Pyrimidine derivatives

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel substituted pyrimidine derivatives, possessing properties of inhibiting activity of receptor of kinase insertion domain (KDR), or their pharmaceutically acceptable salts. In formula (1): each of X and Y independently represent O, NR, where R represents H; Z represents CR', where R' represents H or halogen; V, U and T together represent or each of R1, R2, R3, R4 and R6 independently represent H, halogen, cyano, C1-10alkyl; R5 values are given in the invention formula; R7 represents C1-10alkyl.

EFFECT: invention also relates to method of treating angiogenesis-associated disorder such as cancer or age-related macular degeneration.

16 cl, 318 ex

 

Cross-reference to related applications

This application claims the priority of provisional patent application U.S. serial No. 60/911921 filed April 16, 2007. The contents of the earlier application, therefore, is included here by reference in its entirety.

The level of technology

Angiogenesis is a physiological process of growth of new blood vessels from pre-existing vessels. He has a place in a healthy subject in healing wounds, that is, when restoring blood flow in the tissue after surgery or stroke.

Excessive growth of blood vessels may start a specific pathological condition, such as cancer, age-related macular degeneration, rheumatoid arthritis and psoriasis. As a result, new blood vessels are injected into the painful tissue and destroy normal tissue. When cancer new blood vessels also allow tumor cells to enter the bloodstream and deposited in other organs.

Vascular endothelial growth factor (VEGF), homodimeric glycoprotein and its receptor, for example a receptor domain insertions kinase (KDR), are an important way of angiogenesis. Studies have shown that inhibition of KDR leads to apoptosis of endothelial cells and, thus, to the suppression of angiogenesis. See Rubin M. Tuder, Chest, 2000; 117: 281. For this reason, and hibitory KDR are potential candidates for treatment-related angiogenesis diseases.

The invention

The present invention is based on the discovery that a number of pyrimidine compounds inhibits the activity of KDR.

One aspect of the present invention describes pyrimidine compounds of the following formula (I):

(I)

in which each of X and Y independently represents O, S or NR, where R represents H, alkyl, alkenyl, quinil, aryl, cycloalkyl, heteroseksualci, heteroaryl, alkylaryl, alkoxycarbonyl, aminocarbonyl or aminosulfonyl; Z represents CR' or N, where R' represents H, halogen, nitro, cyano, hydroxyl, alkoxy, aryloxy, alkyl, alkenyl, quinil, aryl, cycloalkyl or heteroseksualci; V, U and T together are

or

each of R1, R2, R3, R4and R6independently represents H, halogen, nitro, amino, cyano, hydroxy, alkyl, alkenyl, quinil, aryl, cycloalkyl, heteroseksualci, heteroaryl, alkoxy, alkylthio, alkylsulphonyl, carboxy, alkoxycarbonyl, carbylamine, sulfonylamino, aminocarbonyl or aminosulfonyl; R5represents alkyl, cycloalkyl, heteroseksualci, aryl or heteroaryl and R7represents alkyl.

In relation to formula (I), a is C subgroups of compounds corresponds to the what R1, R2, R3and R4represents H and R5represents aryl or heteroaryl, optionally substituted with halogen, nitro, amino, cyano, hydroxy, alkyl, alkenyl, quinil, aryl, cycloalkyl, heterocyclization, heteroaryl, alkoxy, alkylthio, alkylcarboxylic, carboxy, alkoxycarbonyl, sulfonyl, carbylamine, sulfonylamino, aminocarbonyl or aminosulfonyl. Another sub-group corresponds to the fact that X represents O or NH; Y represents NH; V, U and T together are

thus R6can represent H and R7can represent methyl; or Z represents CR', R' represents H, halogen or alkyl.

The term "alkyl" in the description refers to hydrocarbons with straight or branched chain containing 1-10 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl. The term "alkoxy" refers to-O-alkyl.

The term "aryl" refers to containing 6 carbon atoms, monocyclic containing 10 carbon atoms, bicyclic, contains 14 atoms of carbon tricyclic aromatic ring system, where each ring can have 1-4 substituent. Examples of aryl groups include, but are not exhaust anievas this, phenyl, naphthyl and anthracene.

The term "cycloalkyl" refers to saturated and partially unsaturated cyclic hydrocarbon group having 3-12 carbon atoms. Examples cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl and cyclooctyl.

The term "heteroaryl" refers to an aromatic 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system having one or more heteroatoms (such as O, N or S). Examples of heteroaryl groups include pyridyl, furyl, imidazolyl, benzimidazolyl, pyrimidinyl, thienyl, chinoline, indolyl and thiazolyl. The term "heteroalkyl" refers to an alkyl group, substituted heteroaryl group.

The term "heteroseksualci" refers to a nonaromatic 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system having one or more heteroatoms (such as O, N or S). Examples geterotsiklicheskikh groups include, but are not limited to, piperazinil, pyrrolidinyl, dioxane, morpholinyl and tetrahydropyranyl. Heteroseksualci can be sahariano ring, for example, glucosyl.

Alkyl, cycloalkyl, heteroseksualci, aryl, heteroaryl and alkoxy referred to in the OPI is assured, include both substituted and unsubstituted residues. Examples of substituents include, but are not limited to, halogen, hydroxyl, amino, cyano, nitro, mercapto, alkoxycarbonyl, amido, carboxy, alkanesulfonyl, alkylsulphonyl, urea, carbamyl, carboxyl, touraid, thiocyanato, sulfonamide, alkyl, alkenyl, quinil, alkyloxy, aryl, heteroaryl, cycloalkyl, heteroseksualci, in which alkyl, alkenyl, quinil, alkyloxy, aryl, heteroaryl, cycloalkyl and heteroseksualci may optionally be replaced.

Pyrimidine compounds described above include their pharmaceutically acceptable salts, hydrates and prodrugs, if applicable.

Another aspect of the present invention describes a method of treatment associated with angiogenesis disorders (e.g., cancer or age-related macular degeneration). The method comprises the administration to a subject having such a disorder an effective amount of one or more of the above pyrimidine compounds.

In another aspect, the present invention describes a method of inhibiting the activity of the receptor domain insertions kinase by bringing into contact of the receptor with an effective amount of the pyrimidine compound of the formula (II):

in which R1represents H, alkyl, alkenyl, quinil, aryl, cycloalkyl, g is therotically or heteroaryl; each of R2and R3independently represents H, halogen, nitro, amino, CN, hydroxy, alkyl, alkenyl, quinil, aryl, cycloalkyl, heteroseksualci, heteroaryl, alkoxy, alkylsulphonyl, carboxy or alkoxycarbonyl; each of X and Y independently represents O, S or NR4where R4represents H, alkyl, alkenyl, quinil, aryl, cycloalkyl, heteroseksualci, heteroaryl, alkylaryl, alkoxycarbonyl, aminocarbonyl or aminosulfonyl; and Ar represents an aryl or heteroaryl.

In relation to formula (II), one of the subgroups of compounds corresponds to the fact that Ar represents an indolyl, indazoles, benzoimidazolyl or benzoxazolyl; X represents O or NH and Y represents NH; or R1represents aryl or heteroaryl, optionally substituted with halogen, nitro, amino, cyano, hydroxy, alkyl, alkenyl, quinil, aryl, cycloalkyl, heterocyclization, heteroaryl, alkoxy, alkylthio, alkylcarboxylic, carboxy, alkoxycarbonyl, sulfonyl, carbylamine, sulfonylamino, aminocarbonyl or aminosulfonyl.

Illustrative compounds 1-317 shown below in the section "Detailed description".

Another aspect of the present invention describes a method of inhibiting angiogenesis or treating age-related macular degeneration through the introduction of subje the one in need, an effective amount of the pyrimidine compounds of formula (II)as described above.

Also within the present invention are (1) a composition comprising one or more pyrimidine compounds described above and a pharmaceutically acceptable carrier for use in the treatment associated with angiogenesis disorders (such as cancer or age-related macular degeneration), and (2) applying one or more pyrimidine compounds for obtaining a medicinal product for the treatment of disorders.

Detailed description of one or more embodiments of the present invention are described below in this document. Other characteristics, objectives and advantages of the present invention will be clear from the description and claims.

Detailed description

The compounds described above, can be synthesized from commercially available starting materials using methods well known in the field. For example, you can replace the leaving group (e.g. chloride, p-TsO, MeS or MeSO2on the active N2, N4 positions corresponding pyrimidine compounds nucleophilic groups such as amino or hydroxyl, for example, by reaction of a combination of Buchwald-Hartwig. The substitution may be carried out either in N2 floor the position, or at the N4 position.

The compounds thus obtained may optionally be modified in their peripheral positions with obtaining the desired compounds.

Conversion chemistry synthesis, suitable for use in the synthesis of the desired pyrimidine compounds are described, for example, in R. Larock, Comprehensive Organic Transformations, VCH Publishers (1989); T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 3rdEd., John Wiley and Sons (1999); L. Fieser and M. Fieser, Fieser and Fieser''s Reagents for Organic Synthesis, John Wiley and Sons (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis, John Wiley and Sons (1995) and subsequent editions.

Before using the compounds may be purified by using column chromatography, high performance liquid chromatography, crystallization or other suitable methods.

Pyrimidine compounds described above, when they are in contact with KDR, inhibit the activity of this receptor. An effective amount of one or more of these compounds may for this reason be used for the inhibition of angiogenesis and the treatment of a subject having associated with angiogenesis disorder.

The term "effective amount" refers to the amount of the pyrimidine compound that is required to provide the estimated impact on the subject. Effective amounts may vary, as is obvious to a specialist in this about the Asti, depending on the method of administration used filler and from the possibility of co-usage with other agents. The term "treatment" refers to the introduction of one or more of the preceding pyrimidine compounds to a subject, which is associated with angiogenesis disorder, or has a symptom of such a disorder, or a predisposition to such a disorder, with the purpose to cure, heal, mitigate, relieve, alter, remove, improve, health disorders or affect the disorder, the symptoms of the disorder or the predisposition toward the disorder.

To implement this method, the composition having one or more of the pyrimidine compounds of the present invention may be administered orally, parenterally, by inhalation, by spray, or via an implanted reservoir. The term "parenteral"as used in the description, includes subcutaneous, percutaneous, intravenous, intramuscular, intra-articular, intra-arterial, intrasynovial, intrasternal, intrathecal, vnutrizonovoy and intracranial technology injection or infusion.

The oral composition can be any orally acceptable dosage form including, but not limited to, tablets, capsules, emulsions and odniesienie, dispersions and solutions. Commonly used carriers for tablets include lactose and corn starch. Lubricating agents such as magnesium stearate, are also typically added to the tablets. For oral administration in the form of a capsule, suitable diluents include lactose and dried corn starch. When aqueous suspensions or emulsions are introduced orally, the active ingredient may suspendibility or dissolved in the oil phase, in combination with emulsifying or suspendresume agents. If so desired, can be added to certain sweetening, flavouring or tinted agents.

A sterile composition for injection (for example, aqueous or oily suspension) may be prepared in accordance with technology known in this field, using the appropriate dispersing or wetting agents (such as Tween 80) and suspendida agents. A sterile preparation for injection may also be a sterile solution or suspension for injection in a non-toxic parenterally acceptable diluent or solvent, such, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are mannitol, water, ringer's solution and isotonic chloride hydroxide is I. In addition, sterile, fixed oils are usually used as solvent or suspendida environment (for example, synthetic mono - or diglycerides). Fatty acids such as oleic acid and its glyceride derivatives, are suitable for use in obtaining drugs for injection, insofar as they are natural pharmaceutically-acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylene forms. These oil solutions or suspensions may also contain a diluent or dispersant based on long-chain alcohol or carboxymethyl cellulose or similar dispersing agents.

Composition for inhalation can be obtained in accordance with technology well known in the field of preparation of pharmaceutical preparations, and can be obtained as solutions in saline, using benzyl alcohol or other suitable preservatives, absorption enhancers for increasing the bioavailability, fluorocarbons, and/or other solubilizing or dispersing agents known in this field.

The composition for topical application can be prepared in the form of oil, cream, lotion, ointment and the like. Appropriate carriers for whom is osili include vegetable or mineral oils, white Petroliam (white soft paraffin), fats or oils, branched chain, animal fats and high molecular weight alcohols (greater than C12). Preferred carriers are those in which the active ingredient is soluble. It may also include emulsifiers, stabilizers, moisturizers and antioxidants, and agents, which impart color or fragrance, if desired. In addition to this, these topical preparations can be used substances which promote penetration through the skin. Examples of such enhancers can be found in U.S. patent No. 3989816 and 4444762. Creams are preferably prepared from a mixture of mineral oil, promulging beeswax and water in which the miscible mixture of the active ingredient, dissolved in a small amount of oil, such as almond oil. An example of such a cream is a cream that contains about 40 parts of water, about 20 parts beeswax, about 40 parts of mineral oil and about 1 part almond oil. Ointments can be prepared by mixing a solution of the active ingredient in a vegetable oil, such as almond oil, with warm paraffin and providing a mixture of opportunities for cooling. An example of this ointment is an ointment that contains about 30% wt. mi is yuandong oil and about 70% wt. white soft paraffin.

The carrier in the pharmaceutical composition must be "acceptable" in the sense that it is compatible with the active ingredients of the drug (and preferably, capable of stabilizing it) and is not harmful to the subject, which is treated. For example, solubilizing agents such as cyclodextrins (which form specific, more soluble complexes with one or more active pyrimidine compounds of the extract), can be used as pharmaceutical carriers for delivery of active ingredients. Examples of other carriers include colloidal silicon dioxide, magnesium stearate, cellulose, nutriceuticals and D&C Yellow #10.

Appropriate in vitro can be used for a preliminary assessment of the effectiveness of the above pyrimidine compounds in the inhibition of the activity of KDR or inhibition of VEGF activity. The compounds can further be examined for their effectiveness in the treatment associated with angiogenesis disorders by analyzing in vivo. For example, the compounds can be administered to an animal (e.g., mice)that have cancer, and their therapeutic effects are then estimated. On the basis of these results can also determine an appropriate range of doses and method of administration.

Without additional ut is Chania, it is assumed that the above description gives an adequate opportunity to implement the present invention. The following specific examples, for this reason, should be considered only as illustrative and not restrictive, the rest of the description in any way.

Example 1: Synthesis of N4-(2-methyl-1H-indol-5-yl)-N2-phenylpyrimidine-2,4-diamine (compound 1)

Et3N (1 mmol) are added to a solution of 2,4-dichloropyrimidine (1 mmol) and 5-amino-2-methylindole (1 mmol) in 5 ml EtOH. The reaction mixture is heated under reflux for 5 hours. After removal of the solvent in vacuo and addition of H2O, the mixture is extracted with EtOAc. The organic layers are combined, washed with saturated NaCl solution, dried over anhydrous Na2SO4and concentrated in vacuo. The resulting residue is purified by column chromatography to obtain N-(2-chloropyrimidine-4-yl)-2-methyl-1H-indol-5-amine to yield 80%.

N-(2-chloropyrimidine-4-yl)-2-methyl-1H-indol-5-amine (0.1 mmol) and aniline (0.1 mmol) dissolved in 0.5 ml of DMF. Added p-TsOH monohydrate (0.2 mmol). The reaction mixture was stirred at 60°C for 5 hours, diluted with water and extracted with ethyl acetate. The organic layer is successively washed with water and saturated salt solution, dried over anhydrous Na2SO4and the end of tryout. The resulting residue is purified by column chromatography to obtain specified in the header of product with a yield of 85%.

1H NMR (CD3OD 400 MHz): δ 7,831 (d, J=6.0 Hz, 1H), 7,633 (t, J=8.0 to about 7.6 Hz, 3H), UAH 7,262 (t, J=8,4 and 7.6 Hz, 3H), 7,064 (d, J=6,8 Hz, 1H), 6,995 ((t, J=7,6 to 7.2 Hz, 1H), 6,133 (t, J=6.4 to 2.0 Hz, 2H), 2,439 (s, 3H); MS (m/e): 384,2 (M+1).

Examples 2-283: Synthesis of compounds 2-283

Connection 2-283, each synthesized in a manner similar to that described in example 1.

ConnectionName/structure1H NMR (400 MHz, δ ppm)/MS
2N2-(3-ethynylphenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 7,848 (d, J=6,8 Hz, 1H), 7,730 (s, 1H), 7,704 (d, J=8.0 Hz, 1H), 7,507 (s, 1H), 7,275 (d, J=8.0 Hz, 1H), 7,200 (t, J=8.0 Hz, 1H), 7,093-7,036 (m, 2H), 6,639 (m, 2H), 2,425 (s, 3H); MS (m/e): 340,4 (M+1)
3N2-(3-bromophenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 7,879 (s, 1H, 7,784 (J=6.0 Hz, 1H), 7,437 (user., 1H), 7,373 (s, 1H), 7,255 (d, J=8,8 Hz, 1H), 7,079 (user., 2H), 6,968 (d, J=8,4 Hz, 1H), 6,133 (s, 1H), 6,041 (d, J=6,4 Hz, 1H), 2,400 (s, 3H); MS (m/e): 394,3 (M)
4N2-(3-forfinal)-N4-(2-methyl-1H-ind the l-5-yl)pyrimidine-2,4-diamine
(CD3OD): 7,923 (s, 1H), 7,759 (d, J=6.0 Hz, 1H), 7,641 (d, J=8.0 Hz, 1H), 7,397 (s, 1H), 7,247 (d, J=8,4 Hz, 1H), 7,179-at 7,053 (m, 1H), 6,963 (d, J=8,4 Hz, 1H), 6,575 (t, J=8.0 Hz, 1H), 6,125 (s, 1H), 6,044 (d, J=6,0 Hz, 1H), 2,395 (s, 3H); MS (m/e): 334,2 (M+1)

5N2-(3-chlorophenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 7,838 (d, J=6,8 Hz, 1H), 7,746 (s, 1H), 7,526 (user., 2H), 7,298 (d, J=8,4 Hz, 1H), 7,212 (t, J=8.0 Hz, 1H), 7,102 (d, J=8,4 Hz, 1H), 7,001 (d, J=8.0 Hz, 1H), 6,217 (d, J=6.0 Hz, 1H), 6,133 (s, 1H), 2,436 (s, 3H); MS (m/e): 350,2 (M+1)
6N4-(2-methyl-1H-indol-5-yl)-N2-(3-(trifluoromethyl)phenyl) pyrimidine-2,4-diamine
(CD3OD): 8,045 (d, J=7.2 Hz, 1H), 7,788 (d, J=6.0 Hz, 2H), 7,529 (s, 1H), 7,366 (d, J=6,8 Hz, 1H), 7,276 (d, J=8,4 Hz, 1H), 7,228 (d, J=7.2 Hz, 1H), 7,083 (d, J=1.2 Hz, 1H), 6,190 ((d, J=6,4 Hz, 1H), 6,115 (s, 1H), 2,440 (s, 3H), MS (m/e): 384,2 (M+1)
7N4-(2-methyl-1H-indol-5-yl)-N2-(3-
(methylsulphonyl)phenyl)
pyrimidine-2,4-diamine
(CD3OD): 11,471 (s, 1H), 9,461 (s, 1H), 9,364 (s, 1H), 8,441 (s, 1H), 8,236 (s, 1H), 7,988 (d, J=5.6 Hz, 1H), 7,396 (M, 5H), 7,303 (d, J=8,4 Hz, 1H), 6,255 (d, J=5.6 Hz, 1H), 3,111 (s, 3H), 2,456 (s, 3H), MS (m/e): 393,2 (M+1)

8N2-(3-methoxyphenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 8,050 (s, 1H), 7,943 (d, J=6.0 Hz, 1H), 7,440-7,362 (m, 3H), 7,293 (s, 1H), 7,223 (t, J=8.0 Hz, 2H), 7,122 (d, J=7,6 Hz, 1H), 7,0211 (d, J=6,8 Hz, 1H), 6,808 (s, 1H), 6,680 (d, J=6,4 Hz, 1H), 6,222 (s, 1H), 6,068 (d, J=5.6 Hz, 1H), 3,790 (s, 3H), 2,472 (s, 3H); MS (m/e): 345,9 (M+1)
9ethyl 1-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)
benzyl)piperidine-4-carboxylate
(CD3OD): 8,019 (s, 1H), 7,889 (d, J=5.6 Hz, 1H), 7,554 (s, 1H), 7,399 (d, J=8.0 Hz, 1H), KZT 7,328 (d, J=8,4 Hz, 1H), 7,278 (t, J=8.0 Hz, 1H), 7,101 (d, J=8.0 Hz, 1H), 7,002 (d, J=7.2 Hz, 1H), 6,180 (d, J=6.0 Hz, 1H), 6,141 (s, 1H), 4,166 (sq, J=7.2 Hz, 1H), 3,586 (s, 2H), 2,973-2,943 (m, 2H), 2,462 (s, 3H), 2,316 (user., 1H), 2,089 (m, 2H), 1,939-1,885 (m, 2H), 1,741-1,653 (m, 2H), 1,272 (t, J=7.2 Hz, 2H); MS (m/e): 485,4 (M+1)
10N2,N4-bis(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 7,675 (d, J=6,4 Hz, 1H), 7,625 (s, 1H), 7,577 (user., 1H), 7,266-7,219 (m, 2H), 7,068-7,051 (m, 1H), 6,116 (d, J=6.0 Hz, 1H), 6,072 (s, 1H), 6,014 (s, 1H), 2,435 (s, 3H), 2,425 (s, 3H); MS (m/e): 369,3 (M+1)

