of formula I where X1=imidazol-1-yl, R2=CH2CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH2CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CO2CH3. MS (ES) 424,2 (M+1).1H NMR (CDCl3, 400 MHz) δ of 0.74 (t, 3H,J=the 7.4 Hz), 1,1-of 1.27 (m, 1H), 1,36 (s, 6H), 1,45-of 1.56 (m, 1H), 2,33 (s, 6H), 3.25 to and 3.31 (m, 1H), 3,70 (s, 3H), 4,07 (s, 2H), 5,12 (d, 1H,J=10,0 Hz), 7,00 (s, 1H), 7,05 (s, 1H), 7,11 (d, 1H,J=2.3 Hz), 7,16 (DD, 1H,J=of 2.5 to 8.9 Hz), 7,37 (DD, 1H,J=a 1.8, 8.5 Hz), 7.68 per-of 7.70 (m, 4H).

EXAMPLE 3-33a (compound of formula I in which x2=triazole-1-yl, R2=CH3, R3=H, G1=N(CH3)iPr, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et): The title compound was obtained by the above method D total synthesis, which used the compound of formula II, R2=CH3, R3=H, G1=N(CH3)iPr, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, n4=1, and Q1=CO2Et. MS (ES) 478,2 (M+1).

Following the General methods described above, were obtained the following compounds of formula I-B, which are shown in table 4. In the rooms of the examples of "a" indicates SYN-isomer, and "b" denotes the anti-isomer relative to X and G1. X1=imidazol-1-yl, x2=triazole-1-yl and X3=triazole-3-yl.

-
Table 4
The list of compounds of formula I-B
ExampleR2 R3G1n2Zn3R4bR5bX
4-1aCH3HN(CH3)20-1CH3CH3X1
4-1bCH3HN(CH3)20-1CH3CH3X1
4-2aCH3HN(CH3)214 Ph0--X1
4-2bCH3H N(CH3)214 Ph0--X1
4-3aCH3HN(CH3)213 Ph0--X1
4-3bCH3HN(CH3)213 Ph0--X1
4-4aCH3HN(CH3)214 Ph1HHX1
4-4bCH3HN(CH3)21 4 Ph1HHX1
4-5aCH3HN(CH3)20-1EtEtX1
4-6aCH3HN(CH3)20-1CH2CH2ringX1
4-7aCH3HN(CH3)20-1CH2CH2CH2ringX1
4-8aCH3HN(CH3)20-1 CH2CH2OCH2CH2ringX1
4-9aCH3HN(CH3)20-1CH2(CH2)3CH2ringX1
4-10aCH3HN(CH3)20-1CH2(CH2)2CH2ringX1
4-11aCH3HN(CH2)2O(CH2)2ring0-1CH3CH3X1
4-12aCH3HN(Et)201CH3CH3X1
4-13aCH3HN(CH3)cyclo-
hexyl
0-1CH3CH3X1
4-14aCH3HN(CH3)n-butyl0-1CH3CH3X1
4-15aCH3HN(CH3)iPr0-1CH3CH3X1
4-16aCH3HN(CH2)4ring0 -1CH3CH3X1
4-17aCH3HN(CH3)Et0-1CH3CH3X1
4-18CH3CH3N(CH3)20-1CH3CH3X1
4-19HHN(CH3)20-1CH3CH3X1
4-20aCH3HN(CH3)20- 1CH2(CH2)2CH2ringX2
4-21aEtHN(CH3)20-1CH3CH3X1
4-22aCH3HN(CH3)iPr0-1CH2(CH2)2CH2ringX1

Method E General synthesis for the preparation of compounds of formula I-B: a Solution of the compounds of formula I-C in THF were loaded with 5 equivalents of NaOH in H2O and left to stir at 45°C for 3 hours. The reaction mixture was concentrated in vacuo to solids, made in a minimum amount of water, neutralized to pH 7 6M HCl and was extracted with CH2Cl2. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuum. The obtained solids eyes is Ali by chromatography on silica gel with 10% CH 3OH in CHCl3to obtain the desired compounds of formula I-B.

EXAMPLE 4-1a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3and R7=CH3.1H NMR (CD3OD, 200 MHz) δ of 0.85 (d, 3H,J=6,6 Hz), 1,32 (s, 6H), is 2.30 (s, 6H), 3,81-3,98 (m, 1H), 4,07 (s, 2H), 5,43 (d, 1H,J=15 Hz), 6,97-7,22 (m, 3H), 7,35-of 7.60 (m, 2H), 7.23 percent-of 7.96 (m, 3H), to 8.20 (s, 1H); MS (ES) 395,9 (M+1).

EXAMPLE 4-1b (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3and R7=CH3.1H NMR (CD3OD, 200 MHz) δ were 0.94 (d, 3H,J=6,6 Hz), 1,32 (s, 6H), is 2.30 (s, 6H), 3,81-3,98 (m, 1H), 4,07 (s, 2H), 6,97-7,22 (m, 3H), 7,35-of 7.60 (m, 2H), 7.23 percent-of 7.96 (m, 3H), to 8.20 (s, 1H); MS (ES) 395,9 (M+1).

EXAMPLE 4-2a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3) 2, n2=1, Z=4-phenyl, and n3=0): is Specified in the title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, and R7=CH3.1H NMR (DMSO-d6, 400 MHz) δ of 0.85 (d, 3H,J=8.0 Hz), 2,39 (s, 6H), 4,15-and 4.40 (m, 1H), 5,31 (s, 2H), of 5.83 (d, 1H,J=9,2 Hz), 7,30 (DD, 1H,J=9,2 Hz, 2.8 Hz), to 7.15 (d, 1H,J=2.0 Hz), to 7.59 (d, 2H,J=8,4 Hz), to 7.67 (d, 2H,J=8,8 Hz), 8,31 (d, 2H,J=8,8 Hz), to $ 7.91-of 7.96 (m, 3H), with 8.05 (s, 1H), 9,05 (s, 1H); MS (ES) 429,1 (M+1).

EXAMPLE 4-2b (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, and n3=0): is Specified in the title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=0, and R7=CH3.1H NMR (CD3OD, 200 MHz) δ of 0.71 (d, 3H,J=6,4 Hz), 2,10 (s, 6H), 3,74-3,82 (m, 1H), 5,27 (s, 2H), of 5.34 (d, 1H,J=to 11.0 Hz), PC 6.82 (s, 1H), 7.23 percent (DD, 1H,J=9,2 Hz, 2.6 Hz), of 7.36-7,39 (m, 2H), 7,55 (d, 2H,J=8.0 Hz), 7,69 (d, 2H,J=3.8 Hz), 7,75-7,80 (m, 2H), to $ 7.91-to 7.95 (m, 3H); MS (ES) 361,8 (M+1).

EXAMPLE 4-3a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=3-phenyl and n3=0): is Specified in the title compound was obtained by the above described method E about the future of synthesis, where used, the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=3-phenyl, n3=0, and R7=CH3.1H NMR (CDCl3, 200 MHz) δ of 0.66 (d, 3H,J=6.2 Hz), of 2.15 (s, 6H), 3,65-a 3.83 (m, 1H), 5,24 (s, 2H), 5,33 (d, 1H,J=to 11.4 Hz), 6.75 in (s, 1H), 6.75 in (s, 1H), 7,21-7,27 (m, 1H), 7,34 was 7.45 (m, 3H), to 7.59 (d, 2H,J=7,2 Hz), 7,73-7,87 (m, 4H), to 7.93 (s, 1H), 8,01 (s, 1H); MS (ES) 430,0 (M+1).