11N2-(1H-indazol-5-yl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 12,385 (s, 1H), 10,928 (s, 1H), 9,120 (s, 1H), 9,003 (s, 1H), 8,259 (s, 1H), of 7.920 (d, J=6.0 Hz, 1H), 7,758 (s, 1H), 7,667 (s, 1H), 7,541 (d, J=8,8 Hz, 2H), 7,399 (d, J=8,8 Hz, 1H), 7,242 (d, J=8,8 Hz, 1H), 7,15l (d, J=8,8 Hz,1H), 6,142 (d, J=6.0 Hz, 1H), 6,017 (s, 1H), 2,389 (s, 3H), MS (m/e): 356,3 (M+1)
12N2-(1H-benzo[d]imidazol-5-yl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 10,853 (s, 1H), 9,033 (s, 1H), 8,956 (s, 1H), 8,077 (user., 2H), 7,925 (d, J=6.0 Hz, 1H), 7,736 (s, 1H), 7,533 (d, J=8.0 Hz, 1H), 7,444 (d, J=8,8 Hz, 1H), 7,214-7,144 (m, 2H), 6,131 (d, J=6.0 Hz, 1H), 6,020 (s, 1H), 2,372 (s, 3H); MS (m/e): 356,3 (M+1)
13N2-(2-methoxyphenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 8,496 (s, 1H), 8,002 (d, J=6.0 Hz, 2H), 7,446 (s, 1H), 7,047 (DD, J=8,8 Hz, J=2.4 Hz, 1H), 6,981-6,957 (m, 2H), 6,913-6,771 (m, 1H), 6,889 (s, 1H), 6,243 (s, 1H), 6,083 (d, J=6.0 Hz, 1H), 3,910 (s, 3H), 2,490 (, 3H), MS (m/e): 346,2 (M+1)

14N2-(2-chlorophenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 8,385 (d, J=6.0 Hz, 1H), 7,914 (s, 1H), 7,849 (s, 1H), 7,325 (d, J=7,6 Hz, 1H), 7,237 (d, J=8,4 Hz, 1H), 7,182 (t, J=7,6 Hz, 1H), 6,945-6,870 (m, 2H), 6,119 (s, 1H), 6,070 (d, J=6.0 Hz, 1H), 2,397 (s, 3H); MS (m/e): 350,1 (M+1)
15 N2-(2-bromophenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 10,860 (s, 1H), 9,204 (s, 1H), 8,140 (d, J=8,4 Hz, 1H), 7,916 (d, J=5.6 Hz, 2H), 7,651 (d, J=7,6 Hz, 2H), 7,334 (t, J=7,6 Hz, 1H), 7,184 (d, J=8,8 Hz, 1H), 7,038 (user., 2H), 6,192 (d, J=6.0 Hz, 1H), 6,012 (s, 1H), 2,369 (s, 3H); MS (m/e): 394,3 (M)
16N2-(4-forfinal)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 10,889 (s, 1H), 9,256 (s, 1H), 9,245 (s, 1H), 7,966 (d, J=5.6 Hz, 1H), 7,752 (m, J=8.4 and 3.6 Hz, 2H), 7,236 (d, J=5.4 Hz, 1H), 7,133 (m, J=8.4 and 3.6 Hz, 3H), 6,086 (d, J=5.6 Hz, 1H), 6,050 (s, 1H), 2,402 (s, 3H); MS (m/e): 334,2 (M+1)

17methyl 2-(4-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)acetate
(CD3OD): 10,907 (s, 1H), 9,132 (s, 1H), 9,015 (s, 1H), 7,914 (s, 1H), 7,713 (d, J=6 Hz, 1H), 7,498 (d, J=6,8 Hz, 1H), 7,217 (d, J=7.2 Hz, 1H), 7,127 (m, 4H), 6,149 (d, (d, J=6 Hz, 1H), 6,067 (s, 1H), 2,384 (s, 3H), 2,272 (s, 3H), 1,288 (s, 2H), MS (m/e): 387,2 (M+1)
18N4-(2-methyl-1H-indol-5-yl)-N2-(4-phenoxyphenyl)pyrimidine-2,4-diamine
(CD3OD): 10,855 (s, 1H), 9,098 (s, 1H), 9,065 (s, 1H), 7,909 (d, J=5.6 Hz, 1H), 7,786 (d, J=8 Hz, 2H), 7,365 (t, J=7,6 Hz, 2H), 7,346 (s, 1H), 7,201 (d, J=8,8 Hz, 1H), 7,086 (m, 2H), 6,962 (d, 8 Hz, 2H), 6,895 (d, J=8 is t,2H), 6,137 (d, J=5.6 Hz, 1H), 6,021 (s, 1H), 2,33l (s, 3H), MS (m/e): of 407.5 (M+1)
19N2-(4-methoxyphenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 11,097 (s, 1H), 9,479 (s, 1H), 9,243 (s, 1H), 8,090 (d, J=6 Hz, 1H), 7,923 (s, 1H), 7,822 (m, 2H), 7,420 (l, 8,8 Hz, 1H), 7,307 (s, 1H), 7,025 (d, J=8,8 Hz, 2H), 6,340 (m, 1H), 6,265 (s, 1H), 3,941 (s, 3H), 2,591 (s, 3H); MS (m/e): 345,4 (M+1)

20N4-(2-methyl-1H-indol-5-yl)-N2-(4-(2-morpholinoethoxy)phenyl)
pyrimidine-2,4-diamine
(CD3OD): 10,899 (s, 1H), 9,074 (s, 1H), 8,823 (s, 1H), 7,869 (d, J=6 Hz, 1H), 7,713 (s, 1H), 7,621 (d, J=8,8 Hz, 2H), 7,200 (d, J=8,4 Hz, 1H), 7,080 (s, 1H), 6,784 (m, 2H), 6,101 (d, J=5.6 Hz, 1H), 6,025 (c? 1H), 4,034 (t, J=5.6 Hz, 2H), 3,585 (t, J=4.8 Hz, 4H), 2,679 (t, J=5.6 Hz, 2H), 2,475 (t, J=6,4 Hz, 4H), 2,375 (s, 3H); MS: 444,5 (M+1)
21N2-(3,4-differenl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 11,234 (c, 1H), 9,886 (s, 1H), 9,754 (s, 1H), 7,966 (d, J=5.6 Hz, 2H), 7,752 (s, 1H), 7,393 (m, J=8.4 and 3.6 Hz, 3H), 7,133 (d, J=5.6 Hz, 1H), 6,251 (d, J=4.5 Hz, 1H), to 6.19 (s, 1H), 2,402 (s, 3H); MS (m/e): 352,2 (M+1)
22N2-(3, 5dimethylphenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 10,863 (s, 1H), 9,051 (s, 1H), 8,841 (s, 1H), 7,905 (d, J=6 Hz, 1H), 7,633 (s, 1H), 7,361 (s, 1H), 7,207 (m, 2H), 6,507 (s, 1H), 6,118 (d, J=5.6 Hz, 1H), 6,032 (s, 2H), at 2,370 (s, 3H), 2,171 (s, 6H); MS (m/e): 343,4 (M+1)
232-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)ethanol
(CD3OD): 7,939 (d, J=8.0 Hz, 1H), 6,923 (d, J=6,8 Hz, 2H), 6,437 (s, 1H), 6,328 (d, J=7,6 Hz, 2H), 6,218 (s, 1H), 6,231 (d, J=5.6 Hz, 1H), 5,726 (d, J=7.2 Hz, 1H), 3,735 (t, J=7,2 is 6.4 Hz, 3H), 3,225 (t, J=6,8-5,6 Hz, 3H), 2,247 (s, 3H); MS (m/e): 384,1 (M+1)

24N4-(2-methyl-1H-indol-5-yl)-N2-(2-morpholinoethyl)pyrimidine-2,4-diamine
(CD3OD): 7,796 (d, J=6.0 Hz, 1H), 7,497 (s, 1H), 7,246 (d, J=8,8 Hz, 1H), 7,076 (d, J=2,8 Hz, 1H), 6,148 (s, 1H), 5,625 (d, J=4,8 Hz, 1H), 3,760 (m, J=3,2-2,8 Hz, 4H), 3,165 (t, J=3,2-2,4, 2H), 2,619 (t, J=2.0 to 08 Hz, 2H), 2,447 (m, J=2.0 to 1.2 Hz, 4H), 2,317 (s, 3H), MS (m/e): 353,2 (M+1)
25N-cyclopropyl-2-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-
ylamino)phenyl)ndimethylacetamide
(DMSO-d6,): of 7.920 (d, J=5.6 Hz, 1H), 7,700 (m, 2H), 7,546 (s, 1H), 7,220 (d, J=8.0 Hz, 1H), 7,120 (m, 2H), 6,778 (d, J=8.0 Hz, 1H), 6,200 (d, J=6.0 Hz, 1H), 6,066 (s, 1H), 3,027 (s, 2H ), 2,593 (m, 1H), 2,380 (s, 3H), 0,608 (m, 2H), 0,404 (m, 2H), MS (m/e): 413,5 (M+1)
26N2-(3-(2-(who metilamino)
ethylsulfonyl)phenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 8,237 (s, 1H), 8,042 (d, J=6,8 Hz, 1H), 7,867 (d, J=6.0 Hz, 1H), 7,477 (s, 1H), 7,465 (user., 2H), 7,253 (d, J=8,8 Hz, 1H), 7,028 (d, J=8.0 Hz, 1H), 6,141 (d, J=5.6 Hz, 1H), 6,088 (s, 1H), 3,230 (t, J=7,6 Hz, 2H), 2,666 (t, J=7.2 Hz, 2H), 2,409 (s, 3H), 2,165 (s, 6H); MS: 451,4 (M+1)

27N4-(2-methyl-1H-indol-5-yl)-N2-(3-(1-
(methylsulphonyl)
piperidine-4-yloxy)phenyl)pyrimidine-2,4-diamine
(DMSO-d6): 10,976 (s, 1H), at 9,240 sq (s, 1H), 9,036 (s, 1H), 7,054-8,014 (m, 7H), 6,401-6,564 (m, 1H), 6,114-6,278 (m, 1H), 6,012-6,073 (m, 1H), 4,224-4,383 (m, 1H), 3,110-to 3.209 (m, 2H), 2,770-2,886 (m, 2H), at 2,370 (s, 3H), 1,806-1,970 (m, 2H,), 1,578-1,712 (m, 1H); MS (m/e): 493,5 (M+1)
28N-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)
methanesulfonamide
(CD3OD): 7,856 (d, J=6.0 Hz, 1H), 7,652 (s, 1H), 7,543 (s, 1H), 7,432 (DD, J=8,4 Hz, 1H), 7,271 (d, J=8,4 Hz, 1H), 7,196 (t, J=8.0 Hz, 1H), 6,882 (DD, J=8.0 Hz, 2H), 6,130 (d, J=6.0 Hz, 2H), 2,440 (s, 3H), 2,172 (s, 3H); MS (m/e): 409,3 (M+1)
29N4-(2-methyl-1H-indol-5-
yl)-N2-(3-(2-morpholinoethoxy)phenyl)
pyrimidine-2,4-diamine
(DMSO-d6): δ 10,825 (s, 1H), 9,023 (s, 1H),8,986 (s, 1H), 7,927 (d, J=5.6 Hz, 1H), 7,703 (s, 1H), 7,429 (s, 1H), 7,351 (d, J=2.4 Hz, 1H), 7,208 (d, J=8,8 Hz, 1H), 7,076 (m, J=8 Hz, 2H), 6,469 (DD, J=8, 2.4 Hz, 1H), 6,118 (d, J=2 Hz, 1H), 6,057 (s, 1H), 3,933 (t, J=5.6 Hz, 2H), 3,551 (t, J=4.8 Hz, 4H), 2,591 (t, J=5.6 Hz, 2H), 2,40l (t, J=4.8 Hz, 4H), 2,379 (s, 3H); MS (m/e): 444,5 (M+1)

30N2-(3-(3-(dimethylamino) propoxy)phenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 10,836 (s, 1H), 9,021 (s, 1H), 8,983 (s, 1H), 7,926 (d, J=6 Hz, 1H), 7,691 (s, 1H), 7,419 (s, 1H), 7,345 (d, J=8,4 Hz, 1H), 7,212 (d, J=8,4 Hz, 1H), 7,079 (m, 2H), 6,444 (DD, J=8, 2.4 Hz, 1H), 6,118 (d, J=6 Hz, 1H), 6,062 (s, 1H), 3,835 (t, J=6 Hz, 2H), 2,317 (s, 3H), 2,318 (t, J=7.2 Hz, 2H), 2,154 (s, 6H), to 1.767 (t, J=7.2 Hz, 2H); MS (m/e): 416,5 (M+1)
312-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethanol
(CD3OD): 10,902 (s, 1H), 9,087 (s, 1H), 8,986 (s, 1H), of 7.917 (d, J=4 Hz, 1H), 7,683 (s, 1H), 7,405 (m, 2H), 7,227 (m, 1H), 7,104 (m, 1H), 6,458 (d, J=8 Hz, 1H), 6,141 (s, 1H), 6,050 (m, 2H), 5,594 (m, 1H), 3,873 (t, J=5.6 Hz, 2H), 3,653 (t, J=6 Hz, 2H), 2,376 (s, 3H); MS (m/e): 375,4 (M+1)

322-(2-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethanol
(CD3OD): 10,851 (s, 1H), 9,117 (s, 1H), 8,431 (d, J=8.0 Hz, 1H), ,938 (d, J=6.0 Hz, 1H), 7,869 (s, 1H), 7,689 (user., 1H), 7,228 (d, J=8,8 Hz, 1H), 6,983-at 7,053 (m, 2H), 6,836-6,923 (m, 2H), 6,147 (d, J=6.0 Hz, 1H), 6,079 (s, 1H), 5,137 (t, J=5.6 Hz, 1H), 4,061 (sq, J=11.2 Hz, 1.2 Hz, 2H), 3,767 (sq, J=9.6 Hz, 5.6 Hz, 2H), 2,389 (s, 3H); MS (m/e): 376.3 on (M+1)
33N4-(2-methyl-1H-indol-5-yl)-N2-(2-(2-morpholinoethoxy)phenyl) pyrimidine-2,4-diamine
(CD3OD): 10,845 (s, 1H), 9,112 (s, 1H), 8,377 (d, J=7,6 Hz, 1H), 7,935 (d, J=6.0 Hz, 1H), 7,823 (s, 1H), 7,647 (user., 1H), 7,219 (d, J=8,8 Hz, 1H), 7,061 (d, J=8 Hz, 2H), 6,889-6,950 (m, 2H), 6,147 (d, J=6.0 Hz, 1H), 6,074 (s, 1H), 4,182 (t, J=6.0 Hz, 2H), 3,592 (t, J=4.8 Hz, 4H), 2,692 (t, J=5,2 Hz, 2H), 2,471 (user., 4H), 2,388 (s, 3H); MS (m/e): 445,3 (M+1)
34N-methyl-3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzamide
(DMSO-d6): δ 11,015 (s, 1H), 10,776 (s, 1H), 10,593 (s, 1H), 8,493 (d, J=4 Hz, 1H), 7,938 (m, 2H), 7,803 (d, J=2 Hz, 1H), 7,651 (m, 2H), 7,374 (m, 1H), 7,210 (m, 2H), 6,467 (m, 1H), 6,046 (s, 1H), 2,779 (d, 4.4 Hz, 3H), 2,379 (s, 3H); MS (m/e): 373,4 (M+1)

353-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-
(piperidine-1-yl)ethyl)benzamide
(CD3OD): 10,832 (s, 1H), 9,156 (s, 1H), 9,056 (s, 1H), 8,157 (s, 1H), 8,054 (s, 1H), 7,946 (m, 2H), 7,700 (user., 1H), 7,319 (m, 2H), 7,199 (m, 2H), 6,159 (s, 1H), 6,052 (s, 1H), 3,180 (t, J=5.6 Hz, 2H), of 2.38 (s, 3H), 1,480 (s, 6H), 1,372 (s, 4H), 1,229 (s, 2H), MS (m/e): 469,6 (M+1)
36N-(2-(dimethylamino)ethyl)-3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzamide
(CD3OD): 10,846 (s, 1H), 9,149 (s, 1H), 9,077 (s, 1H), 8,181 (t, J=5.6 Hz, 1H), 8,036 (m, 2H), 7,934 (m, 1H), 7,706 (user., 1H), 7,340 (m, 1H), 7,270 (m, 1H), 7,203 (m, 1H), 7,137 (m, 1H), 6,160 (d, J=5.6 Hz, 1H), 6,054 (s, 1H), 3,313 (t, J=6.4 Hz, 2H), 3,175 (t, J=5.6 Hz, 2H), 2,376 (s, 3H), 2,175 (s, 6H), MS (m/e): of 429.5 (M+1)

(CD3OD): 8,198 (d, J=6,4 Hz, 1H), 7,974 (s, 1H), 7,363-7,283 (m, 2H), 6,935 (m, 2H), 6,742 (t, J=8,4 Hz, 1H), 6,260 (s, 1H), 6,200 (d, J=5.6 Hz, 1H), 3,771 (s, 3H), 2,493 (s, 3H), MS (m/e): 347,2 (M+1)
37N2-(3-(4-methoxyphenyl)-1H-pyrazole-5-yl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(DMSO-d6): δ 12,354 (s, 1H), 10,911 (s, 1H), 8,985 (user., 2H), 7,901 (s, 1H), 7,599 (user., 2H), 7,259 (d, J=8,4 Hz, 1H), 7,037 (s, 1H), 6,941-6,913 (m, 2H), 6,099 (user., 2H), 3,787 (s, 3H), 2,493 (s, 3H); MS (m/e): 412,8 (M+1)
38N-(3-ethynylphenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine
(CD3OD): 8,190 (d, J=6.0 Hz, 1H), 8,098 (s, 1H), 7,612 (s, 1H), 7,489 (d, J=8.0 Hz, 1H), 7,339-7,284 (m, 2H), at 7,053 (t, J=8,4 Hz, 1H), 6,937 (DD, J=8,4 Hz, 2.0 Hz, 2H), 6,294 (d, J=6.0 Hz, 2H), 6,262 (s, 1H), 2,495 (s, 3H); MS (m/e): 341,1 (M+1)
39N-(4-methoxyphenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine
414-(2-methyl-1H-indol-5-yloxy)-N-(4-phenoxyphenyl)pyrimidine-2-amine
(CD3OD): 8,201 (d, J=5.6 Hz, 1H), 7,373 (m, J=8,8-5,2 Hz, 4H), 7,188 (d, J=2.0 Hz, 1H), 7,081 (t, J=7,2-6,8 Hz, 1H), 6,989 (d, J=3.2 Hz, 2H), 6,890 (d, J=8,4 Hz, J=2.0 Hz, 1H), 6,644 (d, J=9,2 Hz, 2H), 6,323 (d, J=6,4 Hz, 1H), 6,137 (s, 1H), 2,376 (s, 3H), MS (m/e): 409,3 (M+1)

42N-(3-methoxyphenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine
(CD3OD): 8,236 (d, J=5,2 Hz, 1H), 7,983 (s, 1H), 7,314-7,283 (m, 2H), 7,239 (user., 1H), 7,063 (t, J=8.0 Hz, 1H), 6,981 (d, J=8.0 Hz, 1H), 6,981 (DD, J=8,8 Hz, 2.0 Hz, 1H), 6,528 (d, J=8.0 Hz, 1H), 6,278-6,253 (m, 1H), 3,571 (s, 1H), 2,493 (s, 3H), MS (m/e): 347,2 (M+1)
434-(2-methyl-1H-indol-5-yloxy)-N-(3-(3-(thiomorpholine-1',1'-dioxide)propoxy)phenyl)
pyrimidine-2-amine
CD3OD): 8,298 (s, 1H), 7,996 (d, J=5.6 Hz, 1H), 7,385 (d, J=8,4 Hz, 1H), 7,197 (t, J=8.0 Hz, 1H), 7,094 (d, J=8,4 Hz, 2H), 6,791 (s, 1H), 6,543 (d, J=8.0 Hz, 1H), 6,333 (s, 1H), 5,995 (d, J=6.0 Hz, 1H), 5,321 (s, 1H), 3,974 (t, J=5.6 Hz, 1H), 3,077 (m, 8H), 2,699 (t, J=6,8 Hz, 1H), 2,468 (s, 3H), 1,926 were (t, J=6,8 Hz, 2H);
N-methyl-3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzamide
(DMSO-d6): 11,130 (s, 1H), 9,631 (s, 1H), 8,324 (d, J=4,2 Hz, 1H), 8,309 (s, 1H), 7,994 (s, 1H), 7,741 (s, 1H), 7,308 (d, J=9,2 Hz, 1H), 7,219 (d, J=1.6 Hz, 1H), 7,052 (t, J=2.0 to 0.8 Hz, 2H), 6,932 (m, 1H), 6,272 (d, J=3.6 Hz, 1H), 6,140 (d, J=4,2 Hz, 1H), 5,249 (s, 1H), 2,801 (s, 3H), 2,437 (s, 3H), 2,401 (m, 2H); MS (m/e): 374,3 (M+1)