EXAMPLE 4-3b (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=3-phenyl and n3=0): is Specified in the title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=3-phenyl, n3=0, and R7=CH3.1H NMR (CDCl3, 200 MHz) δ of 0.71 (d, 3H,J=6.2 Hz), is 2.09 (s, 6H), 3,74-a 3.83 (m, 1H), 5,28 (s, 2H), of 5.34 (d, 1H,J=to 11.4 Hz), 6,83 (s, 1H), 7,21 (d, 1H,J=the 2.6 Hz), 7,25 (d, 1H,J=the 2.6 Hz), 7,37-to $ 7.91 (m, 9H), with 8.05 (s, 1H); MS (ES) 430,0 (M+1).

EXAMPLE 4-4a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=1 and R4band R5b=H): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=1, R4band R5b=H and R7 3.1H NMR (CDCl3, 400 MHz) δ of 0.77 (d, 3H,J=6.2 Hz), 2,19 (s, 6H), 3.46 in-3,70 (m, 3H), 5,00-by 5.18 (m, 3H), 7,02 (m, 2H), 7,15 and 7.36 (m, 6H), 7,62-of 7.69 (m, 3H), 7,89 (s, 1H), 8,08 (s, 1H), of 11.26 (SHS, 1H).

EXAMPLE 4-4b (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=1 and R4band R5b=H): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-phenyl, n3=1, R4band R5b=H and R7=CH3.1H NMR (CDCl3, 400 MHz) δ of 0.90 (d, 3H), 2,24 (s, 6H), 3.46 in-3,70 (m, 3H), 5,00-by 5.18 (m, 3H), 7,02 (m, 2H), 7,15 and 7.36 (m, 6H), 7,62-of 7.69 (m, 3H), 7,89 (s, 1H), 8,08 (s, 1H), of 11.26 (SHS, 1H).

EXAMPLE 4-5a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1 and R4band R5b=CH2CH3): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH2CH3and R7=Et. MS (ES) 424,2 (M+1).

EXAMPLE 4-6a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1 and R4band R5btaken together with the carbon to which the WMD they were annexed, make ring cyclopropyl): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopropyl and R7=Et. MS (ES) 394,2 (M+1).

EXAMPLE 4-7a (a compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1 and R4band R5btaken together with the carbon to which they were attached, form a ring cyclobutyl): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclobutyl and R7=Et. MS (ES) 408,6 (M+1).

EXAMPLE 4-8a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1 and R4band R5btaken together with the carbon to which they were attached, form a ring of 4-pyranyl): The title compound was obtained by the above described method E total synthesis, which used the connection fo the mules I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring of 4-pyranyl and R7=CH3. MS (ES) 438,3 (M+1).

EXAMPLE 4-9a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1 and R4band R5btaken together with the carbon to which they were attached, form a cyclohexyl ring): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a cyclohexyl ring, and R7=Et. MS (ES) 436,2 (M+1).

EXAMPLE 4-10a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1 and R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they process Denali, make the ring cyclopentyl and R7=Et. MS (ES) 422,2 (M+1).

EXAMPLE 4-11a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH2)2O(CH2)2-ring, n2=0, n3=1 and R4band R5b=CH3): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH2)2O(CH2)2-ring, n2=0, n3=1, R4band R5b=CH3and R7=CH3.1H NMR (CD3OD, 400 MHz) δ to 0.92 (d, 3H,J=6,8 Hz)of 1.36 (s, 6H), 2,45-2,52 (m, 2H), 2,75 is 2.80 (m, 2H), 3,48 at 3.69 (m, 4H), 3,69-to 3.73 (m, 1H), 4,12 (s, 2H), 5,42 (d, 1H,J=the 11.6 Hz), 6,99-7,00 (m, 1H), 7,18 (DD, 1H, J=9,2 Hz, 3.2 Hz), 7,25 (d, 1H,J=4.0 Hz), of 7.36-7,39 (m, 1H), 7,55 (d, 1H,J=9,2 Hz), 7,73-7,83 (m, 2H), 7,89 (s, 1H), 8,04 (s, 1H).

EXAMPLE 4-12a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(Et)2, n2=0, n3=1 and R4band R5b=CH3): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(Et)2, n2=0, n3=1, R4band R5b=CH3and R7=CH3.1H NMR (CD3OD, 400 MHz) δ of 0.85 (d, 3H,J=6,8 Hz)of 0.93 (t, 6H,J=6,8 Hz)to 1.37 (s, 6H), 2,37 at 2.45 (m, 2H), 2,65-by 2.73 (m, 2H), 3,76-a-3.84 (m, 1H), 4.09 to (s, 2H), 5,35 (d, 1H,J=11.2 Hz), 7,0 (, 1H), 7,15 (DD, 1H,J=9,2 Hz, 2.4 Hz), 7.23 percent (d, 1H,J=2.0 Hz), 7,37 (s, 1H), 7,56 (d, 1H,J=8,4 Hz), to 7.77 (m, 2H), of 7.90 (s, 1H), 8,11 (s, 1H).

EXAMPLE 4-13a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)-cyclohexyl, n2=0, n3=1 and R4band R5b=CH3): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)-cyclohexyl, n2=0, n3=1, R4band R5b=CH3and R7=CH3. MS (ES) 464,2 (M+1).

EXAMPLE 4-14a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)-n-butyl, n2=0, n3=1 and R4band R5b=CH3): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)-n-butyl, n2=0, n3=1, R4band R5b=CH3and R7=CH3. MS (ES) 438,1 (M+1).

EXAMPLE 4-15a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)iPr, n2=0, n3=1 and R4band R5b=CH3): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(H 3)iPr, n2=0, n3=1, R4band R5b=CH3and R7=CH3. MS (ES) 424,2 (M+1).

EXAMPLE 4-16a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH2)4-ring, n2=0, n3=1 and R4band R5b=CH3): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH2)4-ring, n2=0, n3=1, R4band R5b=CH3and R7=CH3. MS (ES) 436,3 (M+1). MS (ES) 422,1 (M+1).

EXAMPLE 4-17a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)Et, n2=0, n3=1 and R4band R5b=CH3): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)Et, n2=0, n3=1, R4band R5b=CH3and R7=CH3.1H NMR (CD3OD, 400 MHz) δ of 0.83 (d, 3H,J=6,8 Hz)to 0.96 (t, 3H,J=6,8 Hz), 1,32 (s, 6H), of 2.28 (s, 3H), 2,42-2,47 (m, 1H), 2,60-to 2.65 (m, 1H), 3,79-3,82 (m, 1H), 4,08 (s, 2H), 5,39 (d, 1H,J=to 10.8 Hz), of 6.99 (s, 1H), 7,14 (DD, 1H,J=9,2 Hz, 2.4 Hz), 7,22 (d, 1H,J=2.0 Hz), was 7.36 (s, 1H), 7,50 (d, 1H,J=8,8 Hz), 7,73-to 7.77 (m, 2H), 7,86 (s, 1H), 8,11 (s, 1H).

EXAMPLE 4-18 (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=CH3, G1=N(CH3 )2, n2=0, n3=1 and R4band R5b=CH3): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=CH3, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3and R7=CH3. MS (ES) 410,2 (M+1).

EXAMPLE 4-19 (compound of formula I-B where X1=imidazol-1-yl, R2=H, R3=H, G1=N(CH3)2, n2=0, n3=1 and R4band R5b=CH3): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=H, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3and R7=CH3.1H NMR (CDCl3, 400 MHz) δ of 1.37 (s, 6H), to 2.29 (s, 6H), 2,99-3,20 (m, 2H), 4,06 (s, 2H), 5,44 (m, 1H), 7,05-7,21 (m, 5H), 7,44-7,52 (m, 2H), 7,63 (d, 1H,J=8,4 Hz), 7,74 (s, 1H); MS (ES) 382,0 (M+1).

EXAMPLE 4-20a (compound of formula I-B where x2=triazole-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1 and R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X2=triazole-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0,n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl and R7=Et. MS (ES) 423,3 (M+1).

EXAMPLE 4-21a (a compound of formula I-B where X1=imidazol-1-yl, R2=CH2CH3, R3=H, G1=N(CH3)2, n2=0, n3=1 and R4band R5b=CH3): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH2CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3and R7=CH3.1H NMR (CDCl3, 400 MHz) δ to 0.72 (t, 3H,J=the 7.4 Hz), 1,19-of 1.26 (m, 1H), 1,38 (s, 6H), 1,47-and 1.54 (m, 1H), 2,32 (s, 6H), 3,26-of 3.31 (m, 1H), 4,08 (m, 2H), 5,08 (d, 1H,J=the 10.1 Hz),? 7.04 baby mortality (d, 2H,J=8,2 Hz), to 7.09 (d, 1H,J=2.3 Hz), 7,13 (DD, 1H,J=2,4, and 8.9 Hz), 7,30 (DD, 1H,J=1,6 Hz, 8.6 Hz), a 7.62 (t, 3H,J=of 11.0 Hz), to 7.84 (s, 1H).

EXAMPLE 4-22a (compound of formula I-B where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)iPr, n2=0, n3=1 and R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl): The title compound was obtained by the above described method E total synthesis, which used the compound of formula I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)iPr, n2=0, n3=1, R4band R5btaken together with the carbon to which their PR is connected, make the ring cyclopentyl and R7=Et. MS (ES) 450,2 (M+1).

Following the General methods described above, were obtained the following compounds of formula I-(HA6)n7(in which R1=H, Y=O, n1=1, R4aand R5a=H, R6aand R6b=H, n4=1), which are given in table 5. In the rooms of EXAMPLE "a" indicates SYN-isomer, and "b" denotes the anti-isomer relative to X and G1. X1=imidazol-1-yl, x2=triazole-1-yl and X3=triazole-3-yl.

CH3
Table 5
The list of compounds of the formula I-(HA6)n7
ExampleR2R3G1n2Zn3R4bR5bQ1X(HA6)n7
5-1aCH3HN(CH3)20-1CH3CO2HX1HCO2H
5-1a'CH3HN(CH3)20-1CH3CH3CO2HX1(HCl)2
5-1bCH3HN(CH3)20-1CH3CH3CO2HX1HCO2H
5-2aCH3HN(CH3)214 Ph1HHCO2 HX1HCO2H
5-3aCH3HN(CH3)20-1EtEtCO2HX1(HCl)2
5-4aCH3HN(CH3)20-1CH2CH2ringCO2HX1(HCl)2
5-5aCH3HN(CH3)20-1CH2CH2CH2ringCO2HX1(HCl)2
5-6a CH3HN(CH3)20-1CH2CH2OCH2CH2ringCO2HX1(HCl)2
5-7aCH3HN(CH3)20-1CH2(CH2)3CH2ringCO2HX1(HCl)2
5-8aCH3HN(CH3)20-1CH2(CH2)2CH2ringCO2HX1(HCl)2
5-9aCH3HN(CH3 )iPr0-1CH2(CH2)2CH2ringCO2HX1(HCl)2
5-10aCH3HN(Et)20-1CH3CH3CO2HX1(HCl)2
5-11aCH3HN(CH3)cyclo-hexyl0-1CH3CH3CO2HX1(HCl)2
5-12aCH3HN(CH3)n-butyl01CH3CH3CO2HX1(HCl)2
5-13aCH3HN(CH3)iPr0-1CH3CH3CO2HX1(HCl)2
5-14aCH3HN(CH3)Et0-1CH3CH3CO2HX1(HCl)2
5-15aCH3HN(CH3)214 PhO1H HCO2HX1HCO2H
5-16aCH3HN(CH3)20-0--CO2HX1(HCl)2
5-16bCH3HN(CH3)20-0--CO2HX1(HCl)2
5-17CH3CH3N(CH3)20-1CH3CH3CO2HX15-18aCH3HN(CH3)20-1CH3CH3CONH2X1HCO2H
5-19aCH3HN(CH3)20-1CH3CH3CONHCH3X1HCO2H
5-20aCH3HN(CH3)20-1CH3CH3CON(CH3)2X1HCO2H
5-21aHN(CH3)214 Ph0--CONH2X1HCO2H
5-22aCH3HN(CH3)214 Ph0--CONH CH3X1HCO2H
5-23aCH3HN(CH3)214 Ph0--CON(CH3)2X1HCO2H
5-24aEtHN(CH3)2 0-1CH3CH3CO2HX1(HCl)2
5-25aCH3HN(CH3)214 Ph0--OHX1HCO2H

Method F General synthesis for the preparation of compounds of the formula I-(HA6)n7: To compounds of formula I was added 5 equivalents of 2 N. HCl in water and the mixture was concentrated in vacuo to solids, to obtain the compounds of formula I-(HCl)2. The compounds of formula I can also be treated with formic acid in water, followed by concentration in vacuum to obtain the compounds of formula I-(HCO2H). In addition to the compounds of formula I was added 3 equivalents of 2 N. HCl in simple ether and concentrated in vacuo to solids, to obtain the compounds of formula I-(HCl)2.

EXAMPLE 5-1a (a compound of the formula I-(HA6)n7in which X1=imide is evil-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1 and R4band R5b=CH3, Q1=CO2H and (HA6)n7=HCO2H): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3and Q1=CO2H.1H NMR (CD3OD, 200 MHz) δ of 0.89 (d, 3H,J=6,6 Hz)of 1.33 (s, 6H), of 2.38 (s, 6H), 3,86-4,01 (m, 1H), 4.09 to (s, 2H), 5,42 (d, 1H,J=of 11.0 Hz), 7,11-8,46 (m, 9H); MS (ES) 396,0 (M+1).

EXAMPLE 5-1a' (a compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1 and R4band R5b=CH3, Q1=CO2H and (HA6)n7=(HCl)2): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3and Q1=CO2H.1H NMR (CD3OD, 400 MHz) δ is 1.31 (d, 3H,J=6,7 Hz)to 1.37 (s, 6H), 3,03 (s, 3H), 3,11 (s, 3H), 4,14 (s, 2H), 5,04-5,12 (m, 1H), 6,28 (d, 1H,J=11.3 Hz), 7,26 (DD, 1H,J=the 2.4 Hz, 9.0 Hz), 7,32 (d, 1H,J=the 2.2 Hz), 7,66 (DD, 1H,J=1.9 Hz, 8.7 Hz), 7,73 (t, 1H,J=the 1.7 Hz), 7,87 (d, 1H,J=9.0 Hz), of 3.94 (d, 1H,J=8.6 Hz), 8,10 (s, 1H), 8,21 (t, 1H,J=1,8 Hz), 9,62 (s, 1H).