45trifter-N-(4-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)
methanesulfonamide
(DMSO-d6): 11,248 (s, 1H), 9,304 (s, 1H), 9,153 (s, 1H), 7,960 (s, 1H), 7,913 (d, J=6.0 Hz, 1H), 7,543 (d, J=4.4 Hz, 2H), 7,132 (d, J=8,4 Hz, 1H), 7,063 (m, 1H), 6,910 (t, J=3,6 Hz, 2H), 6,217 (s, 1H), 6,106 (t, J=1.6 to the 2.4 Hz, 1H), 2,411 (s, 3H) MS (m/e): 464,4 (M+1)
46(S)-4-(2-methyl-1H-indol-5-yloxy)-N-(3-(pyrrolidin-3-yloxy)phenyl)pyrimidine-2-amine
(DMSO-d6): 11,122 (s, 1H), 9,515 (s, 1H), UAH 8.306 (d, J=5.6 Hz, 1H), 7,156-7,332 (m, 4H), 6,951 (t, J=8.0 Hz, 1H), 6,827 (DD, J=8,4 Hz, 2.0 Hz, 1H), 6,427 (DD, J=8,4 Hz, 2.0 Hz, 1H), 6,267 (d, J=6.0 Hz, 1H), 6,139 (s, 1H), 6,639 (m, 2H), 4,652-4,711 (m, 1H), 2,964-3,154 (m, 4H), 2,401 (s, 3H), 1,958-1,993 (m, 1H), 1,825-1,898 (m, 1H); MS (m/e): 402,4 (M+1)
47N-methyl-3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)
Benzols honami
(CDCl3): 8,290 (d, 1H), 8,115 (s, 1H), 7,994 (s, 1H), 7,504 (d, J=8, 1H), 7,409 (m, 2H), 7,247 (d, J=8, 1H), 6,958 (m, J=10,8), 6,403 (d, J=5,6, 1H), 6,254 (s, 1H), 2,505 (s, 3H), 2,478 (d, J=5,6, 3H), MS (m/e): 410,1 (M+1)

48N-(4-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)
methanesulfonamide
(CD3OD): 11,204 (s, 1H), 9,120 (s, 1H), 8,837 (s, 1H), 7,959 (d, J=5.6 Hz, 1H), 7,791 (d, J=6,8 Hz, 2H), 7,144 (s, 1H), 7,026 (d, J=7,6 Hz, 2H), 6,922 (d, J=7.2 Hz, 1H), 6,210 (s, 1H), 6,115 (s, 1H), 4,007 (s, 3H), 2,405 (s, 3H); MS (m/e): 358,2 (M+1)
492-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)-N-(2-morpholinoethyl)ndimethylacetamide
(CD3OD): 11,211 (s, 1H), 8,935 (s, 1H), 8,760 (s, 1H), 7,959 (t, J=8,8 and 5.6 Hz, 2H), 7,376 (s, 1H), 7,276 (d, J=7,6 Hz, 1H), 7,120 (t, J=8,8 and 4.4 Hz, 1H), 6,896 (t, J=8.0 Hz, 2H), 6,403 (t, J=2.0 to 1.6 Hz, 1H), 6,205 (, 1H), 6,004 (s, 1H), 3,560 (s, 3H), 2,405 (s, 3H); MS (m/e): 364,2 (M+1)
504-(2-methyl-1H-indol-5-yloxy)-N-(3-(2-
(methylsulphonyl)ethoxy)
phenyl)pyrimidine-2-amine
(CD3OD): 8,345 (s, 1H), 8,049 (s, 1H), 7,915 (d, J=6.0 Hz, 1H), 7,826 (s, 1H), 7,58 (d, J=8,8 Hz, 1H), 7,535 (m, J=7,2-6,8 Hz, 1H), 7,433 (d, J=7,6 Hz, 2H), 7,103 (d, J=7,6 Hz, 1H), 6,241 (s, 1H), 2,460 (s, 3H); MS (m/e):402,2 (M+1)

51N-methyl(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)
methanesulfonamide
11,217 (s, 1H), 8,998 (s, 1H), 8,789 (s, 1H), 7,947 (d, J=5.6 Hz, 1H), 7,595 (m, J=7,8-1,6 Hz, 2H), 7,133 (d, J=8.0 Hz, 2H), 7,000, (s, 1H), 6,721 (d, J=2,8 Hz, 1H), 6,211 (s, 1H), 6,021 (s, 1H), 2,403 (s, 3H), 2,346 (s, 3H);
MS (m/e): 380,2 (M+1)
52N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-forfinal)pyrimidine-2,4-diamine
(CD3OD): 11,234 (s, 1H), 9,256 (s, 1H), 8,898 (s, 1H), 7,966 (d, J=5.6 Hz, 1H), 7,752 (d, J=8,4 Hz, 1H), 7,393 (t, J=8,4 Hz, 1H), 7,133 (m, J=8.4 and 3.6 Hz, 3H), 6,612 (t, J=7,6-1.2 Hz, 1H), 6,239 (s, 1H), 6,050 (s, 1H), 2,402 (s, 3H); MS (m/e): 352,2 (M+1)
53N2-(3-chlorophenyl)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 11,221 (s, 1H), 8,965 (s, 1H), 8,775 (s, 1H), 7,927 (d, J=6.0 Hz, 1H), 7,619 (d, J=8.0 Hz, 2H), 7,128 (m, J=8.0 to about 7.6 Hz, 2H), 6,958 (d, J=7.8 Hz, 2H), 6,210 (s, 1H), 2,411 (s, 3H); MS (m/e): 368,2 (m/e) (M+1)

542-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzonitrile
(CD3OD): 11,248 (s, 1H), 9,412 (s, 1H), 8,959, 1H), 8,208 (s, 1H), 7,936 (d, J=7.2 Hz, 1H), 7,562 (d, J=5.6 Hz, 1H), 7,287 (s, 2H), 7,164 (d, J=8,4 Hz, 2H), 6,233 (s, 1H), 6,075 (s, 1H), 2,399 (s, 3H); MS (m/e): 359,2 (M+1)
55N2-(3, 5dimethylphenyl)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 11,200 (s, 1H), 8,806 (s, 1H), 8,745 (s, 1H), 7,911 (d, J=6.0 Hz, 1H), 7,216 (s, 2H) 7,117 (t, J=8,8-7,8 Hz, 2H), 6,396 (s, 1H), 6,181 (s, 1H), 6,010 (s, 1H), 2,381 (s, 3H); 1,985 (s, 6H); MS (m/e): 362,3 (M+1)
56N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(2-trifluoromethyl)phenyl)
pyrimidine-2,4-diamine
(CD3OD): 11,211 (s, 1H), 8,898 (s, 1H), 8,209 (s, 1H), 7,939 (t, J=9,6 to 6.0 Hz, 2H), 7,270 (t, J=8,4-1,6 Hz, 1H) 7,126 (s, 2H), 6,998 (m, J=2.0 to 1.2 Hz, 2H), 6,225 (s, 1H), 6,035 (s, 1H), 2,402 (s, 3H); MS (m/e): 402,2 (M+1)
57N2-(2-chlorophenyl)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
(CD3OD): 11,231 (s, 1H), 8,922 (s, 1H), 8,143 (d, J=8.0 Hz, 1H), 7,936 (s, J=5.6 Hz, 1H), 7,790 (s, 1H), 7,424 (d, J=8,4 Hz, 1H), 7,101 (m, J=8.4 to 7.2 Hz, 2H), 6,993 (t, J=8,8-7,2 Hz, 1H), 6,216 (s, 1H), 6,093 (m, J=7,2-10,0 Hz, 1H), 4,043 (s, J=7.8 Hz, 1H), 2,402 (s, 3H); MS (m/e): 368,2 (M+1)

59N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(4-methoxyphenyl)pyrimidine-2,4-diamine
11,222 (s, 1H), 8,796 (s, 1H), 8,729 (s, 1H), (CD3OD): 7,959 (s, 1H), 7,892 (d, J=5.6 Hz, 1H), 7,547 (d, J=8,8 Hz, 2H) 7,075 (s, 1H), 6,646 (d, J=7,6 Hz, 2H), 6,222 (s, 1H), 5,567 (s, 1H), 3,658 (s, 3H), 2,406 (s, 3H); MS (m/e): 402,2 (M+1)
60N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(4-phenoxyphenyl)pyrimidine-2,4-diamine
(CD3OD): 11,190 (s, 1H), 9,046 (s, 1H), 8,801 (s, 1H), 7,959 (s, 1H), 7,931 (d, J=6.0 Hz, 1H), 7,681 (d, J=7.2 Hz, 2H), 7,361 (t, J=8.0 to about 7.6 Hz, 2H), 7,114 (m, J=8.4 to 7.2 Hz, 3H), 6,903 (d, J=8.0 Hz, 2H), 6,755 (d, J=7.2 Hz, 2H), 6,179 (s, 1H), 6,024 (s, 1H), 2,338 (s, 3H), MS (m/e): to 426.2 (M+1)
612-(1-(3-(4-(4-fluoro-2-methyl-1H-indol-5-
ylamino)pyrimidine-2-
ylamino)benzyl)piperidine-4-yl)ethanol
(CD3OD): 7,932 (s, 1H), 7,885 (d, J=5.6 Hz, 1H), 7,331 (m, 1H), 7,204 (m, 3H), 7,103 (t, J=7.2 Hz, 1H), 6,958 (d, J=7,6 Hz, 1H), 6,251 (s, 1H), to 6.176 (m, 1H), 3,603-3,572 (m, 4H), 3,068-3,041 (m, 2H), 2,454 (s, 3H), (m, 2H), 2,197 (user., 2H), 1,783-1,750 (m, 2H), 1,563 (user., 2H), 1,477 (m, 2H), 1,311-1,275 (m, 2H), MS (m/e): 475,4 (M+1)

62N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(3-(methylsulphonyl)propoxy)
phenyl)pyrimidine-2,4-diamine
(DMSO-d6): 7,932 (d, J=6.0 Hz, 1H), 7,399 (s, 1H), 7,393 (d, J=6,8 Hz, 1H), 7,099 (m, 2H), 6,97 (m, 1H), 6,416 (d, J=8.0 Hz, 1H), 6,207 (s, 1H), 6,088, 1H), a-3.84 (m, 2H), 3,196 (m, 2H), 3,010 (s, 3H), 2,400 (s, 3H), 2,014 (m, 2H), MS (m/e): equal to USD 470.5 (M+1)
632-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethanol
(DMSO-d6): 7,938 (d, J=6.0 Hz, 1H), 7,347 (m, 2H), 7,104 (m, 2H), 6,950 (m, 1H), 6,410 (d, J=8.0 Hz, 1H), 6,206 (s, 1H), 6,088 (s, 1H), 3,788 (m, 2H), 3,630 (m, 2H), 2,401 (s, 3H), MS (m/e): 394,4 (M+1)
64N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(piperidine-3-yloxy)phenyl)pyrimidine-2,4-diamine
(DMSO-d6): 11,241 (s, 1H), 8,966 (s, 1H), 8,789 (s, 1H), 7,929 (d, J=5.6 Hz, 1H), 7,378 (s, 1H), 7,267 (d, J=7,6 Hz, 1H), 7,120-at 7,053 (m, 2H), 6,964 (m, 1H), 6,380 (d, J=8.0 Hz, 1H) 6,207 (s, 1H), 6,010 (s, 1H), 4,010 (s, 1H), 3,710 (m, 1H); 3,554 (s, 2H), 3,362 (m, 2H), 2,506 (s, 3H), 2,401 (m, 2H) 1,234 (m, 2H), MS (m/e): 433,2 (M+1)

65N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-((1-(methylsulphonyl)
piperidine-4-yl)methoxy)
phenyl)pyrimidine-2,4-diamine
(CD3OD): 8,021 (d, J=5.6 Hz, 1H), 7,418 (s, 1H), 7,220-7,051 (m, 3H), 6,998 (m, 1H), 6,612 (d, J=7,4 Hz, 1H) 6,267 (s, 1H), 5,800 (d, J=5.6 Hz, 1H), 3,960 (d, J=5,2 Hz, 2H), 3,810 (m, 2H); 3,362 (m, 2H), 2,826 (s, 3H), 2,506 (s, 3H), 1,556 (m, 2H), 1,452 (m, 1H), 1,234 (m, 2H)
661-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)p is rimidine-2-ylamino)benzyl)piperidine-4-ol
(CD3OD): 8,247 (d, J=5.6 Hz, 1H), 7,378 (s, 1H), 7,160-7,108 (m, 2H), 6,956 (t, J=8.0 Hz, 1H), 6,895-6,825 (m, 2H), 6,450 (d, J=5.6 Hz, 1H), 6,247 (s, 1H), 3,031 (s, 1H), 2,690-2,663 (m, 2H), 2,455 (s, 3H), 2,069-2,042 (m, 2H), 1,815-1,716 (m, 2H), 1,562-1,483 (m, 2H); MS (m/e): 448,5 (M+1)
674-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(methylsulphonyl)phenyl)
pyrimidine-2-amine
(CD3OD): 8,292 (d, J=5.6 Hz, 1H), 8,005 (s, 1H), 7,691 (d, J=7.2 Hz, 1H), 7,341 (d, J=7.2 Hz, 1H), 7,102 (d, J=8,8 Hz, 1H), 7,013 (t, J=7.2 Hz, 1H), 6,849 (t, J=8.0 Hz, 1H), 6,482 (d, J=5.6 Hz, 1H), 6,221 (s, 1H), 2,900 (s, 3H), UAH 2.432 (s, 3H); MS (m/e): 413,4 (M+1)

68N-cyclopropyl-2-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)ndimethylacetamide
(DMSO-d6): 7,947 (m, 2H), 7,298 (m, 2H), 7,154 (d, J=8,4 Hz, 1H), 6,947 (m, 1H), 6,755 (m, 1H), 6,775 (d, J=8.0 Hz, 1H), 6,441 (d, J=5.6 Hz, 1H), 6,240 (s, 1H), 3,027 (s, 2H), 2,593 (m, 1H), 2,499 (s, 3H), 0,596 (m, 2H), 0,390 (m, 2H), MS (m/e): 432,5 (M+1)
69(E)-3-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)-N-methylacrylamide
(DMSO-d6): 11,550 (s, 1H), 9,791 (s, 1H), 8,385 (d, J=5,2, 1H), 8,114 (d, J=4,8, 1H), 7,432 (d, J=7,2, 2H), 7,214 (d, J=10, 1H), 7,184 (d, J=3,2, 1H), 7,083 (d, J=8, 2H), 6,942 m, J=16, 1H), 6,533 (d, J=5,6, 1H, 6,402 (d, J=15,6), 6,253 (s, 1H), 2,687 (d, J=4,8, 3H), 2,440 (s, 3H), MS (m/e): 418,2 (M+1)
703-(3-(4-(4-fluoro-2-methyl-1H-indol-5-
yloxy)pyrimidine-2-ylamino)phenyl)-N,N-dimethylpropanamide
(DMSO-d6): 11,397 (s, 1H), 9,420 (s, 1H), 8,334 (d, J=5,6, 1H), 7,290 (s, 1H), 7,241 (d, J=7,2, 1H), 7,152 (d, J=8,8, 1H), 6,919 (m, J=15,2, 1H), 6,803 (m, J=15,6, 1H), 6,652 (d, J=6,8, 1H), 6,451 (d, J=5,6, 1H), 6,218 (s, 1H), 2,860 (s, 3H), 2,795 (s, 3H), 2,449 (m, J=14,8, 2H), 2,399 (s, 3H), 2,338 (m, J=14,8, 2H), MS (m/e): 434,2 (M+1)

71N-methyl-3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzamide
MS (m/e): 372,4 (M)
72N2-(2-forfinal)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 350,1 (M+1)
733-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzonitrile
MS (m/e): 341,2(M+1)
74N4-(2-methyl-1H-indol-5-yl)-N2-(3-(methylthio)
phenyl)pyrimidine-2,4-diamine
MS (m/e): 362,3 (M+1)

75N,N-dimethyl-3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzosulfimide
MS (m/e): 423,5 (M+1)
76N4-(2-methyl-1H-indol-5-yl)-N2-(3-(morpholinomethyl)
phenyl)pyrimidine-2,4-diamine
MS (m/e): 465,4 (M+1)
77N2-(3,4-acid)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 376.3 on(M+1)
78N2-(4-chlorophenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 350,3 (M+1)
79N2-(2,4-differenl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 352,2 (M+1)

80N2-(3-chloro-2-forfinal)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 368,3 (M+1)
81N2-(1H-indol-4-yl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-d is Amin
MS (m/e): 355,3 (M+1)
82N2-(4-(3-(dimethylamino)
propoxy)phenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 417,4 (M+1)
832-(4-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-
ylamino)phenoxy)ethanol
MS (m/e): 376.3 on(M+1)
84N2-(3-chloro-4-forfinal)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 368,3 (M+1)

85N2-(benzo[d][1,3]-dioxol-5-yl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 360,3 (M+1)
86(1-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)
piperidine-4-yl)methanol
MS (m/e): 443,4 (M+1)
87N4-(2-methyl-1H-indol-5-yl)-N2-(3-(2-(4-(methylsulphonyl)
piperazine-1-yl)ethoxy)phenyl)pyrimidine-2,4-diamine
MS (m/e): 521,2 (M)
883-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-
propylbenzenesulfonyl
MS (m/e): 437,3 (M+1)
89N2-(2-chloro-4-forfinal)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 368,1 (M+1)

902-chloro-4-fluoro-5-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-
ylamino)phenol
MS (m/e): 384,3 (M+1)
91N2-(4-chloro-2-forfinal)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 368,3 (M+1)
92N2-(3-(2-(dimethylamino)ethoxy)
phenyl)-N4-(2-methyl-1H-indol-5-yl)-pyrimidine-2,4-diamine
MS (m/e): 403,4 (M+1)
93N2-(2-methyl-1H-indol-5-yl)-N4-(3-(3-(methylsulphonyl)
propoxy)phenyl)pyrimidine-2,4-diamine
MS (m/e): 452,3(M+1)
94MS (m/e): 457,4 (M+1)
95N4-(2-methyl-1H-indol-5-yl)-N2-(3-(piperidine-4-
ylethoxy)phenyl)
pyrimidine-2,4-diamine
MS (m/e): 429,4 (M+1)

96N4-(2-methyl-1H-indol-5-yl)-N2-(3-(piperidine-3-yloxy)phenyl)pyrimidine-
2,4-diamine
MS (m/e): 416,4 (M+1)
971-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)
piperidine-4-ol
MS (m/e): 429,4 (M+1)
98(S)-N4-(2-methyl-1H-indol-5-yl)-N2-(3-(pyrrolidin-3-yloxy)phenyl)pyrimidine-
2,4-diamine
MS (m/e): 401,4 (M+1)
99(S)-N4-(2-methyl-1H-indol-5-yl)-N2-(3-(1-(methylsulphonyl)
pyrrolidin-3-yloxy)phenyl)pyrimidine-2,4-diamine
MS (m/e): 479,5 (M+1)
100N4-(2-methyl-H-indol-5-yl)-N2-(3-(piperidine-4-yloxy)phenyl)pyrimidine-2,4-diamine
MS (m/e): 415,5 (M+1)

101N4-(2-methyl-1H-indol-5-yl)-N2-(3-(3-(4-(methylsulphonyl)
piperazine-1-yl)-propoxy)phenyl)
pyrimidine-2,4-diamine
MS (m/e): 536,6 (M+1)
102N4-(2-methyl-1H-indol-5-yl)-N2-(3-(3-morpholinoethoxy)phenyl)
pyrimidine-2,4-diamine
MS (m/e): 459,6 (M+1)
103(R)-N4-(2-methyl-1H-indol-5-yl)-N2-(3-(1-(methylsulphonyl)
pyrrolidin-3-yloxy)phenyl)pyrimidine-2,4-diamine
MS (m/e): 479,5 (M+1)
104(E)-N,N-dimethyl-3-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)acrylamide
MS (m/e): 413,2 (M+1)
1054-(4-fluoro-2-methyl-1H-indol-5-yl)-N-(3-(3-(thiomorpholine-1',1'-dioxide)propoxy)phenyl)
pyrimidine-2-amine
MS (m/e): are 507, 5 (M+1)