EXAMPLE 1b (compound of the formula I-(HA 6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1 and R4band R5b=CH3, Q1=CO2H and (HA6)n7=HCO2H): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3and Q1=CO2H.1H NMR (CD3OD, 200 MHz) δ of 0.93 (d, 3H,J=6,6 Hz)of 1.33 (s, 6H), is 2.30 (s, 6H), 3,91-4,00 (m, 1H), 4.09 to (s, 2H), 5,42 (d, 1H,J=a 10.6 Hz), of 6.96 (s, 1H), 7,14 (DD, 1H,J=2,6 Hz, 9.1 Hz), 7,22 (d, 1H,J=the 2.6 Hz), 7,35 (s, 1H), 7,58-7,94 (m, 5H); MS (ES) 395,9 (M+1).

EXAMPLE 5-2a (compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-Phenyl, n3=1 and R4band R5b=H, Q1=CO2H and (HA6)n7=HCO2H): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-Phenyl, n3=1, R4band R5b=H and Q1=CO2H.1H NMR (CD3OD, 200 MHz) δ of 0.93 (d, 3H,J=6,6 Hz), 2,42 (s, 6H), 3,90-to 3.99 (m, 1H), of 4.54 (s, 2H), 5,14 (s, 2H), 5,52 (d, 1H,J=11.2 Hz), 6,97 (d, 2H,J=8,4 Hz), 6.90 to (d, 1H,J=1.4 Hz), 7,25 (DD, 1H,J=2,6 Hz and 6.6 Hz), 7,33-the 7.43 (m, 3H), 7,50-7,58 (m, 2H), 7,81 (d,2H, J=8,8 Hz), of 7.90-to 7.95 (m, 1H), of 8.37 (s, 1H), 8,44 (s, 1H); MS (ES) 460,0 (M+1).

EXAMPLE 5-3a (compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH2CH3, Q1=CO2H and (HA6)n7=(HCl)2): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH2CH3and Q1=CO2H.1H NMR (CD3OD, 400 MHz) δ of 0.89 (t, 6H,J=a 7.6 Hz)of 1.29 (d, 3H,J=the 6.8 Hz), 1,81 (kV 4H,J=a 7.6 Hz), 3,01 (s, 3H), to 3.09 (s, 3H), 3,30 (s, 2H), 5,06-5,11 (m, 1H), 6,28 (d, 1H,J=11.2 Hz), 7.23 percent (DD, 1H,J=2,8, 9,2 Hz), 7,34 (d, 1H,J=2.0 Hz), to 7.67 (t, 2H,J=of 12.4 Hz), the 7.85 (d, 1H,J=9,2 Hz), to 7.93 (d, 1H,J=8,8 Hz), 8,10 (s, 1H), to 8.20 (s, 1H), 9,62 (s, 1H).

EXAMPLE 5-4a (compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopropyl, Q1=CO2H and (HA6)n7=(HCl)2): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(C 3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopropyl and Q1=CO2H.1H NMR (DMSO-d6, 400 MHz), δ 1,15-of 1.18 (m, 2H), 1,20 (d, 3H,J=a 6.5 Hz), 1,33-of 1.36 (m, 2H), 2.91 in (s, 3H), to 3.02 (s, 3H), 4,29 (s, 2H), 5,24 to 5.35 (m, 1H), 6,51 (d, 1H,J=11.3 Hz), was 7.36 (DD, 1H,J=of 2.5 to 8.9 Hz), was 7.45 (d, 1H,J=the 2.4 Hz), the 7.85-7,86 (m, 2H), 7,92 (d, 1H,J=9.1 Hz), 8,00 (d, 1H,J=the 8.9 Hz), 8,24 (s, 1H), 8,39 (s, 1H), becomes 9.97 (s, 1H), accounted for 10.39 (s, 1H).

EXAMPLE 5-5a (a compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclobutyl, Q1=CO2H and (HA6)n7=(HCl)2): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclobutyl and Q1=CO2H.1H NMR (DMSO-d6, 400 MHz), δ is 1.10 (d, 3H,J=to 7.61), 1,85 is 2.10 (m, 4H), 2,37 at 2.45 (m, 2H), 2,82 (s, 3H), of 2.92 (s, 3H), 4,33 (s, 2H), 5,23 at 5.27 (m, 1H), 6,46 (d, 1H,J=of 11.0 Hz), 7.23 percent (DD, 1H,J=of 2.5, 9.0 Hz), 7,44 (d, 1H,J=the 2.4 Hz), of 7.75 (s, 1H), 7,78-7,83 (m, 2H), to $ 7.91 (d, 1H,J=to 8.7 Hz), 8,17 (s, 1H), with 8.33 (s, 1H), to 9.93 (s, 1H), 10,36 (s, 1H).

EXAMPLE 5-6a (Obedinenie formula I-(HA 6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring of 4-pyranyl, Q1=CO2H and (HA6)n7=(HCl)2): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring of 4-pyranyl and Q1=CO2H.1H NMR (DMSO-d6, 400 MHz), δ is 1.10 (d, 3H,J=the 6.8 Hz), 1,63-1,71 (m, 2H), 2,03 (d, 2H,J=to 13.6 Hz), 2,82 (s, 3H), of 2.93 (s, 3H), 3,49 (t, 2H,J=10.4 Hz), of 3.77-3,81 (m, 2H), 4,17 (s, 2H), 5,24 is 5.28 (m, 1H), 6,47 (d, 1H), 7,21 (DD, 1H,J=2,4, 8,8 Hz), 7,42 (d, 1H,J=the 2.4 Hz), 7,75-to 7.84 (m, 2H), to $ 7.91 (d, 1H,J=and 8.4 Hz), 8,18 (s, 1H), with 8.33 (s, 1H), 9,94 (s, 1H), 10,38 (s, 1H).

EXAMPLE 5-7a (a compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a cyclohexyl ring, Q1=CO2H and (HA6)n7=(HCl)2): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-and is, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a cyclohexyl ring and Q1=CO2H.1H NMR (CD3OD, 400 MHz) δ of 1.34 (d, 3H,J=of 6.7 Hz), 1,54 was 1.69 (m, 8H), 2,18-of 2.26 (m, 2H), 3,06 (s, 3H), 3,14 (s, 3H), 4,18 (s, 2H), of 5.05-5,14 (m, 1H), of 6.31 (d, 1H), 7,28 (DD, 1H,J=2,3, and 9.1 Hz), 7,34 (s, 1H), 7,69 (d, 1H,J=to 8.7 Hz), 7,76 (s, 1H), 7,89 (d, 1H,J=the 8.9 Hz), of 7.97 (d, 1H,J=8,8 Hz), 8,13 (s, 1H), 8,24 (s, 1H), 9,65 (s, 1H).

EXAMPLE 5-8a (compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, Q1=CO2H and (HA6)n7=(HCl)2): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl and Q1=CO2H.1H NMR (CD3OD, 400 MHz) δ of 1.29 (d, 3H,J=the 6.8 Hz), 1,75 of-1.83 (m, 6H), 2,14-of 2.23 (m, 2H), 3.00 and (s, 3H), of 3.07 (s, 3H), 4,19 (s, 2H), 5,01-5,09 (m, 1H), and 6.25 (d, 1H,J=11.2 Hz), 7,22 (DD, 1H,J=2,4, 8,8 Hz), 7,30 (d, 1H,J=the 2.4 Hz), 7,63 (d, 1H,J=8,8 Hz), of 7.70 (s, 1H), to 7.84 (d, 1H,J=9,2 Hz), to $ 7.91 (d, 1H,J=and 8.4 Hz), 8,07 (d 1H, J=1,6 Hz), 8,18 (d, 1H,J=1.2 Hz), 9,59 (s, 1H).

EXAMPLE 5-9a (a compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)iPr, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl, Q1=CO2H and (HA6)n7=(HCl)2): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)iPr, n2=0, n3=1, R4band R5btaken together with the carbon to which they were attached, form a ring cyclopentyl and Q1=CO2H.1H NMR (CD3OD, 400 MHz) δ 1,12-of 1.16 (m, 3H), 1,31 to 1.76 (m, 8H), of 2.08 (s, 3H), 2,92 are 2.98 (m, 1H), 3,61-to 3.73 (m, 1H), 4.09 to (s, 2H), 6,27 (d, 1H,J=7.5 Hz), 7,12 (DD, 1H,J=2,3, and 9.0 Hz), 7,20 (s, 1H), 7.62mm (s, 2H), of 7.75 (d, 1H,J=9.1 Hz), 7,80-of 7.82 (m, 1H), 8,04 (s, 1H), 8,19 (s, 1H), 9,39 (s, 1H).

EXAMPLE 5-10a (a compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH2CH3)2, n2=0, n3=1, R4band R5b=CH3, Q1=CO2H and (HA6)n7=(HCl)2): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH2CH3)2 , n2=0, n3=1, R4band R5b=CH3and Q1=CO2H.1H NMR (CD3OD, 400 MHz) δ of 1.29 (d, 3H,J=6,8 Hz)to 1.37 (s, 6H), 1,48-and 1.54 (m, 6H), 3.25 to be 3.29 (m, 1H), 3,61-3,66 (m, 1H), of 3.77-3,82 (m, 1H), 4,14 (s, 2H), 5,00-5,04 (m, 1H), 6,47 (d, 1H,J=10.4 Hz), 7,25 (DD, 1H,J=2,8, 9,2 Hz), 7,32 (d, 1H,J=2,4 Hz), 7,72-7,76 (m, 2H), 7,88 (d, 1H,J=9,2 Hz), to 7.93 (d, 1H,J=8,4 Hz), 8,19 (d, 1H,J=1,6 Hz), 8,28-8,29 (m, 1H), 9,67 (s, 1H).

EXAMPLE 5-11a (a compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)-cyclohexyl, n2=0, n3=1, R4band R5b=CH3, Q1=CO2H and (HA6)n7=(HCl)2): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)-cyclohexyl, n2=0, n3=1, R4band R5b=CH3and Q1=CO2H.1H NMR (CD3OD, 400 MHz) δ 1.26-1.28 (in m, 4H), to 1.37 (s, 6H), of 1.45 to 1.47 (m, 3H), of 1.73 to 1.76 (m, 2H), 1,94 is 2.01 (m, 2H), 2,11 and 2.13 (m, 1H), 2,49-to 2.57 (m, 1H), 3,06 (s, 3H), 3.43-3.45 points (m, 1H), 4,13 (s, 2H), 5,08-5,11 (m, 1H), 6,41 (d, 1H,J=11.2 Hz), 7,25 (DD, 1H,J=2,4, 8,8 Hz), 7,31 (d, 1H,J=2,4 Hz), 7,72 to 7.75 (m, 2H), 7,87 (d, 1H,J=9,2 Hz), 7,92 (d, 1H,J=9,2 Hz), to 8.12 (s, 1H), 8,31 (s, 1H), 9,51 (s, 1H).

EXAMPLE 5-12a (a compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)-n-butyl, n2=0, n3=1, R4band R5b=CH3, Q1=CO2H and (HA6)7 =(HCl)2): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)-n-butyl, n2=0, n3=1, R4band R5b=CH3and Q1=CO2H.1H NMR (CD3OD, 400 MHz) δ 1.06 a (t, 3H,J=7,2 Hz), 1,29-of 1.32 (m, 4H), to 1.37 (s, 6H), 1,45-of 1.53 (m, 3H), 1.70 to 1,72 (m, 1H), of 3.07 (s, 3H), 3.04 from-to 3.09 (m, 1H), 3,35-of 3.46 (m, 1H), 4,13 (s, 2H), 6,36 (d, 1H,J=11.2 Hz), 7,25 (DD, 1H,J=2,4, 8,8 Hz), 7,32 (d, 1H,J=2,4 Hz), 7,71-7,73 (m, 2H), 7,87 (d, 1H,J=8,8 Hz), to 7.93 (d, 1H,J=8,4 Hz), 8,16 (s, 1H), 8,28 (s, 1H), 9,60 (s, 1H).

EXAMPLE 5-13a (a compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)iPr, n2=0, n3=1, R4band R5b=CH3, Q1=CO2H and (HA6)n7=(HCl)2): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)iPr, n2=0, n3=1, R4band R5b=CH3and Q1=CO2H.1H NMR (CD3OD, 400 MHz) δ 1.28 (in d, 3H,J=6,4 Hz)to 1.37 (s, 6H)and 1.51 (d, 3H,J=6,8 Hz), was 1.58 (d, 3H,J=6,8 Hz), is 3.08 (s, 3H), 3,76-a 3.83 (m, 1H), 4,14 (s, 2H), 5,02-5,10 (m, 1H), 6.42 per (d, 1H,J=to 10.8 Hz), 7,25 (DD, 1H,J=2,4, 8,8 Hz), 7,31 (d, 1H,J=2,4 Hz), 7,73-to 7.77 (m, 2H), 7,87 (d, 1H,J=8,8 Hz), 7,92 (d, 1H,J=8,8 Hz), 8,18 (s, 1H), 8.34 per (s, 1H), 9,54 (s, 1H).

EXAMPLE 5-14a (the connection is ormula I-HA 6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)Et, n2=0, n3=1, R4band R5b=CH3, Q1=CO2H and (HA6)n7=(HCl)2): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)Et, n2=0, n3=1, R4band R5b=CH3and Q1=CO2H.1H NMR (CD3OD, 400 MHz) δ 1.26 in (d, 3H,J=6,8 Hz)of 1.33 (s, 6H), to 1.48 (t, 3H,J=7,2 Hz), 3,03 (s, 3H), 3,36-to 3.41 (m, 1H), 3,52 is 3.57 (m, 1H), 4,11 (s, 2H), 5,06-5,10 (m, 1H), 6,47 (d, 1H,J=to 10.8 Hz), 7,20 (DD, 1H,J=2,4, 8,8 Hz), 7,27 (s, 1H), 7.68 per-to 7.77 (m, 2H), 7,84-of 7.90 (m, 2H), 8,21-to 8.34 (m, 2H), 9,68 (s, 1H).