106 N4-(2-methyl-1H-indol-5-yl)-N2-(3-(2-(methylamino)ethoxy)
phenyl)pyrimidine-2,4-diamine
MS (m/e): to 389.5 (M+1)
1074-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(3-(thiomorpholine-1'-oxide)propoxy)phenyl)
pyrimidine-2-amine
MS (m/e): 491,5 (M+1)
108N-(2-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethyl)
methanesulfonamide
MS (m/e): 453,4 (M+1)
109N4-(2-methyl-1H-indol-5-yl)-N2-(3-(3-thiomorpholine)
phenyl)pyrimidine-2,4-diamine
MS (m/e): 475,5 (M+1)
110trifter-N-(4-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)
methanesulfonamide
MS (m/e): 463,4 (M+1)

111N4-(2-methyl-1H-indol-5-yl)-N2-(3-(2-thiomorpholine)
phenyl)pyrimidine-2,4-diamine
MS (m/e): 461,4 (M+1)
112 N4-(2-methyl-1H-indol-5-yl)-N2-(3-(2-pyrrolidinone)phenyl)
pyrimidine-2,4-diamine
MS (m/e): 429,4(M+1)
113N4-(2-methyl-1H-indol-5-yl)-N2-(3-(2-morpholinoethyl)
phenyl)pyrimidine-2,4-diamine
MS (m/e): 493,1 (M+1)
114N4-(2-methyl-1H-indol-5-yl)-N2-(3-(2-(pyrrolidin-1-yl)ethylsulfonyl)phenyl)
pyrimidine-2,4-diamine
MS (m/e): 477,1 (M+1)
115N4-(2-methyl-1H-indol-5-yl)-N2-(3-((4-(methylsulphonyl)
piperazine-1-yl)methyl)phenyl)
pyrimidine-2,4-diamine
MS (m/e): 492,4 (M+1)

1162-(4-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)
piperazine-1-yl)ethanol
MS (m/e): 458,5 (M+1)
117N4-(2-methyl-1H-indol-5-yl)-N2-(3-(methylsulfonylmethyl)
phenyl)pyrimidine-2,4-diamine
MS (m/e): 408,3 (M+1)
118MS (m/e): 415,5 (M+1)
119(E)-N-methyl-3-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)acrylamide
MS (m/e): 399,2 (M+1)
120N4-(2-methyl-1H-indol-5-yl)-N2-(3-(tetrahydro-2H-Piran-4-yloxy)phenyl)pyrimidine-2,4-diamine
MS (m/e): 416,4 (M+1)

121N2-(3-(2-aminoethoxy)phenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 375,3 (M+1)
122N-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)
methanesulfonamide
MS (m/e): 423,4 (M+1)
123N-(2-hydroxyethyl)-3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzamide
MS (m/e): 403,2 (M+1)
124N-methyl-3-(3-(4-(2-methyl-1H-indol-5-ylamino)PIR is midin-2-ylamino)phenyl)propanamide
MS (m/e): 401,2 (M+1)
1253-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-(methylamino)-2-oxoethyl)benzamide
MS (m/e): 430,2 (M+1)

1263-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-morpholinoethyl)benzamide
MS (m/e): 472,3 (M+1)
1273-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-(piperidine-1-yl)ethyl)benzamide
MS (m/e): 470,1 (M+1)
128trifter-N-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)
methanesulfonamide
MS (m/e): 463,0 (M+1)
129N-(2-methoxyethyl)-3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzamide
MS (m/e): 417,2 (M+1)
130N-(4-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)
methanesulfonamide
MS (m/e): 409,1 (M+1)

1312-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)-N-(2-morpholinoethyl)ndimethylacetamide
MS (m/e): 493,1 (M+1)
132N2-(6-methoxypyridine-3-yl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 347,4 (M+1)
1332-methyl-N-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-yl)-1H-indol-5-amine
MS (m/e): 370,3 (M+1)
134N-(3-(3-(dimethylamino)propoxy)
phenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine
MS (m/e): 418,4 (M+1)
1352-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenoxy)ethanol
MS (m/e): 377,4 (M+1)

136N-(3-(2-(dimethylamino)ethoxy)
phenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine
MS (m/e): 404,4 (M+1)
137N-cyclopropyl-2-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)ndimethylacetamide
MS (m/e): 414,4 (M+1)
1384-(2-methyl-1H-indol-5-yloxy)-N-(3-(3-(methylsulphonyl)
propoxy)phenyl)
pyrimidine-2-amine
MS (m/e): 453,4 (M+1)
1394-(2-methyl-1H-indol-5-yloxy)-N-(3-(piperidine-4-ylethoxy)phenyl)
pyrimidine-2-amine
MS (m/e): USD 448,2 (M+1)
1404-(2-methyl-1H-indol-5-yloxy)-N-(3-(piperidine-3-yloxy)phenyl)pyrimidine-2-amine
MS (m/e): 416,2 (M+1)

1414-(2-methyl-1H-indol-5-yloxy)-N-(3-(piperidine-4-yloxy)phenyl)
pyrimidine-2-amine
MS (m/e): 416,4 (M+1)
1424-(2-methyl-1H-indol-5-yloxy)-N-(3-(1-(methylsulphonyl)
piperidine-4-yloxy)phenyl)pyrimidine-2-amine
MS (m/e): of 494.5 (M+1)
1431-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)
piperidine-4-ol
MS (m/e): 430,4 (M+1)
144(1-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)
piperidine-4-yl)methanol
MS (m/e): 444,4 (M+1)
1452-(1-(3-(4-(2-methyl-1H-indol-5-yloxy)
pyrimidine-2-ylamino)
benzyl)piperidine-4-yl)ethanol
MS (m/e): 458,5 (M+1)

/tr>
146N-(3-(4-(2-methyl-1H-indol-5-yloxy)
pyrimidine-2-ylamino)
phenyl)methanesulfonamide
MS (m/e): 409,12 (M+1)
147(S)-4-(2-methyl-1H-indol-5-yloxy)-N-(3-(1-(methylsulphonyl)
pyrrolidin-3-yloxy)phenyl)pyrimidine-2-amine
MS (m/e): 480,5 (M+1)
148(E)-N,N-dimethyl-3-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)acrylamide
MS (m/e): 414,5 (M+1)
1493-(3-(4-(2-methyl-1H-indol-5-yloxy)
pyrimidine-2-ylamino)phenyl)-1-morpholinopropan-1-it
MS (m/e): 458,5 (M+1)
150N-(3-(2-methoxyethoxy)phenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine
MS (m/e): 391,0 (M+1)

1514-(2-methyl-1H-indol-5-yloxy)-N-(3-(morpholinomethyl)
phenyl)pyrimidine-2-amine
MS (m/e): 465,1 (M+1)
152N-(2-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenoxy)ethyl)
methanesulfonamide
MS (m/e): 454,2 (M+1)
153(R)-4-(2-methyl-1H-indol-5-yloxy)-N-(3-(1-(methylsulphonyl)
pyrrolidin-3-yloxy)phenyl)pyrimidine-2-amine
MS (m/e): 480,5 (M+1)
1544-(2-methyl-1H-indol-5-yloxy)-N-(3-(2-morpholinoethoxy)phenyl)
pyrimidine-2-amine
MS (m/e): KZT 446.4 (M+1)
155N-(2-(dimethylamino)
ethyl)-3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzamide
MS (m/e): 431,4 (M+1)

156N-(3-(2-methoxyethoxy)phenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine
MS (m/e): 391,3 (M+1)
1574-(2-methyl-1H-indol-5-yloxy)-N-(3-(morpholinomethyl)phenyl)
pyrimidine-2-amine
MS (m/e): 416,4 (M+1)
1584-(2-methyl-1H-indol-5-yloxy)-N-(3-(3-thiomorpholine)
phenyl)pyrimidine-2-amine
MS (m/e): 476,5 (M+1)
159N-(3-(2-(dimethylamino)
ethylsulfonyl)phenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine
MS (m/e): 452,4 (M+1)
1604-(2-methyl-1H-indol-5-yloxy)-N-(3-(2-morpholinoethyl)
phenyl)pyrimidine-2-amine
MS (m/e): 494,4 (M+1)

1614-(2-methyl-1H-indol-5-yloxy)-N-(3-(2-(pyrrolidin-1-yl)ethylsulfonyl)phenyl)
pyrimidine-2-amine
MS (m/e): 478,4 (M+1)
1624-(2-methyl-1H-indol-5-yloxy)-N-(3-(2-thiomorpholine)
phenyl)pyrimidine-2-amine
MS (m/e): 462,4 (M+1)
1634-(2-methyl-1H-indol-5-yloxy)-N-(3-(2-(pyrrolidin-1-yl)ethoxy)phenyl)
pyrimidine-2-amine
MS (m/e): 430,3 (M+1)
1644-(2-methyl-1H-indol-5-yloxy)-N-(3-((4-(methylsulphonyl)
piperazine-1-yl)methyl)
phenyl)pyrimidine-2-amine
MS (m/e): 493,5 (M+1)
1652-(4-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)
piperazine-1-yl)ethanol
MS (m/e): 459,5 (M+1)

1664-(2-methyl-1H-indol-5-yloxy)-N-(3-((tetrahydro-2H-Piran-4-yl)methoxy)phenyl)
pyrimidine-2-amine
MS (m/e): that amount to 431,3 (M+1)
1674-(2-methyl-1H-indol-5-yloxy)-N-(3-(methylsulfonylmethyl)
phenyl)pyrimidine-2-amine
MS (m/e): 409,4 (M+1)
168tert-butyl 4-(2-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenoxy)ethyl)
piperazine-1-carboxylate
MS (m/e): 545,4(M+1)
169N,N-dimethyl-3-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino))phenyl)
propanamide
MS (m/e): 416,5 (M+1)
170(E)-N-methyl-3-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)acrylamide
MS (m/e): 400,2 (M+1)

1714-(2-methyl-1H-indol-5-yloxy)-N-(3-(tetrahydro-2H-Piran-4-yloxy)phenyl)pyrimidine-2-amine
MS (m/e): 416,18 (M+1)
172N-(3-(2-aminoethoxy)
phenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine
MS (m/e): 376.3 on (M+1)
173N-(3-(4-(2-methyl-1H-indol-5-yloxy)
pyrimidine-2-ylamino)
benzyl)methanesulfonamide
MS (m/e): 424,4 (M+1)
174N-(2-hydroxyethyl)-3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzamide
MS (m/e): 404,1 (M+1)
1754-(2-methyl-1H-indol-5-yloxy)-N-(3-(2-(piperazine-1-yl)ethoxy)phenyl)
pyrimidine-2-amine
MS (m/e): 444,5 (M)

1763-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-(2-(methylamino)-2-oxoethyl)benzamide
MS (m/e): 431,2 (M+1)
1773-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-(2-morpholinoethyl)benzamide
MS (m/e): 473,0 (M+1)
1783-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-(2-(piperidine-1-yl)ethyl)benzamide
MS (m/e): 471,4 (M+1)
179 N-methyl-3-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino))phenyl)
propanamide
MS (m/e): 402,2 (M+1)
180N-(2-methoxyethyl)-3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzamide
MS (m/e): 418,1 (M+1)

181N-(4-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)
methanesulfonamide
MS (m/e): 410,2 (M+1)
1822-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)-N-(2-morpholinoethyl)ndimethylacetamide
MS (m/e): 487,1 (M+1)
1834-(2-methyl-1H-indol-5-yloxy)-N-(3-(2-(methylsulphonyl)ethoxy)
phenyl)pyrimidine-2-amine
MS (m/e): 439,2 (M+1)
184N-methyl(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)
methanesulfonamide
MS (m/e): 424,4 (M+1)
185N-(6-methoxypyridine-3 is)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine
MS (m/e):348,2 (M+1)

186methyl 2-(4-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)acetate
MS (m/e): 406,2 (M+1)
187N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(2-methoxyphenyl)pyrimidine-2,4-diamine
MS (m/e): 364,2 (M+1)
188N2-(3-bromophenyl)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 412,3 (M+1)
189N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(methylsulphonyl)phenyl)
pyrimidine-2,4-diamine
MS (m/e): 412,3 (M+1)

1903-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzonitrile
MS (m/e): 359,3 (M+1)
191N2-(2-chloro-4-forfinal)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 386,2 (M+1)
192N-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)
methanesulfonamide
MS (m/e): 427,3 (M+1)
193N2-(3,4-differenl)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 370,2 (M+1)
194N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(2-morpholinoethoxy)phenyl)
pyrimidine-2,4-diamine
MS (m/e): 463,4 (M+1)

195N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(2-(4-(methylsulphonyl)
piperazine-1-yl)ethoxy)phenyl)pyrimidine-2,4-diamine
MS (m/e): 540,3 (M+1)
196N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(2-(2-morpholinoethoxy)phenyl)
pyrimidine-2,4-diamine
MS (m/e): 462,3 (M)
197N2-(3-(3-(dimethylamino)
propoxy)phenyl)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 435,4 (M+1)
198N-cyclopropyl-2-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)ndimethylacetamide
MS (m/e): 431,4 (M+1)

199N-(2-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethyl)
methanesulfonamide
MS (m/e): 471,4 (M+1)
2002-(2-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethanol
MS (m/e): 394,4 (M+1)
201N2-(3-(2-(dimethylamino)ethoxy)
phenyl)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 421,4 (M+1)
202(1-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)
piperidine-4-yl)methanol
MS (m/e): 461,5 (M+1)
2033-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-methylbenzamide
MS (m/e): 391,3 (M+1)

204trifter-N-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)
methanesulfonamide
MS (m/e): 481,3 (M+1)
205N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(piperidine-4-ylethoxy)phenyl)
pyrimidine-2,4-diamine
MS (m/e): 446,22 (M+1)
206(E)-3-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)-1-morpholinopropan-2-EN-1-it
MS (m/e): 473,5 (M+1)
207trifter-N-(4-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)
methanesulfonamide
MS (m/e):481,3 (M+1)
208N-(5-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)pyridine-2-yl)ndimethylacetamide
MS (m/e): 392,4 (M+1)

209N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(Mohali sulfonyl)
phenyl)pyrimidine-2,4-diamine
MS (m/e): 483,5 (M+1)
2103-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-methylbenzenesulfonamide
MS (m/e): 427,1 (M+1)
211N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(2-methoxyethoxy)phenyl)
pyrimidine-2,4-diamine
MS (m/e): 408,4 (M+1)
2124-(4-fluoro-2-methyl-1H-indol-5-yl)-N-(3-(3-(thiomorpholine-1',1'-dioxide)propoxy)phenyl)
pyrimidine-2-amine
MS (m/e): 525,5 (M+1)
213N-(2-(dimethylamino)ethyl)-3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzamide
MS (m/e): 448,5 (M+1)

214N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(2-(methylamino)ethoxy)
phenyl)pyrimidine-2,4-diamine
MS (m/e): of 407.5 (M+1)
215(E)-3-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimid is n-2-ylamino)phenyl)-1-morpholinopropan-2-EN-1-it
MS (m/e): 473,1 (M+1)
216N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(3-thiomorpholine)
phenyl)pyrimidine-2,4-diamine
MS (m/e): 493,5 (M+1)
217N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(2-morpholinoethyl)
phenyl)pyrimidine-2,4-diamine
MS (m/e): 511,4 (M+1)
218N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(2-thiomorpholine)
phenyl)pyrimidine-2,4-diamine
MS (m/e): 479,4 (M+1)

219N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(2-(pyrrolidin-1-yl)ethoxy)phenyl)
pyrimidine-2,4-diamine
MS (m/e): 447,4 (M+1)
220N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-((4-(methylsulphonyl)
piperazine-1-yl)methyl)phenyl)
pyrimidine-2,4-diamine
MS (m/e): 510,4 (M+1)
2212-(4-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-the laminitis)benzyl)
piperazine-1-yl)ethanol
MS (m/e): 474,7 (M-1)
2223-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)
phenylmethanesulfonyl
MS (m/e): 428,4 (M+1)
223N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(methylsulfonylmethyl)
phenyl)pyrimidine-2,4-diamine
MS (m/e): 426,4 (M+1)

224tert-butyl 4-(2-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethyl)
piperazine-1-carboxylate
MS (m/e): 544,4 (M+1)
225tert-butyl 4-(2-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethyl)
piperazine-1-carboxylate
MS (m/e): 562,3 (M+1)
2263-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino))phenyl)-N,N-dimethylpropanamide
MS (m/e): 433,4 (M+1)
227(E)-3-(3-(4-(4-f the PR-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)-N-methylacrylamide
MS (m/e): 417,2 (M+1)
228N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-((tetrahydro-2H-Piran-4-yl)methoxy)phenyl)
pyrimidine-2,4-diamine
MS (m/e): 448,4 (M+1)

229N2-(3-(2-aminoethoxy)phenyl)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
MS (m/e): 393,2 (M+1)
230N-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)
methanesulfonamide
MS (m/e): 441,4 (M+1)
2313-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-hydroxyethyl)benzamide
MS (m/e): UAH 421,2 (M+1)
2323-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-morpholinoethyl)benzamide
MS (m/e): 490,1 (M+1)

2333-(4-(4-fluoro-2-methyl-1H-indol-5-yl) - Rev. Ino)pyrimidine-2-ylamino)-N-(2-(piperidine-1-yl)ethyl)benzamide
MS (m/e): 488,4 (M+1)
2343-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)-N-methylpropanamide
MS (m/e): 419,2 (M+1)
2353-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-methoxyethyl)benzamide
MS (m/e): 435,2 (M+1)
236N-(4-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)
methanesulfonamide
MS (m/e): 427,2 (M+1)
2372-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)-N-(2-morpholinoethyl)ndimethylacetamide
MS (m/e): 504,1 (M+1)

2383-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-(methylamino)-2-oxoethyl)benzamide
MS (m/e): USD 448,2 (M+1)
239N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(tetrahydro-2H-Piran-4-yloxy)phenyl)Piri is one-2,4-diamine
MS (m/e): 434,4 (M+1)
2401-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)
sulfonylmethane
MS (m/e): 441,4 (M+1)
241N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(6-methoxypyridine-3-yl)pyrimidine-2,4-diamine
MS (m/e): 365,4 (M+1)

2424-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(2-morpholinoethoxy)phenyl)
pyrimidine-2-amine
MS (m/e): 464,4 (M+1)
2434-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(3-morpholinoethoxy)phenyl)
pyrimidine-2-amine
MS (m/e): 478,4 (M+1)
2442-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenoxy)ethanol
MS (m/e): 395,4 (M+1)
2454-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(3-(thiomorpholine-1',1'-dioxide)propoxy)phenyl)
pyrimidine-2-amine
MS (m/e): 526,7 (M+1)
246(R)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(pyrrolidin-3-yloxy)phenyl)pyrimidine-2-amine
MS (m/e): 420,5 (M+1)

247(S)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(pyrrolidin-3-yloxy)phenyl)pyrimidine-2-amine
MS (m/e): 420,5 (M+1)
2484-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(1-(methylsulphonyl)piperidine-4-yloxy)phenyl)
pyrimidine-2-amine
MS (m/e): 512,4 (M+1)
249(R)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(1-(methylsulphonyl)
pyrrolidin-3-yloxy)phenyl)pyrimidine-2-amine
MS (m/e): 498,4 (M+1)
250N-(2-(dimethylamino)
ethyl)-3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzamide
MS (m/e): 448,5 (M+1)
251(1-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)
piperidin the-4-yl)methanol
MS (m/e): 462,4 (M+1)

2522-(1-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)
piperidine-4-yl)ethanol
MS (m/e): 476,5 (M+1)
2534-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(2-(methylamino)ethoxy)phenyl)
pyrimidine-2-amine
MS (m/e): 408,4 (M+1)
254(E)-3-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)-1-morpholinopropan-2-EN-1-it
MS (m/e): 474,5 (M+1)
2554-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(morpholinomethyl)phenyl)
pyrimidine-2-amine
MS (m/e): 434,5 (M+1)
256(S)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(1-(methylsulphonyl)
pyrrolidin-3-yloxy)phenyl)pyrimidine-2-amine
MS (m/e): 498,4 (M+1)

2573-(4-(4-f the PR-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-methylbenzamide
MS (m/e): 392,4 (M+1)
258N-(2-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenoxy)ethyl)
methanesulfonamide
MS (m/e): 472,4 (M+1)
259trifter-N-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-Ilmenau)phenyl)
methanesulfonamide
MS (m/e): 482,3 (M+1)
2604-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(3-thiomorpholine)
phenyl)pyrimidine-2-amine
MS (m/e): of 494.5 (M+1)