EXAMPLE 5-15a (a compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-PhO, n3=1, R4band R5b=H, Q1=CO2H and (HA6)n7=HCO2H): The title compound was obtained by the above described method E with the subsequent application of the method F total synthesis, was used compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-PhO, n3=1, R4band R5b=H and Q1=CO2H, the compound of formula I-B, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-PhO, n3=1, R4band R5b=H, and the connection form of the s I-C, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-PhO, n3=1, R4band R5b=H, and R7=CH3.1H NMR (CD3OD, 200 MHz) δ of 0.93 (d, 3H,J=6,6 Hz), 2,42 (s, 6H), 3,90-to 3.99 (m, 1H), of 4.54 (s, 2H), 5,14 (s, 2H), 5,52 (d, 1H,J=11.2 Hz), 6,97 (d, 2H,J=8,4 Hz), 6.90 to (d, 1H,J=1.4 Hz), 7,25 (DD, 1H,J=2,6 Hz and 6.6 Hz), 7,33-the 7.43 (m, 3H), 7,50-7,58 (m, 2H), 7,81 (d, 2H,J=8,8 Hz), of 7.90-to 7.95 (m, 1H), of 8.37 (s, 1H), 8,44 (s, 1H); MS (ES) 460,0 (M+1).

EXAMPLE 5-16a (compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=0, Q1=CO2H and (HA6)n7=(HCl)2): The title compound was prepared as follows: To the compound 3-27A (100 mg, 0.24 mmol) in THF (500 ml) was added 2M HCl (610 μl, 1,22 mmol) and left to stir at room temperature for 4 hours. The mixture was concentrated in vacuum to obtain compound 5-16A.1H NMR (D2O, 200 MHz) δ of 1.20 (d, 3H,J=6,6 Hz), 2,90 (s, 6H), 4,80 (s, 2H), equal to 6.05 (d, 1H,J=10.0 Hz), 7,17-7,22 (m, 2H), and 7.5 (s, 1H), 7,79-7,83 (m, 2H), 7,94 (d, 2H,J=6,0 Hz), 9,18 (s, 1H); MS (ES) 354,2 (M+1).

EXAMPLE 5-16b (a compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=0, Q1=CO2H and (HA6)n7=(HCl)2): The title compound was obtained in accordance with the procedures described above for compound 5-16A, and the shutting down of the substitution compound 3-27b connection 3-27A. 1H NMR (D2O, 200 MHz) δ 1.32 to (d, 3H,J=7,4 Hz), 2,90 (s, 6H), 4,80 (s, 2H), 7,17-7,22 (m, 2H), and 7.5 (s, 1H), 7,79-7,83 (m, 2H), 7,94 (d, 2H,J=6,0 Hz), 9,18 (s, 1H); MS (ES) 354,3 (M+1).

EXAMPLE 5-17 (a compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=CH3, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, Q1=CO2H and (HA6)n7=(HCl)2): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=CH3, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3and Q1=CO2H. MS (ES) 424,3 (M+1).

Method G General synthesis for the preparation of compounds of the formula I-(HA6)n7(Compound of formula I, in which R1means N, R2=CH3, R3=H, G1=N(CH3)2, n1=1, R4a, R5a, R6aand R6bcorrespond to H, Y means O, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CONR7R8): Acetonitrile solution (0.3 M) of the compounds of formula I (1 EQ.) and 1,1'-carbonyldiimidazole (2 EQ.) boiled under reflux at 80°C for 16 hours. HNR7R8(solution in THF, 1.0 mmol) was added dropwise into the reaction mixture. After stirring for 3 hours, the reaction mixture was concentrated in vacuum, distributed between the saturated NaHCO 3and CH2Cl2and the aqueous layer was extracted with CH2Cl2(5×). The combined organic layers were washed with saturated brine, dried over Na2SO4, filtered and concentrated in vacuum. The obtained residue was purified by HPLC according to Gilson, to obtain the compounds of formula I-(HA6)n7.

EXAMPLE 5-18a (a compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, Q1=CONH2and (HA6)n7=HCO2H): The title compound was obtained by the above method G total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3and Q1=CO2H and HNR7R8=NH3. MS (ES) 395,3 (M+1).

EXAMPLE 5-19a (a compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, Q1=CONHCH3and (HA6)n7=HCO2H): The title compound was obtained by the above method G total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band Rb =CH3and Q1=CO2H and HNR7R8=NH2CH3.1H NMR (CD3OD, 400 MHz) δ of 0.90 (d, 3H,J=6,4 Hz), 1,32 (s, 6H), 2.40 a (s, 6H), is 2.74 (s, 3H), 3,90-3,98 (m, 1H), 4,07 (s, 2H), is 5.06 (d, 1H,J=10.4 Hz), 7,17 (DD, 1H,J=6,4 Hz, 2.4 Hz), 7,24 (d, 1H,J=2,4 Hz), 7,51 (d, 1H,J=8,8 Hz), 7,76-7,81 (m, 3H), 7,89 (s, 1H), 8,39 (s, 1H); MS (ES) 409,2 (M+1).

EXAMPLE 5-20a (a compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, Q1=CON(CH3)2and (HA6)n7=HCO2H): The title compound was obtained by the above method G total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3and Q1=CO2H and HNR7R8=NH(CH3)2. MS (ES) 423,3 (M+1).

Way N General synthesis for the preparation of compounds of the formula I-(HA6)n7(Compound of formula I, in which R1means N, R2=CH3, R3=H, G1=N(CH3)2, n1=1, R4a, R5a, R6aand R6bcorrespond to H, Y means O, n2=0, n3=1, R4band R5b=CH3, n4=1, and Q1=CONR7R8): To a solution of the compounds of formula I (1 EQ.) in DMF, the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (1.5 equiv.) HNR7R8.HCl (1.5 EQ.) 1-hydroxy-isobenzofuranone (0.5 EQ.) was added dropwise diisopropylethylamine (1.5 EQ.) and was stirred for 16 hours. After completion of the reaction, the reaction mixture was concentrated in vacuum, was distributed between saturated NaHCO3and CH2Cl2and the aqueous layer was extracted with CH2Cl2(5×). The combined organic layers were washed with saturated brine, dried over Na2SO4, filtered and concentrated in vacuum. The obtained residue was purified by HPLC according to Gilson, to obtain the compounds of formula I-(HA6)n7.

EXAMPLE 5-21a (a compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-Phenyl, n3=0, Q1=CONH2and (HA6)n7=HCO2H): The title compound was obtained by the above method H total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-Phenyl, n3=0, and Q1=CO2H and HNR7R8=NH3. MS (ES) 429,3 (M+1).

EXAMPLE 5-22a (a compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-Ph, n3=0, Q1=CONHCH3and (HA6)n7=HCO2H): The title compound was obtained by the above method H total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=NCH 3)2, n2=1, Z=4-Phenyl, n3=0, and Q1=CO2H and HNR7R8=NH2CH3. MS (ES) 443,3 (M+1).