2614-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(2-(pyrrolidin-1-yl)ethylsulfonyl)phenyl)
pyrimidine-2-amine
MS (m/e): 496,4 (M+1)
2624-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(2-morpholinoethyl)
phenyl)pyrimidine-2-amine
MS (m/e): 512,4 (M+1)
2634-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(2-timehole is metoxi)
phenyl)pyrimidine-2-amine
MS (m/e): 480,4 (M+1)
2644-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(2-(pyrrolidin-1-yl)ethoxy)phenyl)
pyrimidine-2-amine
MS (m/e): 448,4 (M+1)
2654-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-((4-(methylsulphonyl)
piperazine-1-yl)methyl)
phenyl)pyrimidine-2-amine
MS (m/e): 511,4 (M+1)

2662-(4-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)
piperazine-1-yl)ethanol
MS (m/e): 477,5 (M+1)
2674-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-((tetrahydro-2H-Piran-4-yl)methoxy)phenyl)
pyrimidine-2-amine
MS (m/e): 449,4 (M+1)
268trifter-N-(4-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)
methanesulfonamide
MS (m/e): 482,3 (M+1)
269tert-b is Teal, 4-(2-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenoxy)ethyl)
piperazine-1-carboxylate
MS (m/e): 563,4 (M+1)
2704-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(tetrahydro-2H-Piran-4-yloxy)phenyl)pyrimidine-2-amine
MS (m/e):435,4 (M+1)

271N-(3-(2-aminoethoxy)
phenyl)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine
MS (m/e): 394,4 (M+1)
272N-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)
methanesulfonamide
MS (m/e): 442,4(M+1)
2733-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-(2-hydroxyethyl)benzamide
MS (m/e): 422,1 (M+1)
2743-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-(2-(methylamino)-2-oxoethyl)benzamide
MS (m/e): 449,5 (M+1)
2753-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-(-morpholinoethyl)benzamide
MS (m/e): 491,1 (M+1)

276N-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)
methanesulfonamide
MS (m/e): 428,1 (M+1)
2773-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-(2-(piperidine-1-yl)ethyl)benzamide
MS (m/e): 489,1 (M+1)
2783-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)-N-methylpropanamide
MS (m/e): 420,2 (M+1)
2793-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-(2-methoxyethyl)benzamide
MS (m/e): 436,1 (M+1)

280N-(4-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)
methanesulfonamide
MS (m/e): 428,1 (M+1)
2812-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylox is)pyrimidine-2-ylamino)phenyl)-N-(2-morpholinoethyl)ndimethylacetamide
MS (m/e): 505,1 (M+1)
2824-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(2-(methylsulphonyl)ethoxy)
phenyl)pyrimidine-2-amine
MS (m/e): 457,2 (M+1)
2834-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(6-methoxypyridine-3-yl)pyrimidine-2-amine
MS (m/e): 366,4 (M+1)

Example 284:Synthesis of 3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenol (compound 284)

A solution of N2-(3-methoxyphenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine (0.1 mmol) in 5 ml of CH2Cl2put in an ice bath. To it add BBr3(0.5 mmol). The reaction mixture was stirred over night at room temperature, then poured into ice water, extracted with ethyl acetate. The organic layer is washed successively with water and saturated salt solution, dried over anhydrous Na2SO4and concentrate. The residue is purified by column chromatography to give the desired product with a yield of 83%.

1H NMR (DMSO-d6, 400 MHz): δ 10,501 (s, 1H), 9,115 (s, 1H), 8,956 (s, 1H), 8,868 (s, 1H), 7,908 (d, J=6 Hz, 1H), 7,716 (s, 1H), 7,271 (d, J=8 Hz, 1H), 7,210 (d, J=8,4 Hz, 1H), 7,114 (d, J=8 Hz, 1H), 6,968 (t, J=8 Hz, 1H), ,322 (DD, J=8, 1.6 Hz, 1H), 6,097 (m, 2H), 2,377 (s, 3H); MS (m/e): 331,4 (M+1).

Examples 285-295: Synthesis of compounds 285-295

Connection 285-295, each synthesized in a manner similar to that described in example 284.

ConnectionName1H NMR (CD3OD, 400 MHz)/MS
2854-(5-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-1H-pyrazole-3-yl)phenol
7,863 (d, J=6.0 Hz, 1H), 7,286 (d, J=8,8 Hz, 1H), 6,830 (user., 2H), 6,125-6,080 (m, 4H), 5,558-5,527 (m, 2H), 2,415 (s, 3H); MS (m/e): 411,8 (M+1)

2862-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenol
7,791 (d, J=6.0 Hz, 2H), 7,584 (s, 1H), 7,047 (d, J=8,8 Hz, 1H), 7,063 (d, J=7,6 Hz, 1H), 6,974 (t, J=7,6 Hz, 1H), 6,882 (d, J=8.0 Hz, 1H), 6,794 (t, J=8.0 Hz, 1H), 6,164 (d, J=6.0 Hz, 1H), 6,124 (s, 1H), 2,027 (s, 3H); MS (m/e): 332,2 (M+1)
2874-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenol
10,573 (s, 1H), 9,162 (s, 1H), 9,007 (s, 1H), 8,985 (s, 1H), 7,952 (d, J=5.6 Hz, 1H), 7,766 (s, 1H), 7,301 (d, J=8 Hz, 1H), UAH 7,262 (d, J=8 Hz, 1H), 7,123 (d, J=8 Hz, 1H), 7,011 (m, 1H), 6,332 (DD, J=8, 1.6 to the C, 1H), 6,103 (m, 2H), 2,391 (s, 3H); MS (m/e): 331,4 (M+1)
2894-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenol
8,133 (d, J=6.0 Hz, 1H), 7,324 (d, J=8,4 Hz, 1H), 7,225-7,183 (m, 3H), 6,819 (DD, J=8,8 Hz, J=2.4 Hz, 1H), 6,533 (s, 1H), 6,530 (s, 1H), 6,213 (d, J=5.6 Hz, 1H), 6,172 (s, 1H), 2,428 (s, 3H); MS (m/e): 374,3 (M+1)

2903-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenol
8,179 (d, J=6.0 Hz, 1H), 7,333 (d, J=8,8 Hz, 1H), 7,193 (s, 1H), 7,095 (s, 1H), 6,953 (d, J=7.2 Hz, 1H), 6,902 (t, J=8.0 Hz, 1H), 6,831 (d, J=8,8 Hz, 1H), 6,387 (d, J=7,6 Hz, 1H), 6,244 (d, J=6.0 Hz, 1H), 6,171 (s, 1H), 3,332 (s, 3H), 2,454 (s, 3H); MS (m/e): 333,2 (M+1)
2912-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)
pyrimidine-2-ylamino)phenol
11,249 (s, 1H), 8,943 (d, J=4,8 Hz, 1H), of 7.920 (d, J=5.6 Hz, 1H), 7,867 (m, J=6,4 Hz, 2H), 7,128 (d, J=8.0 Hz, 1H), 7,078 (t, J=8,4-6,8 Hz, 1H), 6,797 (s, 2H), 6,589 (s, 1H), 6,217 (s, 1H), 6,075 (s, 1H), 4,061 (m, J=7,2-6,8 Hz, 1H) 2,406 (s, 3H); MS: 350,2 (M+1)
2924-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)
pyrimidine-2-ylamino)phenol
11,212 (s, 1H), 8,845 (s, 1H), 8,689 (d, J=10.0 Hz, 1H), 7,868 (d, J=5.6 Hz, 2H), 7,427 (d, J=8,4 Hz, 2H), 7,10 (t, J=8.4 to 6.4 Hz, 1H), 6,509 (d, J=8.0 Hz, 2H), 6,208 (s, 1H), 5,940 (m, J=3,6-1,6 Hz, 1H), 4,060 (m, J=7,2-6,8 Hz, 1H), 2,408 (s, 3H) MS (m/e): 350,2 (M+1)
2933-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenol
11,217 (s, 1H), 9,069 (s, 1H), 8,836 (s, 1H), 8,715 (s, 1H), 7,922 (d, J=6.0 Hz, 1H), 7,224 (d, J=8,4 Hz, 2H), 7,128 (t, J=6,4 and 2.4 Hz, 2H), 6,839 (t, J=8.4 to 6.4 Hz, 1H), 6,268 (d, J=1.6 Hz, 2H), 6,249 (s, 1H), 6,207 (s, 1H), 4,043 (m, J=7,2-6,8 Hz, 1H), 2,400 (s, 3H); MS (m/e): 350,2 (M+1)

2943-(4-(2-methylbenzo-[d]oxazol-6-ylamino)pyrimidine-2-ylamino)phenol
9,500 (s, 1H), 9,175 (s, 1H), 9,054 (s, 1H), 8,164 (s, 1H), 8,003 (d, J=6.0 Hz, 1H), 7,569 (m, 2H), 7,230 (m, 2H), 6,996 (DD, 1H), 6,338 (d, J=8.0 Hz, 1H), 7,239 (d, J=6.0 Hz, 1H), 2,607 (s, 3H), MS (m/e): 334,2 (M+1)
2953-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-pyrimidine-2-ylamino)-phenol
MS (m/e): 351,4 (M+1)

Example 296: Synthesis of N-(2-methoxypyridine-4-yl)-N-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine (compound 296):

A solution of 2-chloropyrimidine-4-amine (1 mmol) and sodium methoxide (1.5 mmol) in 10 ml of methanol is heated under reflux for 2 hours, after the removal process is Italia the residue is dissolved in CH 2Cl2and washed with water, dried over anhydrous Na2SO4concentrate in vacuo to obtain 2-methoxypyridine-4-amine.

Connection 296

To a solution of 2-methoxypyridine-4-amine (0.1 mmol) and N-(2-chloropyrimidine-4-yl)-2-methyl-1H-indol-5-amine (0.1 mmol) in 3 ml of dioxide add CsCO3(0.2 mmol), Pd(OAc)2(10 mmol%) and Xantphos (10 mmol%). The mixture is stirred under microwave irradiation at 200°C for 40 minutes. After cooling the solution is filtered, and the filtrate was concentrated in vacuo, the residue is purified by column chromatography (C-18) to obtain N-(2-methoxypyridine-4-yl)-N-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine (yield 48%).

1H NMR (DMSO-d6, 400 MHz): 10,839 (s, 1H), 9,718 (s, 1H), 9,281 (s, 1H), 8,162 (d, J=6.0 Hz, 1H), 8,032 (m, 2H), 7,693 (s, 1H), 7,251 (d, J=8,8 Hz, 1H), 7,099 (d, J=7.2 Hz, 1H), 6,300 (d, J=6.0 Hz, 1H), 6,107 (s, 1H), 3,863 (s, 3H), 2,383 (s, 3H); MS (m/e): 348,2 (M+1)

Examples 297-299: Synthesis of compounds 297-299

Connection 297-299, each synthesized in a manner similar to that described in example 296.

ConnectionName1H NMR (DMSO-d6, 400 MHz)/MS
297N-(2-methoxypyridine-4-yl)-N-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
10,837 (s, 1H), 9,421 (s, 1H), 9,144 (s, 1H), 7,978 (d, J=6.0 Hz, 1H), 7,838 (d, J=6.0 Hz, 1H), 7,606 (s, 1H), 7,333-7,303 (m, 2H), 7,249 (d, J=8,4 Hz, 1H), 7,084 (d, J=8.0 Hz, 1H), 6,205 (d, J=5.6 Hz, 1H), 6,088 (, 1H), KZT 3,775 (s, 3H), KZT 2,382 (s, 3H); MS (m/e): 347,2 (M+1)
298N-(2-methoxypyridine-4-yl)-N-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
11,258 (s, 1H), 10,400 (user., 1H), 9,036 (s, 1H), 8,829 (s, 1H), 8,509 (s, 1H), 8,048 (d, J=8,4 Hz, 1H), 7,911 (d, J=5.6 Hz, 1H), 7,007-7,122 (m, 2H), 6,743 (DD, J=8,4 Hz, 1.6 Hz, 1H), 6,194 (s, 1H), 6,012 (user., 1H), 3,166 (s, 3H), 2,397 (s, 3H); MS (m/e): 428,1 (M+1)
299N-(5-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)pyridine-2-yl)methanesulfonamide
MS (m/e): 411,4 (M+1)

Example 300: Synthesis of N-(2-(4-pertenece)pyrimidine-4-yl)-2-methyl-1H-indol-5-amine (compound 300)

Connection 300

N-(2-chloropyrimidine-4-yl)-2-methyl-1H-indol-5-amine (0.1 mmol) and p-terfenol (0.1 mmol) dissolved in 0.5 ml of DMF. To it add K2CO3(0.2 mmol). After stirring at 60°C for 5 hours, the reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is successively washed with water and saturated salt solution, dried over anhydrous Na2SO4and concentrate. Received m Slany the residue purified by column chromatography to obtain 300 connection with the release of 76%.

1H NMR (DMSO-d6, 400 MHz): δ 10,802 (s, 1H), 9,491 (s, 1H), 7,990 (d, J=5.4 Hz, 1H), 7,495 (s, 1H), 7,295 (m, J=8.4 and 3.6 Hz, 4H), 7,236 (d, J=5.4 Hz, 1H), 7,133 (d, J=5.6 Hz, 1H), 6,486 (d, J=5.6 Hz, 1H), 5,902 (s, 1H), 2,402 (s, 3H); MS (m/e): 335,1 (M+1).

Examples 301-303: Synthesis of compounds 301-303

Connection 301-303 receive in a manner similar to that described in example 300.

ConnectionName1H NMR (CD3OD, 400 MHz)/MS
3012-methyl-N-(2-(4-phenoxyphenoxy)pyrimidine-4-yl)-1H-indol-5-amine
11,190 (s, 1H), 9,046 (s, 1H), 7,959 (s, 1H), 7,931 (d, J=6.0 Hz, 1H), 7,681 (d, J=7.2 Hz, 2H), 7,361 (t, J=8.0 to about 7.6 Hz, 2H), 7,114 (m, J=8.4 to 7.2 Hz, 3H), 6,903 (d, J=8.0 Hz, 2H), 6,755 (d, J=7.2 Hz, 2H), 6,179 (, 1H), 6,024 (s, 1H), 2,338 (s, 3H); MS (m/e): 409,2 (M+1)

302N2-cyclopropyl-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine
7,739 (d, J=6,4 Hz, 1H), 7,593 (s, 1H), 7,252 (d, J=7,6 Hz, 1H), 7,119 (d, J=8.0 Hz, 1H), 6,009 (s, 1H), 6,016 (d, J=6.0 Hz, 1H), 2,425 (s, 3H), 0,784 (m, J=5,2-2,4, 2H), 0,626 (m, J=2.0 to 0.8 Hz, 3H), 0,547 (m, J=2.0 to 1.2 Hz, 3H), MS (m/e): 280,2 (M+1)
303N2-cyclohexyl-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-d is Amin

Example 304: Synthesis of 5-(2-(3-methoxyphenoxy)pyrimidine-4-yloxy)-2-methyl-1H-indole (compound 304):

Connection 304

To a solution of 2,4-dichloropyrimidine (1 mmol) and 5-hydroxy-2-methylindole (1 mmol) in 5 ml EtOH add Et3N (1 mmol). The reaction mixture is heated under reflux for 5 hours. After removal of the solvent in vacuo and addition of H2O, the mixture is extracted with EtOAc. The organic layers are combined washed with saturated aqueous NaCl, dried over anhydrous Na2SO4and concentrated in vacuo. The obtained oily residue is purified by column chromatography to obtain 5-(2-chloropyrimidine-4-yloxy)-2-methyl-1H-indole with a yield of 75%.

5-(2-Chloropyrimidine-4-yloxy)-2-methyl-1H-indole (0.1 mmol) and m-methoxyphenol (0.1 mmol) dissolved in 0.5 ml of DMF. Then add K2CO3(0.2 mmol). After stirring the reaction mixture at 60°C for 5 hours, it is diluted with water and extracted with ethyl acetate. The organic layer is successively washed with water and saturated salt solution, dried over anhydrous Na2SO4and concentrate. The crude product is purified by column chromatography to obtain compound 304 with the output 76%.

1H NMR (CD3OD, 400 MHz): δ 8,303 (d, J=5.6 Hz, 1H, 8,084 (s, 1H), 7,305-UAH 7,262 (m, 3H), 6,908 (DD, J=8,8 Hz, J=2.4 Hz, 1H), 6,816-6,764 (m, 3H), 6,463 (d, J=5.6 Hz, 1H), 6,226 (s, 1H), 3,780 (s, 3H), 2,465 (s, 3H); MS (m/e): 346,5 (M-l).

Example 305: Synthesis of 3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzonitrile (compound 305)

Connection 305

To a solution of 2,4-dichloropyrimidine (1 mmol) and 5-aminobenzimidazole (1 mmol) in 5 ml of EtOH, add Et3N (1 mmol). The reaction mixture is heated under reflux for 5 hours. After removal of the solvent in vacuo and addition of H2O the mixture is extracted with EtOAc. The organic layers are combined washed with saturated aqueous NaCl, dried over anhydrous Na2SO4and concentrated in vacuo. The residue is purified by column chromatography to obtain N-(2-chloropyrimidine-4-yl)-1H-benzo[d]imidazol-5-amine to yield 80%.

N-(2-chloropyrimidine-4-yl)-1H-benzo[d]imidazol-5-amine (0.1 mmol), 3-aminobenzonitrile (0.1 mmol) and p-TsOH monohydrate (0.2 mmol) dissolved in 0.5 ml of DMF. After stirring the reaction mixture at 60°C for 5 hours, it is diluted with water and extracted with ethyl acetate. The organic layer is successively washed with water and saturated salt solution, dried over anhydrous Na2SO4and concentrate. The resulting oil purified by column chromatography to obtain compound 305 with the release of 76%.

1H NMR (CD3OD, 00 MHz): δ 8,178 (s, 1H), 7,942 (d, J=6,4 Hz, 2H), 7,825 (user., 1H), 7,633-7,603 (m, 2H), 7,469 (DD, J=8,8 Hz, 5 Hz, 1H), 7,212 (t, J=8,4 Hz, 1H), 7,075 (d, J=8.0 Hz, 1H), 6,254 (d, J=6.0 Hz, 1H), 3,345 (s, 1H); MS: 327,2 (M+1).

Example 306: Synthesis of N2-(3-methoxyphenyl)-N4-(2-methylbenzo[d]oxazol-6-yl)pyrimidine-2,4-diamine (compound 306)

Connection 306

To a solution of 2,4-dichloropyrimidine (1 mmol) and 2-methyl-1,3-benzoxazol-5-amine (1 mmol) in 5 ml EtOH add Et3N (1 mmol). The reaction mixture is heated under reflux for 5 hours. After removal of the solvent in vacuo and addition of H2O the mixture is extracted with EtOAc. The organic layers are combined washed with saturated aqueous NaCl, dried over anhydrous Na2SO4and concentrated in vacuo. The residue is purified by column chromatography to obtain N-(2-chloropyrimidine-4-yl)-2-methylbenzo[d]oxazol-6-amine with a yield of 73%.

N-(2-chloropyrimidine-4-yl)-2-methylbenzo[d]oxazol-6-amine (0.1 mmol), 3-methoxyaniline (0.1 mmol)and p-TsOH monohydrate (0.2 mmol) dissolved in 0.5 ml of DMF. After stirring the reaction mixture at 60°C for 5 hours, it is diluted with water and extracted with ethyl acetate. The organic layer is successively washed with water and saturated salt solution, dried over anhydrous Na2SO4and concentrate. The obtained oily residue is purified by column chromatography to obtain compounds the Oia 306 with the release of 82%.

1H NMR (DMSO-d6, 400 MHz): δ 9,431 (s, 1H), 9,158 (s, 1H), 8,136 (s, 1H), 8,022 (d, J=5.6 Hz, 1H), 7,566 (d, J=8,8 Hz, 1H), 7,517 (d, J=8,8 Hz, 1H), 7,418 (s, 1H), 7,367 (d, J=8.0 Hz, 1H), 7,126 (t, J=8,4 Hz, 1H), 6,490 (m, 1H), 6,224 (d, J=5,2 Hz, 1H), RUB 3.674 (s, 3H), to 2.609 (s, 3H); MS(m/e): 348,3 (M+1).

Example 307: Synthesis of N2-(3-ethynylphenyl)-N4-(2-methylbenzo[d]-oxazol-6-yl)pyrimidine-2,4-diamine (compound 307).

Connection 307 synthesized in a manner similar to that described in example 306.

1H NMR (DMSO-d6, 400 MHz): δ 9,566 (d, J=5,2 Hz, 1H), 9,309 (s, 1H), 8,099 (s, 1H), 8,038 (d, J=6.0 Hz, 1H), of 7.917 (s, 1H), 7,805 (d, J=8,4 Hz, 1H), 7,574 (m, 2H), 7,231 (m, 1H), 6,996 (d, J=7,6 Hz, 1H), 7,278 (d, J=5.6 Hz, 1H), 4,059 (s, 1H), 2,608 (s, 3H); MS (m/e): 342,2 (M+1).

Example 308: Synthesis of N2-(3-ethynylphenyl)-N4-(1H-indazol-6-yl)pyrimidine-2,4-diamine (compound 308)

Connection 308

To a solution of 2,4-dichloropyrimidine (1 mmol) and 5-aminoindazole (1 mmol)dissolved in 5 ml of EtOH, add Et3N (1 mmol). The reaction mixture is heated under reflux for 5 hours. After removal of the solvent in vacuo and addition of H2O, the mixture is extracted with EtOAc. The organic layers are combined washed with saturated aqueous NaCl, dried over anhydrous Na2SO4and concentrated in vacuo. The resulting oil purified by column chromatography to obtain N-(2-chloropyrimidine-4-yl)-1H-indazol-5-amine to yield 80%.

N-(2-chloropyrimidine-4-yl)-1H-indazol-5-the min (0.1 mmol), 3-ethylaniline (0.1 mmol)and p-TsOH (0.2 mmol, monohydrate) is dissolved in 0.5 ml of DMF. After stirring the reaction mixture at 60°C for 5 hours, it is diluted with water and extracted with ethyl acetate. The organic layer is successively washed with water and saturated salt solution, dried over anhydrous Na2SO4and concentrate. The residue is purified by column chromatography to obtain compound 308 with a yield of 74%.

1H NMR (DMSO-d6, 400 MHz): δ 12,966 (user. s, 1H), 9,344 (user. s, 1H), 9,234 (user. s, 1H), 8,145 (s, 1H), 8,005 (m, 2H), 7,893 (s, 1H), 7,795 (d, 1H), 7,527 (d, J=8,8 Hz, 1H), 7,471 (d, J=8,8 Hz, 1H), 7,212 (t, 1H), 7,021 (d, 1H), 6,626 (d, 1H), 4,037 (s, 1H); MS (m/e): 327,2 (M+1).

Example 309: Synthesis of N2-(3-methoxyphenyl)-N4-(2-methyl-1H-indol-5-yl) pyrimidine-2,4-diamine (compound 309)

Connection 309

2,4-Dichloro-5-ftorpirimidinu (1 mmol) and 5-amino-2-methylindol (1.5 mmol) dissolved in 3 ml of CH3OH and 9 ml of H2O. After stirring the reaction mixture at room temperature for 1 hour, it was diluted with H2O, acidified with 2n. HCl and treated with ultrasound. Then the reaction mixture is filtered, washed with H2O and dried to obtain N-(2-chloro-5-ftorpirimidinu-4-yl)-2-methyl-1H-indol-5-amine with a yield of 78%.

N-(2-chloro-5-ftorpirimidinu-4-yl)-2-methyl-1H-indol-5-amine (0.1 mmol), m-methoxyaniline (0.1 mmol), p-TsOH monohydrate (0.2 mmol) dissolved in 0.5 ml of DMF. After re is eshiwani the reaction mixture at 60°C for 5 hours, it is diluted with water and extracted with ethyl acetate. The organic layer is successively washed with water and saturated salt solution, dried over anhydrous Na2SO4and concentrate. The residue is purified by column chromatography to obtain compound 309 with the release of 60%.

1H NMR (CD3OD, 400 MHz, δ ppm): 7,854 (d, J=4.0 Hz, 1H), 7,703 (d, J=1,6, 1H), 7,248 (s, 2H), 7,177 (user, 2H), 7,054 (t, J=4,2 Hz, 2H), 6,942 (s, 2H), 3,506 (s, 3H), 2,235 (s, 3H); MS (m/e): 364,2 (M+1).

Example 310: Synthesis of 2-(3-methoxybenzylamine)-4-(2-methyl-1H-indol-5-ylamino)pyrimidine-5-carbonitrile (compound 310)

Connection 310

2-Methyl-2-pseudodomain (5 mmol) and atlatonementaustin (5 mmol) was dissolved in 20 ml EtOH. To it add K2CO3(10 mmol). After heating the mixture under reflux for 48 hours, it is cooled to room temperature and filtered. The solvent was concentrated in vacuo and purified by column chromatography to obtain 4-hydroxy-2-(methylthio)pyrimidine-5-carbonitrile with the release of 65%.

4-Hydroxy-2-(methylthio)pyrimidine-5-carbonitrile (3 mmol) and m-anisidine (3 mmol) in pentane-1-Ola heated under reflux for 40 hours under nitrogen atmosphere. The reaction mixture was concentrated in vacuo. The residue is washed with water and dried to obtain 4-hydroxy-2-(3-methoxybenzylamine)pyrimidine-5-carbonitrile.

To a solution of 4-hydroxy-2-(3-methoxybenzylamine)is eremein-5-carbonitrile in POCl 3add 0.5 ml of DMF. The solution is heated under reflux for 3 hours. The reaction mixture is cooled to room temperature and poured into ice water. The solution is brought to pH 8-9 with aqueous sodium carbonate and extracted with dichloromethane. The combined organic layers washed with saturated salt solution, dried over anhydrous Na2SO4concentrate in vacuo to obtain 4-chloro-2-(3-methoxybenzylamine)pyrimidine-5-carbonitrile.

4-Chloro-2-(3-methoxybenzylamine)pyrimidine-5-carbonitrile transform in connection 310 in a manner similar to that described in example 1.

1H NMR (DMSO-d6, 400 MHz): δ 10,925 (s, 1H), 9,710 (d, J=11.2 Hz, 1H), 9,349 (d, J=10.4 Hz, 1H), 8,441 (s, 1H), 7,474 (s, 1H), 7,252 (s, 1H), 7,223 (d, J=6,8 Hz, 1H), 7,187 (s, 1H), 7,062 (m, J=H)6,923 (d, J=2.0 Hz, 1H), 6,485 (t, 1H); 6,098 (s, 1H), 3,453 (s, 3H), 2,387 (s, 3H); MS (m/e): 371,2 (M+1).

Examples 311-317: Synthesis of compounds 311-317

Connection 311-317 receive in a manner similar to that described in example 310.

ConnectionName/structure1HNMR(DMSO-d6,400 Hz)/MS
3114-(2-methyl-1H-indol-5-ylamino)-2-(3-(3-morpholinopropan)
phenylamino)pyrimidine-5-carbonitrile
11,184 (s, 1H), 10,745 (s, 1H), 9,492 (s, 1H), 8,396 (s, 1H), 7,322 (s, 1H), 7,292 (d, J=7,2, 1H), 7,147 (m, 1H), 6,919 (m, 1H), 6,815 (d, J=8,8, 1H), 6,416 (d, J=7,2, 1H), 6,261 (t, J=4,8, 1H), 6,129 (s, 1H), 3,447 (m, 2H), 3,547 (m, 4H), 2,398 (s, 3H), 2,337 (m, 6H), 1,747 (m, 2H), MS (m/e): 484,2 (M+1)
3124-(2-methyl-1H-indol-5-yloxy)-2-(3-(3-
morpholinopropan)
phenylamino)pyrimidine-5-carbonitrile
MS (m/e): 485,3 (M+1)
3134-(2-methyl-1H-indol-5-ylamino)-2-(3-(2-morpholinoethoxy)
phenylamino)pyrimidine-5-carbonitrile
MS (m/e): equal to USD 470.5 (M+1)
3144-(4-fluoro-2-methyl-1H-indol-5-ylamino)-2-(3-
(trifluoromethyl)
phenylamino)pyrimidine-5-carbonitrile
MS (m/e): 427,2 (M+1)

3152-(3,4-dimethoxyphenylthio)-4-(2-methyl-1H-indol-5-ylamino)pyrimidine-5-carbonitrile
MS (m/e): 401,4 (M+1)
3164-(4-fluoro-2-methyl-1H-indol-5-ylamino)-2-(3-(2-morpholinoethoxy)
phenylamino)pyrimidine-5-carbonitrile
MS (m/e): 488,5 (M+1)
3172-(5-cyano-2-(3,4-
dimethoxyaniline)
pyrimidine-4-ylamino)benzamide
MS (m/e): to € 391.1 (M+1)

Example 318The analysis of the activity of KDR kinase using a set of Z'-lyte for analysis of kinase activity

Inhibition of kinase activity of recombinant catalytic domain of KDR (Invitrogen, Carlsbad, CA, U.S.A., Cat. PV3660) is determined using a set of Z'-LYTE™ Tyrl Peptide assay (Invitrogen, Cat. PV3190) in black 384-well the tablet (Thermolabsystems, Cambridge, U.K., Cat. the 7805). The analysis is carried out in accordance with the procedures recommended by the manufacturer.

Briefly, the analyzed compound (10 mm stock in DMSO) were diluted to 1:4 with distilled water containing 8% DMSO. The solution is placed in the hole for the study and in three control wells (C1, C2, and C3) the 2.5 µl/well. Coumarin-fluoresceine peptide substrate with doubly labelled mixed with the catalytic domain of KDR (kinase"). 5 μl of the mixture kinase/peptide added to each of the holes for research, C1 and C2, but not C3 (final concentration: 0.3 ág/ml kinase, 2 μm peptide). 5 μl of peptide Phosphor-Tyrl add in the hole C3. a 2.5 μl of 40 μm ATP solution add the hole for the research and the hole C2, and 2.5 μl of 1.33× kinase buffer (1× buffer: 50 mm HEPES, pH 7.5, 0.01% of Brij-35, 5 mm MgCl2, 5 mm MnCl2and 1 mm EGTA) added is in wells C1 and C3. The tablet briefly centrifuged at 1000 rpm for deposition only solution to the bottom of the hole, and then sealed and shaken at 250 rpm and 25°C for 1 hour.

Showing reagent diluted to 1:128 in accordance with the recommendation of the manufacturer. 5 µl of the diluted developing reagent is added to each well. Tablet centrifuged at 1000 rpm for deposition only solution to the bottom of the hole, and then sealed and shaken at 250 rpm and 25°C for 1 hour.

5 μl of stop reagent is added to each well. Tablet centrifuged at 1000 rpm for deposition only solution to the bottom of the hole, and then pressurized at 250 rpm and 25°C for 2 minutes. The emission of solution from each well was measured using reader with a microplate VictorTM3 at 400 nm excitation/emission445 nm and 520 nm. The ratio of the emission and the percentage of phosphorylation ("Phos.") calculated using the following equations:

where:

C100%= average signal emission of the coumarin 100% Phos. Control

C0%= average signal emission of the coumarin 0% Phos. Control

F100%= average signal emission of fluorescein 100% Phos. Control

F0%= average signal emission of fluorescein 0% Phos. Control

The ratio of inhibition is calculated as follows:

% Inhib the simulation = (Phos. in well C2 - Phos. in the test well)/(Phos. in well C2) × 100%

The result shows that all the compounds inhibit the activity of KDR. The values of the IC50are in the range of from 0.001 to 10 μm.

Other embodiments of

All the characteristics described in the present description, may be combined in any combination. Each feature described herein may be replaced with alternative sign, employees for the same, equivalent or similar purpose. Thus, unless explicitly approved otherwise, each of these signs is the only example of the total number of equivalent or similar features.

From the above description, the person skilled in the art can easily obtain the main characteristics of the present invention and may, without deviating from its spirit and scope, can make various changes and modifications of the present invention to adapt it to various uses and conditions. For example, compounds structurally similar to the compounds of the present invention, can be obtained and used to implement the present invention. Thus, other ways of implementation are also in the framework of the claims.

1. The compound of the following formula:

in which each of X and Y independently represents with the fight About, NR, where R represents H;
Z represents CR', where R' represents H or halogen;
V, U and T together are

or

each of R1, R2, R3, R4and R6independently represents H, halogen, cyano, C1-10alkyl;
R5represents a C1-10alkyl, optionally substituted by hydroxyl,6heterocyclization containing 1-2 N, and O atoms as heteroatoms;
With6aryl, optionally substituted hydroxy, halogen, cyano, C1-10the quinil,1-10alkylthio, halogen1-10the alkyl, O-phenyl, Halogens1-10alkylsulfonamides,1-10alkylaminocarbonyl,1-10alkylsulfonamides,1-10alkylsulfonate, O-C5-6heterocyclization containing 1 N, and O atoms as heteroatoms, optionally substituted C1-10alkylsulfonyl,1-10alkylsulfonyl; or
C1-10the alkyl may optionally substituted C1-10alkylaminocarbonyl,1-10alkoxycarbonyl,1-10alkylaminocarbonyl,1-10alkylsulfonyl, C1-10alkylsulfonamides,6heterocyclization containing as heteroatoms atoms N, O, which in turn may be substituted for hydroc the IC 1-10the alkyl, C1-10by alkyl, hydroxy-group, With1-10alkylsulfonyl,1-10alkoxycarbonyl; or
With1-10alkenyl may optionally substituted C1-10alkylaminocarbonyl; or
CARBONYLS1-10alkenyl may optionally substituted C6heterocyclization containing as heteroatoms atoms N, O; or
With1-10alkylaminocarbonyl may optionally substituted by hydroxy, C1-10alkoxy, C1-10alkylamino,1-10alkylaminocarbonyl,5-6heterocyclization containing as heteroatoms atoms N, O; or
With1-10alkylaminocarbonyl1-10the alkyl may optionally substituted C6heterocyclization containing as heteroatoms atoms N, O; or
aminocarbonyl1-10the alkyl may optionally substituted C3-6cycloalkyl, or
sulfonium may optionally substituted C6heterocyclization containing as heteroatoms atoms N, O; or
CARBONYLS1-10the alkyl may optionally substituted C6heterocyclization containing as heteroatoms atoms N, O; or
With1-10alkylsulfonyl may optionally substituted C1-10alkylamino,5-6heterocyclization containing as heteroatoms atoms N, O; or
1-10alkoxygroup may optionally substituted C1-10alkylamino, amino, C1-10alkoxy, hydroxy-group, With1-10alkylsulfonyl, C1-10alkylsulfonyl, C5-6heterocyclization containing the atoms O, N, S as heteroatoms, or a sulfur atom in the form of S(O)2or S(O), which may optionally substituted C1-10alkoxycarbonyl,1-10alkylsulfonyl;
With5-6heteroaryl containing as heteroatoms 1-2 N atom may be additionally substituted With1-10the alkoxyphenyl,1-10alkoxy, C1-10alkylsulfonamides, hydroxyphenyl,1-10alkylcarboxylic; or
With9heteroaryl containing as heteroatoms 1-2 atom N, O, possibly substituted C1-10by alkyl;
With3-6cycloalkyl,
R7represents a C1-10alkyl,
or its pharmaceutically acceptable salt.

2. The compound according to claim 1, in which X represents O or NH.

3. The compound according to claim 2, in which Y represents NH.

4. The compound according to claim 3, in which V, U and T together are

and Z represents CR', R' represents N.

5. The compound according to claim 4, in which R6represents N and R7represents methyl.

6. The compound according to claim 5, in which R5represents a C6aryl, it is certainly substituted with halogen, cyano, hydroxy, C1-10the quinil,5-6heterocyclization,1-10alkylthio;
or5-6heteroaryl, optionally substituted C1-10alkoxy;
or9heteroaryl, optionally substituted C1-10the alkyl.

7. The compound according to claim 1, where V, U and T together are

and Z represents CR', R' represents N.

8. The connection according to claim 7, in which R6represents N and R7represents methyl.

9. The compound according to claim 1, in which R5represents a C6aryl, optionally substituted with halogen, cyano, hydroxy, C1-10the quinil, C5-6heterocyclization,1-10alkylthio;
or5-C6heteroaryl, optionally substituted C1-10alkoxy;
or9heteroaryl, optionally substituted C1-10the alkyl.