EXAMPLE 5-23a (compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-Phenyl, n3=0, Q1=CON(CH3)2and (HA6)n7=HCO2H): The title compound was obtained by the above method H total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-Phenyl, n3=0, and Q1=CO2H and HNR7R8=NH(CH3)2.1H NMR (CD3OD, 400 MHz) δ of 0.91 (d, 3H,J=6,8 Hz)to 2.41 (s, 6H), 2,96 (s, 1H), 3,09 (s, 1H), 3,90-4,10 (m, 1H), 5,26 (s, 2H), of 5.53 (d, 1H,J=to 11.6 Hz), 7,19 (s, 1H), 7,27 (DD, 1H,J=2,4, 6.4 Hz), 7,33 (d, 1H,J=2,8 Hz), 7,37 (d, 1H,J=7,6 Hz), 7,47-rate of 7.54 (m, 4H), 7,60 (d, 1H,J=7,6 Hz), 7,78-of 7.82 (m, 2H), to $ 7.91 (s, 1H), 8,46 (s, 1H); MS (ES) 457,3 (M+1).

EXAMPLE 5-24a (compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH2CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3, Q1=CO2H and (HA6)n7=(HCl)2): The title compound was obtained by the above method F total synthesis, which used the compound of formula I, X1=imidazol-1-yl, R2=CH2CH3, R3=H, G1=N(CH3)2, n2=0, n3=1, R4band R5b=CH3 and Q1=CO2H.1H NMR (CD3OD, 400 MHz) δ 0,81 (t, 3H,J=a 7.6 Hz), of 1.37 (s, 6H), 1,63 is 1.75 (m, 1H), 1.85 to was 1.94 (m, 1H), to 3.02 (s, 3H), 3,10 (s, 3H), 4,11 (s, 2H), 5,06-5,11 (m, 1H), 6,59 (d, 1H,J=the 11.6 Hz), 7,17 (d, 1H,J=2,8 Hz), 7.23 percent (DD, 1H,J=2,4, and 9.2 Hz), 7,42 (s, 1H), 7,47 (s, 1H), 7,74 (DD, 1H,J=2,0, a 8.8 Hz), 7,82-a 7.85 (m, 2H), 8,19 (s, 1H), 8,35 (s, 1H), to 9.91 (s, 1H).

EXAMPLE 5-25a (compound of the formula I-(HA6)n7where X1=imidazol-1-yl, R2=CH3, R3=H, G1=N(CH3)2, n2=1, Z=4-Phenyl, n3=0, Q1=OH and HA6)n7=HCO2H): To a solution of compound 3-6a (20 mg, 0,044 mmol) in methylene chloride (1 ml) was added triperoxonane acid and left to stir at room temperature for 16 hours. After completion of the reaction, the reaction mixture was concentrated in vacuo to solids obtained in a minimal volume of water and neutralized to pH 7 with saturated NaHCO3. White solid, which precipitated from solution, filtered, washed with water and purified by HPLC according to Gilson.1H NMR (CD3OD, 200 MHz) δ of 0.83 (d, 3H,J=6,6 Hz), is 2.30 (s, 6H), 3,70-with 3.79 (m, 1H), 4,32 (s, 2H), 5,32 (d, 1H,J=to 10.6 Hz), 6,63 (d, 2H,J=8,4 Hz), 6.90 to (s, 1H), 7,02 (d, 2H,J=8,8 Hz), 7,21 (d, 1H,J=9,2 Hz), 7,28-7,31 (m, 1H), 7,42 (d, 1H,J=8,4 Hz), to 7.68 (d, 1H,J=9,2 Hz), 7,81-7,89 (m, 2H), 8,58 (s, 2H); MS (ES) 402,0 (M+1).

1. The compound represented by formula I-A

or its pharmaceutically acceptable salt in which
X is selected from imidazolyl and triazolyl;
R2and R3each independently represent H, C1-10-alkyl;
G1means-NR72R82or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, or heterocyclic saturated ring containing N as a heteroatom, and N heteroatom of the heterocyclic saturated ring optionally substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, or heterocyclic saturated ring containing O as heteroatom;
Z means-phenyl-, -phenyloxy-, -CH=CHPh-;
Q1represents a C1-6-alkyl, -OR75, -CO2R75, -CONR75R85, -NO2, -CN;
R4band R5b, each independently, represents H, C1-10-alkyl; or R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10 membered saturated ring or saturated heterocyclic ring containing O as heteroatom;
n2, n3 and n4 each independently represents 0, 1 or 2;
R72, R75, R82and R85, each independently, represents H, C1-10-alkyl, ciclos3-8-alkyl.

2. The connection is giving according to claim 1, in which Q1represents-CO2H or-CO2R75.

3. The connection of claim 1, in which Q1represents a C1-6-alkyl, -CO2R75or-CONR75R85.

4. The compound according to claim 3, in which Q1represents-CO2R75or-CONR75R85.

5. The compound according to claim 3 in which R4band R5beach independently represents H, C1-6-alkyl; or R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10 membered saturated ring.

6. The compound according to claim 5, in which R4bwith R5btaken together with the respective carbon atom to which they attached, form a ring cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

7. The compound according to claim 5, in which R4band R5bboth represent ethyl or both represent methyl.

8. The compound according to claim 3, in which Q1represents-CO2R75.

9. The compound according to claim 3, in which Q1represents-CO2N.

10. The compound according to claim 3, in which G1means di(C1-6-alkyl)amino.

11. The compound according to claim 3, in which G1represents dimethylamino, ethylmethylamino, diethylamino or isopropylethylene.

12. The compound according to claim 3 in which R2and R3, each independently, is predstavljaet a hydrogen, methyl or ethyl.

13. The compound according to claim 3, in which
a) R2means hydrogen; and G1and R3taken together with the carbon atom to which they attach, form

in which • denotes the carbon to which they attach; or
b) R2means hydrogen; and G1and R3taken together with the carbon atom to which they attach, form

in which • denotes the carbon to which they attach.

14. The compound according to claim 1, in which X represents imidazolyl.

15. The compound according to claim 4, in which R2means hydrogen, and R3means methyl.

16. The compound according to claim 4, in which R2means hydrogen, and R3means ethyl.

17. The compound according to claim 4, in which R2and R3both represent methyl.

18. The connection 13, in which n2 is equal to 1, a Z means phenyl.

19. Connection p, where n3 and n4, each equal to 0.

20. The compound according to claim 1, in which Z means-phenyl - or-phenyloxy-.

21. Connection p, where Q1means CO2R75.

22. Connection item 21, in which Q1means CO2H.

23. The compound of formula I-A according to claim 1, which is selected from the group consisting of:
3-[6-(2-dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxy]-2,2-dimethyl-propionic acid;
2-[6-(2-dim is thylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-2-ethyl-butyric acid;
1-[6-(2-dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-cyclopropane-
carboxylic acid;
1-[6-(2-dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-CYCLOBUTANE-
carboxylic acid;
1-[6-(2-dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-cyclopentane-
carboxylic acid;
1-[6-(2-dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-cyclohexane-
carboxylic acid;
1-{6-[1-imidazol-1-yl-2-(isopropylethylene)-propyl]-naphthalene-2-yl-oxymethyl}-
the cyclopentane-carboxylic acid;
3-[6-(2-diethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxy]-2,2-dimethyl-propionic acid;
3-{6-[1-imidazol-1-yl-2-(isopropylethylene)-propyl]-naphthalene-2-yl-oxy}-2,2-dimethyl-propionic acid;
3-{6-[2-ethyl-methyl-amino)-1-imidazol-1-yl-propyl]-naphthalene-2-yl-oxy}-2,2-dimethyl-propionic acid;
3-[6-(2-dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxy]-2,2-dimethyl-propionamide;
3-[6-(2-dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxy]-2,2,N-trimethyl-propionamide;
3-[6-(2-dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxy]-2,2,N,N-tetramethyl-propionamide;
3-[6-(2-dimethylamino-1-imidazol-1-yl-butyl)-naphthalene-2-yl-oxy]-2,2-dimethyl-propionic acid;
4-[6-(2-dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-benzoic acid;
3-[6-(2-dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-about simetal]-benzoic acid;
4-[6-(2-dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-benzamide;
4-[6-(2-dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-N-methyl-benzamide;
4-[6-(2-dimethylamino-1-imidazol-1-yl-propyl)-naphthalene-2-yl-oxymethyl]-N,N-dimethyl-benzamide; and
1-[(6-benzyloxy-naphthalene-2-yl)-(1-methyl-pyrrolidin-2-yl)-methyl]-1H-imidazole.