10. The compound according to claim 1, in which Y represents NH.

11. The compound according to claim 1, in which the connection is one of the following connections:
N4-(2-methyl-1H-indol-5-yl)-N2-phenylpyrimidine-2,4-diamine;
N2-(3-ethynylphenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(3-bromophenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(3-forfinal)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(3-chlorophenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(Tr is permitil)phenyl)pyrimidine-2,4-diamine;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(methylsulphonyl)phenyl)pyrimidine-2,4-diamine;
N2-(3-methoxyphenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
ethyl 1-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)piperidine-4-carboxylate;
N2,N4-bis(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(1H-indazol-5-yl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(1H-benzo[d]imidazol-5-yl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(2-methoxyphenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(2-chlorophenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(2-bromophenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(4-forfinal)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
methyl 2-(4-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)acetate;
N4-(2-methyl-1H-indol-5-yl)-N2-(4-phenoxyphenyl)pyrimidine-2,4-diamine;
N2-(4-methoxyphenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N4-(2-methyl-1H-indol-5-yl)-N2-(4-(2-morpholinoethoxy)phenyl)pyrimidine-2,4-diamine;
N2-(3,4-differenl)-N2-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(3, 5dimethylphenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
2-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)ethanol;
N4-(2-methyl-1H-indol-5-yl)-N2-(2-morpholinoethyl)pyrimidine-2,4-diamine;
N-cyclopropyl-2-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)ndimethylacetamide;
N2-(3-(2-(dimethylamino)ethylsulfonyl)phenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-d is amine;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(1-(methylsulphonyl)piperidine-4-yloxy)phenyl)pyrimidine-2,4-diamine;
N-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)methanesulfonamide;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(2-morpholinoethoxy)phenyl)pyrimidine-2,4-diamine;
N2-(3-(3-(dimethylamino)propoxy)phenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
2-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethanol;
2-(2-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethanol;
N4-(2-methyl-1H-indol-5-yl)-N2-(2-(2-morpholinoethoxy)phenyl)pyrimidine-2,4-diamine;
N-methyl-3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzamide;
3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-(piperidine-1-yl)ethyl)benzamide;
N-(2-(dimethylamino)ethyl)-3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzamide;
N2-(3-(4-methoxyphenyl)-1H-pyrazole-5-yl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N-(3-ethynylphenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine;
N-(4-methoxyphenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine;
4-(2-methyl-1H-indol-5-yloxy)-N-(4-phenoxyphenyl)pyrimidine-2-amine;
N-(3-methoxyphenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(3-(thiomorpholine-1',1'-dioxide)propoxy)phenyl)pyrimidine-2-amine;
N-methyl-3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzamide;
trifter-N-(4-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)IU unsulfonated;
(S)-4-(2-methyl-1H-indol-5-yloxy)-N-(3-(pyrrolidin-3-yloxy)phenyl)pyrimidine-2-amine;
N-methyl-3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzosulfimide;
N-(4-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)methanesulfonamide;
2-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)-N-(2-morpholinoethyl)ndimethylacetamide;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(2-(methyl-sulfonyl)ethoxy)phenyl)pyrimidine-2-amine;
N-methyl(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)methanesulfonamide;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-forfinal)pyrimidine-2,4-diamine;
N2-(3-chlorophenyl)-N-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
2-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzonitrile;
N2-(3, 5dimethylphenyl)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(2-trifluoromethyl)phenyl)pyrimidine-2,4-diamine;
N2-(2-chlorophenyl)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(4-methoxyphenyl)pyrimidine-2,4-diamine;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(4-phenoxyphenyl)pyrimidine-2,4-diamine;
2-(1-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)piperidine-4-yl)ethanol;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(3-(methylsulphonyl)-propoxy)phenyl)pyrimidine-2,4-diamine;
2-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethanol;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(piperidine-3-and the hydroxy)phenyl)pyrimidine-2,4-diamine;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-((1-(methylsulphonyl)piperidine-4-yl)methoxy)phenyl)pyrimidine-2,4-diamine;
1-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)piperidine-4-ol;
4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(methylsulphonyl)phenyl)pyrimidine-2-amine;
N-cyclopropyl-2-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)ndimethylacetamide;
(E)-3-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)-N-methylacrylamide;
3-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)-N,N-dimethylpropanamide;
N-methyl-3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzamide;
N2-(2-forfinal)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzonitrile;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(methylthio)phenyl)pyrimidine-2,4-diamine;
N,N-dimethyl-3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzosulfimide;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(morpholinomethyl)phenyl)pyrimidine-2,4-diamine;
N2-(3,4-acid)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(4-chlorophenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(2,4-differenl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(3-chloro-2-forfinal)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(1H-indol-4-yl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(4-(3-(dimethylamino)propoxy)phenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
2(4-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethanol;
N2-(3-chloro-4-forfinal)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(benzo[d][1,3]-dioxol-5-yl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
(1-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)piperidine-4-yl)methanol;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(2-(4-(methylsulphonyl)piperazine-1-yl)ethoxy)phenyl)pyrimidine-2,4-diamine;
3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-propylbenzenesulfonyl;
N2-(2-chloro-4-forfinal)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
2-chloro-4-fluoro-5-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenol;
N2-(4-chloro-2-forfinal)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-(3-(2-(dimethylamino)ethoxy)phenyl)-N4-(2-methyl-1H-indol-5-yl)-pyrimidine-2,4-diamine;
N2-(2-methyl-1H-indol-5-yl)-N4-(3-(3-(methylsulphonyl)propoxy)phenyl)pyrimidine-2,4-diamine;
2-(1-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)piperidine-4-yl)ethanol;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(piperidine-4-ylethoxy)phenyl)pyrimidine-2,4-diamine;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(piperidine-3-yloxy)phenyl)pyrimidine-2,4-diamine;
1-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)piperidine-4-ol;
(S)-N4-(2-methyl-1H-indol-5-yl)-N2-(3-(pyrrolidin-3-yloxy)phenyl)pyrimidine-2,4-diamine;
(S)-N4-(2-methyl-1H-indol-5-yl)-N2-(3-(1-(methylsulphonyl)pyrrolidin-3-yloxy)phenyl)pyrimidine-2,4-diamine;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(piperidine-4-yloxy)phenyl)pyrimidine-2,4-diamine;
N4-(2-methyl-1H-shall ndol-5-yl)-N2-(3-(3-(4-(methylsulphonyl)piperazine-1-yl)-propoxy)phenyl)pyrimidine-2,4-diamine;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(3-morpholinoethoxy)phenyl)pyrimidine-2,4-diamine;
(R)-N4-(2-methyl-1H-indol-5-yl)-N2-(3-(1-(methylsulphonyl)pyrrolidin-3-yloxy)phenyl)pyrimidine-2,4-diamine;
(E)-N,N-dimethyl-3-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)acrylamide;
4-(4-fluoro-2-methyl-1H-indol-5-yl)-N-(3-(3-(thiomorpholine-1',1'-dioxide)propoxy)phenyl)pyrimidine-2-amine;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(2-(methylamino)ethoxy)phenyl)pyrimidine-2,4-diamine;
4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(3-(thiomorpholine-1'-oxide)propoxy)phenyl)pyrimidine-2-amine;
N-(2-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethyl)methanesulfonamide;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(3-thiomorpholine)phenyl)pyrimidine-2,4-diamine;
trifter-N-(4-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)methanesulfonamide;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(2-thiomorpholine)phenyl)pyrimidine-2,4-diamine;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(2-pyrrolidinone)phenyl)pyrimidine-2,4-diamine;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(2-morpholinoethyl)phenyl)pyrimidine-2,4-diamine;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(2-(pyrrolidin-1-yl)ethylsulfonyl)phenyl)pyrimidine-2,4-diamine;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-((4-(methylsulphonyl)piperazine-1-yl)methyl)phenyl)pyrimidine-2,4-diamine;
2-(4-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)piperazine-1-yl)ethanol;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(methylsulfonylmethyl)phenyl)p is rimidine-2,4-diamine;
N,N-dimethyl-3-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)propanamide;
(E)-N-methyl-3-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)acrylamide;
N4-(2-methyl-1H-indol-5-yl)-N2-(3-(tetrahydro-2H-Piran-4-yloxy)phenyl)pyrimidine-2,4-diamine;
N2-(3-(2-aminoethoxy)phenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)methanesulfonamide;
N-(2-hydroxyethyl)-3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzamide;
N-methyl-3-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)propanamide;
3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-(methylamino)-2-oxoethyl)benzamide;
3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-morpholinoethyl)benzamide;
3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-(piperidine-1-yl)ethyl)benzamide;
trifter-N-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)methanesulfonamide;
N-(2-methoxyethyl)-3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzamide;
N-(4-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)methanesulfonamide;
2-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)-N-(2-morpholinoethyl)ndimethylacetamide;
N2-(6-methoxypyridine-3-yl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
2-methyl-N-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-yl)-1H-indol-5-amine;
N-(3-(3-(dimethylamino)propoxy)phenyl)-4-(2-methyl-1H-indol-5-yloxy)PI is kidin-2-amine;
2-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenoxy)ethanol;
N-(3-(2-(dimethylamino)ethoxy)phenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine;
N-cyclopropyl-2-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)ndimethylacetamide;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(3-(methylsulphonyl)propoxy)phenyl)pyrimidine-2-amine;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(piperidine-4-ylethoxy)phenyl)pyrimidine-2-amine;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(piperidine-3-yloxy)phenyl)pyrimidine-2-amine;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(piperidine-4-yloxy)phenyl)pyrimidine-2-amine;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(1-(methylsulphonyl)piperidine-4-yloxy)phenyl)pyrimidine-2-amine;
1-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)piperidine-4-ol;
(1-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)piperidine-4-yl)methanol;
2-(1-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)piperidine-4-yl)ethanol;
N-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)methanesulfonamide;
(S)-4-(2-methyl-1H-indol-5-yloxy)-N-(3-(1-(methylsulphonyl)pyrrolidin-3-yloxy)phenyl)pyrimidine-2-amine;
(E)-N,N-dimethyl-3-(3-(4-(2-methyl-1H-indol-5-yloxy)-pyrimidine-2-ylamino)phenyl)acrylamide;
3-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)-1-morpholinopropan-1-he;
N-(3-(2-methoxyethoxy)phenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(morpholinomethyl)the dryer is l)pyrimidine-2-amine;
N-(2-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenoxy)ethyl)methanesulfonamide;
(R)-4-(2-methyl-1H-indol-5-yloxy)-N-(3-(1-(methylsulphonyl)pyrrolidin-3-yloxy)phenyl)pyrimidine-2-amine;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(2-morpholinoethoxy)phenyl)pyrimidine-2-amine;
N-(2-(dimethylamino)ethyl)-3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzamide;
N-(3-(2-methoxyethoxy)phenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(morpholinomethyl)phenyl)pyrimidine-2-amine;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(3-thiomorpholine)phenyl)pyrimidine-2-amine;
N-(3-(2-(dimethylamino)ethylsulfonyl)phenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(2-morpholinoethyl)phenyl)pyrimidine-2-amine;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(2-(pyrrolidin-1-yl)ethylsulfonyl)phenyl)pyrimidine-2-amine;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(2-thiomorpholine)phenyl)pyrimidine-2-amine;
4-(2-methyl-1 H-indol-5-yloxy)-N-(3-(2-(pyrrolidin-1-yl)ethoxy)phenyl)pyrimidine-2-amine;
4-(2-methyl-1 H-indol-5-yloxy)-N-(3 -((4-(methylsulphonyl)piperazine-1-yl)methyl)phenyl)pyrimidine-2-amine;
2-(4-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)piperazine-1-yl)ethanol;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-((tetrahydro-2H-Piran-4-yl)methoxy)phenyl)pyrimidine-2-amine;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(methylsulfonylmethyl)phenyl)pyrimidine-2-amine;
tert-butyl-(2-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenoxy)ethyl)piperazine-1-carboxylate;
N,N-dimethyl-3-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)propanamide;
(E)-N-methyl-3-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)acrylamide;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(tetrahydro-2H-Piran-4-yloxy)phenyl)pyrimidine-2-amine;
N-(3-(2-aminoethoxy)phenyl)-4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine;
N-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)methanesulfonamide;
N-(2-hydroxyethyl)-3-(4-(2-methyl-1H-indol-5-yloxy)-pyrimidine-2-ylamino)benzamide;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(2-(piperazine-1-yl)ethoxy)phenyl)pyrimidine-2-amine;
3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-(2-(methylamino)-2-oxoethyl)benzamide;
3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-(2-morpholinoethyl)benzamide;
3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-(2-(piperidine-1-yl)ethyl)benzamide;
N-methyl-3-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)propanamide;
N-(2-methoxyethyl)-3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzamide;
N-(4-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)methanesulfonamide;
2-(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)-N-(2-morpholinoethyl)ndimethylacetamide;
4-(2-methyl-1H-indol-5-yloxy)-N-(3-(2-methylsulphonyl)ethoxy)phenyl)pyrimidine-2-amine;
N-methyl(3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)methanesulfonamide;
N-(6-methoxypyridine-3-yl)-4-(2-methyl-1H-indol-5-yloxy)pyrimi the Jn-2-amine;
methyl 2-(4-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)acetate;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(2-methoxyphenyl)-pyrimidine-2,4-diamine;
N2-(3-bromophenyl)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(methylsulphonyl)phenyl)pyrimidine-2,4-diamine;
3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzonitrile;
N2-(2-chloro-4-forfinal)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)methanesulfonamide;
N2-(3,4-differenl)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(2-morpholino-ethoxy)phenyl)pyrimidine-2,4-diamine;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(2-(4-(methylsulphonyl)piperazine-1-yl)ethoxy)phenyl)pyrimidine-2,4-diamine;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(2-(2-morpholino-ethoxy)phenyl)pyrimidine-2,4-diamine;
N2-(3-(3-(dimethylamino)propoxy)phenyl)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N-cyclopropyl-2-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)ndimethylacetamide;
N-(2-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethyl)methanesulfonamide;
2-(2-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethanol;
N2-(3-(2-(dimethylamino)ethoxy)phenyl)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
(1-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-yl) - Rev. Mino)benzyl)piperidine-4-yl)methanol;
3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-methylbenzamide;
trifter-N-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)methanesulfonamide;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(piperidine-4-ylethoxy)phenyl)pyrimidine-2,4-diamine;
(E)-3-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)-1-morpholinopropan-2-EN-1-he;
trifter-N-(4-(4-(4-fluoro-2-methyl-1H-indol-5-amino)pyrimidine-2-ylamino)phenyl)methanesulfonamide;
N-(5-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)pyridine-2-yl)ndimethylacetamide;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(morpholinomethyl)phenyl)pyrimidine-2,4-diamine;
3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-methylbenzenesulfonamide;
N-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(2-methoxyethoxy)-phenyl)pyrimidine-2,4-diamine;
4-(4-fluoro-2-methyl-1H-indol-5-yl)-N-(3-(3-(thiomorpholine-1',1'-dioxide)propoxy)phenyl)pyrimidine-2-amine;
N-(2-(dimethylamino)ethyl)-3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzamide;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(2-(methylamino)-ethoxy)phenyl)pyrimidine-2,4-diamine;
(E)-3-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)-1-morpholinopropan-2-EN-1-he;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(3-thiomorpholine)phenyl)pyrimidine-2,4-diamine;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(2-morpholino-ethylsulfonyl)phenyl)pyrimidine-2,4-diamine;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(2-t is morpholino-ethoxy)phenyl)pyrimidine-2,4-diamine;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(2-(pyrrolidin-1-yl)ethoxy)phenyl)pyrimidine-2,4-diamine;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-((4-(methylsulphonyl)piperazine-1-yl)methyl)phenyl)pyrimidine-2,4-diamine;
2-(4-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)piperazine-1-yl)ethanol;
3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenylmethanesulfonyl;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(methylsulphonyl-methyl)phenyl)pyrimidine-2,4-diamine;
tert-butyl 4-(2-(3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethyl)piperazine-1-carboxylate;
tert-butyl 4-(2-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenoxy)ethyl)piperazine-1-carboxylate;
3-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)-N,N-dimethylpropanamide;
(E)-3-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)-N-methylacrylamide;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-((tetrahydro-2H-Piran-4-yl)methoxy)phenyl)pyrimidine-2,4-diamine;
N2-(3-(2-aminoethoxy)phenyl)-N4-(4-fluoro-2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)methanesulfonamide;
3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-hydroxyethyl)benzamide;
3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-morpholinoethyl)benzamide;
3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-(piperidine-1-yl)ethylbenzamide;
3-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)-N-methylpropanamide;
3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-methoxyethyl)benzamide;
N-(4-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)methanesulfonamide;
2-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenyl)-N-(2-morpholinoethyl)ndimethylacetamide;
3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-N-(2-(methylamino)-2-oxoethyl)benzamide;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(3-(tetrahydro-2H-Piran-4-yloxy)phenyl)pyrimidine-2,4-diamine;
1-(3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)benzyl)sulfonylmethane;
N4-(4-fluoro-2-methyl-1H-indol-5-yl)-N2-(6-methoxypyridine-3-yl)pyrimidine-2,4-diamine;
4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(2-morpholinoethoxy)phenyl)pyrimidine-2-amine;
4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(3-morpholinoethoxy)phenyl)pyrimidine-2-amine;
2-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenoxy)ethanol;
4-(4-fluoro-2-methyl-1 H-indol-5-yloxy)-N-(3-(3-(thiomorpholine-1',1'-dioxide)propoxy)phenyl)pyrimidine-2-amine;
(R)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(pyrrolidin-3-yloxy)phenyl)pyrimidine-2-amine;
(S)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(pyrrolidin-3-yloxy)phenyl)pyrimidine-2-amine;
4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(1-(methylsulphonyl)piperidine-4-yloxy)phenyl)pyrimidine-2-amine;
(R)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-3-(1-(methylsulphonyl)pyrrolidin-3-yloxy)phenyl)pyrimidine-2-amine;
N-(2-(dimethylamino)ethyl)-3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzamide;
(1-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)piperidine-4-yl)methanol;
2-(1-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)piperidine-4-yl)ethanol;
4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(2-(methylamino)ethoxy)phenyl)pyrimidine-2-amine;
(E)-3-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)-1-morpholinopropan-2-EN-1-he;
4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(morpholinomethyl)-phenyl)pyrimidine-2-amine;
(S)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(1-(methylsulphonyl)pyrrolidin-3-yloxy)phenyl)pyrimidine-2-amine;
3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-methylbenzamide;
N-(2-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenoxy)ethyl)methanesulfonamide;
trifter-N-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-Ilmenau)phenyl)methanesulfonamide;
4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(3-thiomorpholine)phenyl)pyrimidine-2-amine;
4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(2-(pyrrolidin-1-yl)ethylsulfonyl)phenyl)pyrimidine-2-amine;
4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(2-morpholinoethyl)phenyl)pyrimidine-2-amine;
4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(2-thiomorpholine)phenyl)pyrimidine-2-amine;
4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(2-(pyrrolidin-1-yl)ethoxy)phenyl)pyrimidine-2-amine;
4-(4-fluoro-2-methyl-1H-shall ndol-5-yloxy)-N-(3-((4-(methylsulphonyl)piperazine-1-yl)methyl)phenyl)pyrimidine-2-amine;
2-(4-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)piperazine-1-yl)ethanol;
4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-((tetrahydro-2H-Piran-4-yl)methoxy)phenyl)pyrimidine-2-amine;
trifter-N-(4-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)methanesulfonamide;
tert-butyl 4-(2-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenoxy)ethyl)piperazine-1-carboxylate;
4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(tetrahydro-2H-Piran-4-yloxy)phenyl)pyrimidine-2-amine;
N-(3-(2-aminoethoxy)phenyl)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-amine;
N-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)benzyl)methanesulfonamide;
3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-(2-hydroxyethyl)benzamide;
3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-(2-(methylamino)-2-oxoethyl)benzamide;
3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-(2-morpholinoethyl)benzamide;
N-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)methanesulfonamide;
3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-(2-(piperidine-1-yl)ethyl)benzamide;
3-(3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)-N-methylpropanamide;
3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)-N-(2-methoxyethyl)benzamide;
N-(4-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)methanesulfonamide;
2-(3-(4-(4-fluoro-2-meth is l-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenyl)-N-(2-morpholinoethyl)ndimethylacetamide;
4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(3-(2-(methylsulphonyl)ethoxy)phenyl)pyrimidine-2-amine;
4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-N-(6-methoxypyridine-3-yl)pyrimidine-2-amine;
3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenol;
4-(5-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-1H-pyrazole-3-yl)phenol;
2-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenol;
4-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenol;
4-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenol;
3-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)phenol;
2-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenol;
4-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenol;
3-(4-(4-fluoro-2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)phenol;
3-(4-(2-methylbenzo-[d]oxazol-6-ylamino)pyrimidine-2-ylamino)phenol;
3-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-pyrimidine-2-ylamino)phenol;
N-(2-methoxypyridine-4-yl)-N-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N-(2-methoxypyridine-4-yl)-N-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N-(5-(4-(2-methyl-1H-indol-5-yloxy)pyrimidine-2-ylamino)pyridine-2-yl)methanesulfonamide;
N-(2-(4-pertenece)pyrimidine-4-yl)-2-methyl-1H-indol-5-amine;
2-methyl-N-(2-(4-phenoxyphenoxy)pyrimidine-4-yl)-1H-indol-5-amine;
N2-cyclopropyl-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
N2-cyclohexyl-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
5-(2-(3-methoxyphenoxy)pyrimidine-yloxy)-2-methyl-1H-indole;
3-(4-(2-methyl-1H-indol-5-ylamino)pyrimidine-2-ylamino)-benzonitrile;
N2-(3-methoxyphenyl)-N4-(2-methylbenzo[d]oxazol-6-yl)pyrimidine-2,4-diamine;
N2-(3-ethynylphenyl)-N4-(2-methylbenzo[d]-oxazol-6-yl)pyrimidine-2,4-diamine;
N2-(3-ethynylphenyl)-N4-(1H-indazol-6-yl)pyrimidine-2,4-diamine;
N2-(3-methoxyphenyl)-N4-(2-methyl-1H-indol-5-yl)pyrimidine-2,4-diamine;
2-(3-methoxybenzylamine)-4-(2-methyl-1H-indol-5-ylamino)pyrimidine-5-carbonitrile;
4-(2-methyl-1H-indol-5-ylamino)-2-(3-(3-morpholinopropan)phenylamino)pyrimidine-5-carbonitrile;
4-(2-methyl-1H-indol-5-yloxy)-2-(3-(3-morpholinopropan)-phenylamino)pyrimidine-5-carbonitrile;
4-(2-methyl-1H-indol-5-ylamino)-2-(3-(2-morpholinoethoxy)phenylamino)pyrimidine-5-carbonitrile;
4-(4-fluoro-2-methyl-1H-indol-5-ylamino)-2-(3-(trifluoromethyl)phenylamino)pyrimidine-5-carbonitrile;
2-(3,4-dimethoxyphenylthio)-4-(2-methyl-1H-indol-5-ylamino)pyrimidine-5-carbonitrile;
4-(4-fluoro-2-methyl-1H-indol-5-ylamino)-2-(3-(2-morpholinoethoxy)phenylamino)pyrimidine-5-carbonitrile;
2-(5-cyano-2-(3,4-dimethoxyaniline)pyrimidine-4-ylamino)-benzamide.

12. The method of treatment is associated with angiogenesis disorder comprising administration to a subject in need, an effective amount of the compounds and/or its pharmaceutically acceptable salt according to claim 1.

13. The method according to item 12, where associated with angiogenesis disorder is a cancer or age-related macular degeneration./p>

14. A method of inhibiting the activity of the receptor domain insertions kinase, comprising the bringing into contact of the receptor with an effective amount of the compounds and/or its pharmaceutically acceptable salt according to claim 1.

15. Method of inhibiting angiogenesis comprising the administration to a subject in need, an effective amount of the compounds and/or its pharmaceutically acceptable salt according to claim 1.

16. A method of treating age-related macular degeneration, comprising introducing to a subject in need, an effective amount of the compounds and/or its pharmaceutically acceptable salt according to claim 1.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: in formula (1): R1 means haloalkyl containing 1-6 fluorine atoms; R2 means C1-C6alkyl or halogen; R3 means -L-NR4R5, -X-NR-C(O)R8 or -X-NR-C(O)NR4R5 wherein L means -X-C(O), -(CR2)j, -O(CR2)1-4 or and X means (CR2)j or [C(R)(CR2OR)]; R4 and R5 independently mean H, C1-C6alkyl, halogen-substituted C1-C6alkyl, hydroxy group-substituted C1-C6alkyl, or (CR2)k-R6; R8 independently means (CR2)k-R6 or C1-C6alkyl, or halogen-substituted C1-C6alkyl; R7 means H; alternatively, R4 and R5 together with N atom in each NR4 R5 form a 4-7-member heterocyclic ring containing 1 -2 heteroatoms independently specified in N and O substituted by 0-3 groups R11; R11 means R8, (CR2)k-OR7, CO2R7, (CR2)k-C(O)-(CR2)k-R8, (CR2)kC(O)NR7R7 or (CR2)kS(O)1-2R8; each R means H or C1-C6alkyl; each k is equal to 0-6; and j and m are independently equal to 0-4; provided R1 does not mean trifluoromethoxygroup, provided R3 means C(O)NH2, C(O)NR12R13; wherein R12 and R13 together form piperazinyl; the values of the radical R6 are presented in the patent claim. The invention also refers to the pharmaceutical composition containing said compounds.

EFFECT: producing new 5-(4-(halogenalkoxy)phenyl)pyrimidin-2-amine derivatives showing c-kit, PDGFRα, PDGFRβ kinase inhibitory activity, optionally in the form of isomers or pharmaceutically acceptable salts.