24. The compound according to claim 1, represented by formula I-A:

or its pharmaceutically acceptable salt, in which

in which X1 denotes imidazol-1-yl, X2 means triazole-1-yl, in which

is an R2R3G1taken together with the carbon (•), to which they attach, and in which the SYN - and anti-configuration are relatively X and G1.

25. The compound represented by formula I-B:

or its pharmaceutically acceptable salt, in which

and where XI means imidazol-1-yl and x2 is a triazole-1-yl, and in which the SYN - and anti-configuration exist concerning X and G.

26. The compound represented by formula II:

or its pharmaceutically acceptable salt, in which

and is R 2R3G1taken together with the carbon (•), to which they attach, and in which the SYN - and anti-configuration are relatively HE and G1.

27. The compound represented by formula III:

or its pharmaceutically acceptable salt, in which

andis an R2R3G1taken together with the carbon (•), to which they attach.

28. The compound represented by formula I-A(HA6)n7:

in which

and And6means HCO2-or CL-;
X1 represents imidazol-1-yl;
n4 is equal to one; and
in which SYN and anti configurations are relative to X and G1.

29. The compound represented by formula II:

or its pharmaceutically acceptable salt, in which
R2and R3each independently represent H, C1-10-alkyl;
G1means-NR72R82or G1and R3taken together with the carbon atom to which they attached, form a 3-10 membered saturated ring, or heterocyclic saturated ring containing N as a heteroatom, and N heteroatom of the heterocyclic saturated ring neo is Astelin substituted by substituent R 72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, or heterocyclic saturated ring containing O as heteroatom;
Z means-phenyl-, -phenyloxy-, -CH=CHPh-;
Q1represents a C1-6-alkyl, -OR75, -CO2R75, -CONR75R85, -NO2, -CN;
R4band R5b, each independently, represents H, C1-10-alkyl; or R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10 membered saturated ring or saturated heterocyclic ring containing O as heteroatom;
n2, n3 and n4 each independently represents 0, 1 or 2;
R72, R75, R82and R85, each independently, represents H, C1-10-alkyl, ciclos3-8-alkyl,
provided that the specified connection is not [2-hydroxy-2-(6-methoxy-2-naphthyl)ethyl]isopropylamino.

30. The compound represented by formula III:

or its pharmaceutically acceptable salt, in which:
R2and R3each independently represent H, C1-10-alkyl;
G1means-NR72R82or G1and R3taken together with the carbon atom to which they attached, form a 3-10-membered saturated the ring or saturated heterocyclic ring, containing N as a heteroatom, and N heteroatom of the heterocyclic saturated ring optionally substituted by substituent R72; or R72and R82taken together with the nitrogen atom to which they attached, form a 3-10 membered saturated ring, or heterocyclic saturated ring containing O as heteroatom;
Z means-phenyl-, -phenyloxy-, -CH=CHPh-;
Q1represents a C1-6-alkyl, -OR75, -CO2R75, -CONR75R85, -NO2, -CN;
R4band R5b, each independently, represents H, C1-10-alkyl; or R4bwith R5btaken together with the respective carbon atom to which they attached, form a 3-10 membered saturated ring or saturated heterocyclic ring containing O as heteroatom;
n2, n3 and n4 each independently represents 0, 1 or 2;
R72, R75, R82and R85, each independently, represents H, C1-10-alkyl, ciclos3-8-alkyl.

31. Pharmaceutical composition having the ability to inhibit the activity of the enzyme cytochrome P450RAI (Sur)containing a therapeutically effective amount of a compound according to claim 1 or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

32. The pharmaceutical composition according p, and pharmaceutical to notice adapted for oral, rectal, local or parenteral administration.

33. The pharmaceutical composition according p, and pharmaceutical composition obtained in the form of tablets, capsules, starch wafers, aerosol, cream, ointment, lotion, powder or suppository.

34. A method of inhibiting the enzyme cytochrome P450RAI (Sur) in a mammal, comprising an introduction to the specified mammal a therapeutically effective amount of a compound according to claim 1 or its pharmaceutically acceptable salt.

35. A method of inhibiting the enzyme cytochrome P450RAI (Sur) in a mammal, comprising an introduction to the specified mammal a therapeutically effective amount of the pharmaceutical composition according p.

36. The compound according to claim 1, characterized by the ratio of the value of the IC50for CYP3A4 activity to the magnitude of the IC50for activity Sur, which is 10:1 or higher.

37. The compound according to claim 1, characterized by the ratio of the value of the IC50for CYP3A4 activity to the magnitude of the IC50for activity Sur, which is 100:1 or higher.



 

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FIELD: organic chemistry, biochemistry, medicine.

SUBSTANCE: invention describes compound of the general formula (3): wherein R15 represents a heterocyclic group chosen from 3-7-membered saturated or 4,7-membered unsaturated monocyclic heterocyclic group comprising 1-4 atoms chosen from nitrogen atom, oxygen atom and sulfur atom, or 7-14-membered polycyclic heterocyclic group comprising 1-4 atoms chosen from nitrogen atom, oxygen atom and sulfur atom that can comprises a substitute; R16 represents a cycloalkyl group comprising 3-7 carbon atoms, monocyclic aromatic hydrocarbon group comprising 6-14 carbon atoms, or heterocyclic group chosen from 3-7-membered saturated or 4-7-membered unsaturated monocyclic heterocyclic group comprising 1-4 atoms chosen from nitrogen atom, oxygen atom and sulfur atom that can comprises a substitute; R17 represents a monocyclic aromatic hydrocarbon group comprising 6-14 carbon atoms or heterocyclic group chosen from 4-7-membered saturated monocyclic heterocyclic group comprising 1-4 atoms chosen from nitrogen atom, oxygen atom and sulfur atom that can comprises a substitute; R18 represents hydrogen atom or (C1-C)-alkyl group; X represents -S-, -SO- or -SO2; or N-oxide or S-oxide of this compound; their salt; or solvate of above described compound. Proposed compounds possess the inhibitory activity against producing/secretion of β-amyloid protein and can be used in treatment of such diseases as Alzheimer's disease, Down's disease and other diseases associated with amyloid deposition.

EFFECT: valuable medicinal properties of inhibitors.

7 cl, 1 tbl, 410 ex

FIELD: organic chemistry, chemical technology, medicine, biochemistry, pharmacy.

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15 cl, 7 tbl, 56 ex

The invention relates to a new method of producing compounds of the formula I

< / BR>
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Antagonist npy y5 // 2264810

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< / BR>
< / BR>
or

< / BR>
< / BR>
< / BR>
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