12 cl, 77 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention describes poly(ADP-riboso)polymerase inhibitors of formula (Ik) its pharmaceutically acceptable salt wherein R101, R104 and R105 represent H; R102 represents R11 wherein R11 is specified from pyrrolidinyl, oxazolyl, imidazolidinyl, isothiazolidinyl, piperidinyl, piperazinyl and azepanyl with R102 being substituted by one or two (O) substitutes; R103 represents fluorine, besides, a pharmaceutical composition on the basis of said compounds showing poly(ADP-riboso)polymerase (PARP) inhibitory activity, a method of treating cancer and a method of reducing tumour volume in a mammal.

EFFECT: there are produced and described new compounds which show poly(ADP-riboso)polymerase (PARP) inhibitory activity.

9 cl, 491 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula (II)

or to its pharmaceutically acceptable salt wherein the ring A represents a group presented by formula 2 R1 represents hydrogen or C1-6alkyl; R2 represents -SR5, halogen, halogenated C1-6alkyl, etc., R3 represents a group presented by formula: -CH=CH-C(RaRb)-Rc-Rd, or a group presented by formula: -(CReRf)m-C(RaRb)-Rc-Rd wherein radicals and symbols have the values presented in the patent claim, R4 represents -OR6, -CONR7R8, -NR9CONR7R8, -(CR10R11)POH, -(CR10R11)pOCONR7R8, -NR9COR12, -(CR10R11)pNR9COR12, -C(=O)NR9OR12, -CONR9CONR7R8, -CN, halogen or NR9(C=O)OR12; R5 represents C1-6alkyl; R6 represents -CONR7R8; each of R7 and R8 independently represents hydrogen or etc., R10 and R11 independently represents hydrogen; R12 represents C1-6alkyl; each of m and p independently represents an integer 1 to 3. This compound is applicable as a type 1 11β-hydroxysteroiddehydrogenase inhibitor.

EFFECT: invention also refers to single compounds, pharmaceutical compositions on the basis of the declared compounds, to a method for preventing and treating diabetes and the use of the compound of formula (II).

21 cl, 289 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new piperazine amide derivatives of formula wherein X represents N or CH; Y represents N or CH; R1 represents lower alkyl, phenyl, phenyl-lower alkyl wherein phenyl can be optionally substituted by 1-2 substitutes independently specified in a group consisting of halogen, lower alkyl; R2 represents lower alkyl, phenyl, naphthyl or heteroaryl specified in dimethylisoxazolyl, quinolinyl, thiophenyl or pyridinyl wherein phenyl or heteroaryl are optionally substituted by 1 substitute optionally specified in a group consisting of halogen, lower alkoxy group, fluor-lower alkyl, lower alkoxy-carbonyl and phenyl; R3 represents phenyl, pyridinyl or pyrazinyl wherein phenyl, pyridinyl or pyrazinyl are substituted by 1-2 substituted optionally specified in a group consisting of halogen, lower alkyl and fluor-lower alkyl; R4, R5, R6, R7, R8, R9, R10 and R11 independently represent hydrogen, as well as to their physiologically acceptable salts. These compounds are bound with LXR alpha and LXR beta, and are applicable as therapeutic agents for treatment and/or prevention of high lipid levels, high cholesterol levels, low HDL cholesterol, high LDL cholesterol, atherosclerotic diseases, diabetes, non insulin dependent diabetes mellitus, metabolic syndrome, dislipidemia, sepsis, inflammatory diseases, infectious diseases, skin diseases, colitis, pancreatitis, cholestasis, liver fibrosis, psoriasis, Alzheimer's disease, etc.

EFFECT: preparing new piperazine amide derivatives.

15 cl, 88 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to quinoline derivatives of formula I

, or to its pharmaceutically acceptable salts, wherein X1 represents O; p represents 0, 1 or 2; each group R1 which can be identical or different and which can be located only in positions of 6- and/or 7-quinoline ring, specified in halogen, cyano, carboxy, (1-6C)alkoxycarbonyl, carbamoyl, (1-6C)alkoxy, N-(1-6C)alkylcarbamoyl, N,N-di-[(1-6C)alkyl]carbamoyl, or in a group of formula: Q1-X2-, wherein X2 represents CO and Q1 represents pyrrolidine, q represents 0 or 1; R2 represents (1-6C)alkoxy; R3 represents hydrogen or (1-6C)alkyl; R4 represents hydrogen; R5 represents hydrogen, methyl, ethyl, propyl, allyl, 2-propynyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3-fluoropropyl, 3,3-difluoropropyl, 3,3,3-trifluoropropyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, 3-methoxypropyl, cyanomethyl, 2-cyanoethyl or 3-cyanopropyl; the ring A represents a 5-membor monocyclic heteroaryl ring with up to three ring heteroatoms specified in oxygen, nitrogen and sulphur; r represents 0, 1 or 2; and each group R6 which can be identical or different is specified in amino, (1-6C)alkyl, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, or in a group of formula: -X6-R15 wherein X6 represents a single link and R15 represents (1-6C)alkoxy-(1-6C)alkyl, di-[(1-6C)alkyl]amino-(1-6C)alkyl or in a group of formula: -X7-Q3 wherein X7 represents C(R17)2N(R17) wherein each R17 represents hydrogen and Q3 represents (3-8C)cycloalkyl, and wherein any CH2 group within the R6 group optionally carries a hydroxy group on each said group. Also, the invention refers to methods for making the compound of formula I, to a pharmaceutical composition on the basis of the compound of formula I, to applying the compound of formula I and the combinations on the basis of the compound of formula I and additional anticancer drugs.

EFFECT: there are produced new quinoline derivatives effective in treating diabetic retinopathy and disturbed cell proliferation.

15 cl, 6 tbl, 32 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing piperazinophenols, involving reaction of piperazine, N-(β-aminoethyl)piperazine, N-(β-benzylaminoethyl)piperazine or N,N1-bis-(piperazinoethyl)ethylenediamine with a Mannich base in an aqueous medium at temperature 90-110°C in molar ratio of piperazine, N-(β-aminoethyl)piperazine, N-(β-benzylaminoethyl)piperzine:Mannich base equal to 1:0,8-2, N,N1-bis-(piperazinoethyl)ethylenediamine:Mannich base equal to 1:2 or 1:4 until release of dimethylamine stops; as well as aminomethylation of piperazine or N-(β-aminoethyl) piperazine with diphenylol propane (DPP) in the presence of formaldehyde (FA) in an aqueous medium with molar ratio piperazine: FA: DPP equal to 1:1:1 or 1:2:2 at temperature 50-90°C for 4-10 hours. Reactants react in the presence of a surfactant in amount of 2-6% of the weight of the starting piperazine, and the surfactant used is neonol, OP-7, OP-10.

EFFECT: ensuring fire safety of the process, high output of the end product which can be used as antioxidant phenol stabilisers.

1 cl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula 1c

, where A, B, R1, R2 and n have values given in the description, and pharmaceutically acceptable salts thereof. The invention also relates to pharmaceutical compositions based on compounds of formula 1c, which are used as modulators of ATP-binding cassette ("ABC") transporters or fragments thereof, including cystic fibrosis transmembrane conductance regulator ("CFTR"). The present invention also relates to a method of modulating ABC-transporter activity and methods of treating ABC-transporter mediated diseases using compounds of formula 1c.

EFFECT: improved method.

32 cl, 3 tbl, 118 ex

FIELD: chemistry.

SUBSTANCE: invention relates to use of 1,2,4-triazole derivatives of formula I:

, where R1, R2 and R3 independently denote hydrogen or halogen; R4 denotes C1-C6 alkyl; R5 and R6 independently denote C1-C6 alkyl or, together with a nitrogen atom to which they are bonded, form a 5-7-member heterocyclyl group, in which the 6-member heterocyclyl can further contain one oxygen or nitrogen atom and can be substituted with acetyl, C1-C6 alkyl or phyenyl; X-S-, -SO-, -SO2- or O; and n is a whole number selected from 1-8; or pharmaceutically acceptable salts, stereoisomers or solvates thereof, when producing a drug for treating or preventing sigma-1 receptor-mediated diseases or conditions, methods of producing said compounds, intermediate compounds and pharmaceutical compositions which contain compounds of formula 1.

EFFECT: improved compounds.

19 cl, 49 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed compound relates to novel biaryl-meta-pyrimidine, corresponding to structure (A) and their pharmaceutically acceptable salts. In structure (A): X is selected from group consisting of bond O, and CH2, and Y represents bond; or X and Y together can represent bond; each R1 and R2 independent on each other are selected from group consisting of H and unsubstituted C1-C6alkyl; each of p, q, r, n, m independent on each other represents integer number 0 or 1; G0 is selected from group consisting from N and CH; each G represents independently CH, N, CR6 or C, when bound with X, on condition that not more than two groups of G represent N, and each R6 does not depend on another R6; R5 represents methyl, Values of other radicals are given in the invention formula.

EFFECT: compounds possess inhibiting activity with respect to family of JAK kinases, in particular JAK2 kinases, and can be used in treatment of myeloproliferative disease, which results from genetic or protein fusions, as a result of increase of function of kinase from family of JAK kinases in cell signal transmission, as well as in treatment of true polycythemia, primary thrombocytopenia, myeloid fibrosis with myeloid metaplasia, proliferative diabetic retinopathy, cancer or eye diseases.

66 cl, 2 tbl, 246 ex

FIELD: chemistry.

SUBSTANCE: invention relates to specific derivatives of bicyclic amides disclosed in the claim, as well as a pharmaceutical composition.

EFFECT: compounds having protein kinase inhibiting activity, meant for use in treating protein kinase-dependant diseases, preferably proliferative diseases such as tumorous diseases.

13 cl, 115 ex

FIELD: chemistry.

SUBSTANCE: compounds of formula (1) are described, where substitutes are as defined in the formula of invention. Methods of obtaining formula (1) compounds are described, when n equals 0. Described also is a fungicide composition based on formula (1) compounds and a phytopathogenic fungus control method which uses compounds in paragraph 1 or a composition based on the said compounds.

EFFECT: obtaining compounds with fungicide properties.

17 cl, 60 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: carboxylic acid compounds are presented by formula (I) where R1 represents (1) hydrogen atom, (2) C1-4alkyl; E represents -CO-; R2 represents (1) halogen atom, (2) C1-6 alkyl, (3) trihalogen methyl; R3 represents (1) halogen atom, (2) C1-6alkyl; R4 represents (1) hydrogen atom; R5 represents (1) C1-6alkyl; represents phenyl; G represents (1) C1-6alkylene; represents 9-12-merous bicyclic heterocycle containing heteroatoms, chosen of 1-4 nitrogen atoms, one or two oxygen atoms; m represents 0 or an integer 1 to 4, n represents 0 or an integer 1 to 4, and i represents 0 or an integer 1 to 11 where R2 can be identical or different provided m is equal to 2 or more, R3 can be identical or different provided n is equal to 2 or more, and R5 can be identical or different provided i is equal to 2 or more; both R12 and R13, independently represent (1) C1-4alkyl, (2) halogen atom, (3) hydroxyl or (4) hydrogen atom, or R12 and R13 together represent (1) oxo or (2) C2-5alkylene and where provided R12 and R13 simultaneously represent hydrogen atom, carboxylic acid compound presented by formula (I), represents a compound chosen from the group including the compounds (1) - (32), listed in cl.1 of the patent claim. Besides the invention concerns a pharmaceutical composition based in the compound of formula I and to application of the compound of formula I for making the pharmaceutical composition.

EFFECT: there are produced new carboxylic acid derivatives with antagonistic activity with respect to DP receptor.

14 cl, 74 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel soluble pharmaceutical salts formed from salt-forming active compound of the general formula (I) or (II) and sugar substitute that can be used in preparing medicinal agents useful in pain and enuresis treatment. Salt-forming active substance represents a salt-forming compound among 1-phenyl-3-dimethylaminopropane compounds of the general formula (I) wherein X means -OH, F, Cl, H or group -OCOR6; R1 represents (C1-C4)-alkyl group; R2 represents H or (C1-C4)-alkyl group; R3 represents H or (C1-C4)-alkyl group with a direct chain, or R2 and R3 form in common (C4-C7)-cycloalkyl group and if R5 means H then R4 represents group O-Z in meta-position wherein Z means H,(C1-C3)-alkyl, -PO-(O-C1-C4-alkyl)2, -CO-(O-C1-C5-alkyl), -CONH-C6H4-(C1-C3-alkyl), -CO-C6H4-R7 wherein R7 represents -OCO-C1-C3-alkyl in ortho-position or group -CH2N(R8)2 in meta- or para-position and wherein R8 means (C1-C4)-alkyl or 4-morpholino-group, either R4 represents S-(C1-C3)-alkyl in meta-position, meta-Cl, meta-F, group -CR9R10R11 in meta-position wherein R9, R10 and R11 mean H or F, group -OH in ortho-position, O-(C2-C3)-alkyl in ortho-position, para-F or group -CR9R10R11 in para-position wherein R9, R10 and R11 mean H or F, or if R5 means Cl, F, group -OH or O-C1-C3-alkyl in para-position then R4 means Cl, F, group -OH or O-(C1-C3)-alkyl in meta-position, or R4 and R5 form in common group 3,4-OCH=CH- or OCH=CHO-; R6 means (C1-C3)-alkyl, or salt-forming active substance represents a salt-forming compound among 6-dimethylaminomethyl-1-phenylcyclohexane compounds of the general formula (II) wherein R1' represents H, -OH, Cl or F; R2' and R3' have similar or different values and represent H, (C1-C4)-alkyl, benzyl, -CF3, -OH, -OCH2-C6H5, O-(C1-C4)-alkyl, Cl or F under condition that at least one among radicals R2' either R3' means H; R4' represents H, -CH3, -PO-(O-C1-C4-alkyl)2, -CO-(O-C1-C5-alkyl, -CO-NH-C6H4-(C1-C3)-alkyl, -CO-C6H4-R5', CO-(C1-C5)-alkyl), -CO-CHR6'-NHR7' or unsubstituted either substituted pyridyl, thienyl, thiazolyl or phenyl group; R5' represents -OC(O)-(C1-C3)-alkyl in ortho-position or -CH2N(R8')2 in meta- or para-position and wherein R8' means (C1-C4)-alkyl, or both radicals R8' in common with nitrogen atom (N) form 4-morpholino-group, and R6' and R7' have similar or different values and represent H or (C1-C6)-alkyl under condition that if both radicals R2' and R3' represent H then R4' doesn't mean -CH3 when R1' represents additionally H, -OH or Cl, either R4' doesn't mean H when R1' represents additionally -OH. Also, invention relates to a medicinal agent based on indicated salts.

EFFECT: valuable medicinal properties of salts and drug.

14 cl, 1 tbl, 8 ex

Novel benzodioxols // 2304580

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of benzodioxol of the formula (I): wherein R1, R2, R3, R4, R5, R6, R7 and X are given in the description and the invention claim, and to their pharmaceutically acceptable salts. Also, invention relates to pharmaceutical compositions based on compounds of the formula (I) and their using for preparing medicinal agents used in treatment and/or prophylaxis of diseases associated with modulation of CB1 receptors.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

19 cl, 279 ex

The invention relates to compounds of General formula I

including their optical isomers and mixtures of such isomers, where r1denotes hydrogen, C1-C6alkyl, C3-C6cycloalkyl or aryl, optionally substituted by 1-3 halogen atoms, R2and R3each independently of one another denote hydrogen or C1-C6alkyl, R4stands WITH1-C6alkyl or C3-C6quinil, R5, R6, R7and r8each denotes hydrogen and

,

r10denotes aryl, optionally substituted by 1-3 substituents selected from the group comprising halogen, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl,1-WITH4haloalkoxy,1-C4alkoxy, C1-C4alkyl, C1-C6alkylthio,3-C6alkyloxy, nitro and C1-C6alkoxycarbonyl or optionally substituted heteroaryl representing aromatic kolicevo the t hydrogen, WITH1-C6alkyl or C3-C6quinil, R12denotes hydrogen or C1-C6alkyl, Z represents hydrogen,- CO-R16or-CO-COOR16and R16stands WITH1-C6alkyl, -CH2-CO - C1-C6alkyl or phenyl

FIELD: chemistry.

SUBSTANCE: described is a method of producing L-gluconic acid and salt thereof, which involves treatment of aqueous solution of 6-bromo-6-deoxy-2,3-anhydro-D-manno-1,4-lactone with a base at pH equal to at least 12 and temperature from 45 to 60°C to obtain aqueous solution of L-gluconic acid. The invention also describes methods of producing 6-bromo-6-deoxy-2,3-anhydro-D-manno-1,4-lactone by reacting 2,6-dibromo-2,6-dideoxy-D-mannono-1,4-lactone with a Lewis base in a ketone solvent in the presence of catalytic amounts of water.

EFFECT: methods have high output and are realised with less expenses and without anhydrous solvents.

11 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel C-phenyl glycitol compound which serves as a preventive or therapeutic agent for sugar diabetes by inhibiting SGLT1 activity, as well as SGLT2 activity; demonstrating inhibiting effect on glucose absorption, and also acts on release of glucose with urine. The C-phenyl glycitol compound has formula (I) given below, or pharmaceutically acceptable salt or hydrate thereof, where R1 and R2 are identical or different and denote a hydrogen atom, a hydroxyl group, a C1-6 alkyl group, a C1-6 alkoxy group or a halogen atom, R3 is a hydrogen atom, a C1-6 alkyl group or a C1-6 alkoxy group, Y is a C1-6 alkylene group, -O-(CH2)n- (n is a whole number which assumes values from 1 to 4), provided that when Z denotes -NHC(= NH)NH2 or -NHCON(RB)Rc, n not equal to 1, Z is -CONHRA, -NHC(=NH)NH2 or -NHCON(RB)Rc, or The invention also relates to a pharmaceutical composition based on compounds of formula I.

EFFECT: high efficiency of the compounds.

19 cl, 8 tbl

FIELD: organic chemistry, medicine, endocrinology.

SUBSTANCE: invention relates to novel compounds representing C-glycoside derivatives and their salts of the formula: wherein ring A represents (1) benzene ring; (2) five- or six-membered monocyclic heteroaryl ring comprising 1, 2 or 4 heteroatoms chosen from nitrogen (N) and sulfur (S) atoms but with exception of tetrazoles, or (3) unsaturated nine-membered bicyclic heterocycle comprising 1 heteroatom representing oxygen atom (O); ring B represents (1) unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (2) saturated or unsaturated five- or six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (3) unsaturated nine-membered bicyclic carbocycle, or (4) benzene ring; X represents a bond or lower alkylene wherein values for ring A, ring B and X correlate so manner that (1) when ring A represents benzene ring then ring B is not benzene ring, or (2) when ring A represents benzene ring and ring B represents unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O and comprising benzene ring or unsaturated nine-membered bicyclic carbocycle comprising benzene ring then X is bound to ring B in moiety distinct from benzene ring comprised in ring B; each among R1-R4 represents separately hydrogen atom, -C(=O)-lower alkyl or lower alkylene-aryl; each R5-R11 represents separately hydrogen atom, lower alkyl, halogen atom, -OH, =O, -NH2, halogen-substituted lower alkyl-sulfonyl, phenyl, saturated six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N and O, lower alkylene-OH, lower alkyl, -COOH, -CN, -C(=O)-O-lower alkyl, -O-lower alkyl, -O-cycloalkyl, -O-lower alkylene-OH, -O-lower alkylene-O-lower alkyl, -O-lower alkylene-COOH, -O-lower alkylene-C(=O)-O-lower alkyl, -O-lower alkylene-C(=O)-NH2, -O-lower alkylene-C(=O)-N-(lower alkyl)2, -O-lower alkylene-CH(OH)-CH2(OH), -O-lower alkylene-NH, -O-lower alkylene-NH-lower alkyl, -O-lower alkylene-N-(lower alkyl)2, -O-lower alkylene-NH-C(=O)-lower alkyl, -NH-lower alkyl, -N-(lower alkyl)2, -NH-lower alkylene-OH or NH-C(=O)-lower alkyl. Indicated derivatives can be used as inhibitor of co-transporter of Na+-glucose and especially as a therapeutic and/or prophylactic agent in diabetes mellitus, such as insulin-dependent diabetes mellitus (diabetes mellitus 1 type) and non-insulin-dependent diabetes mellitus (diabetes mellitus 2 type), and in diseases associated with diabetes mellitus, such as insulin-resistant diseases and obesity.

EFFECT: valuable medicinal properties of compounds.

11 cl, 41 tbl, 243 ex

The invention relates to novel di - and trivalent small selectin inhibitors of formula II, where X is selected from the group comprising-CN, -(CH2)nCO2H, -(CH2)nCONHOH, -O(CH2)m-CO2H, -(CH2)nCOZ, -(CH2)nZ, -CH(CO2H), (CH2)mCO2H,

-OH; Y = -(CH2)f; R1, R2independently selected from the group including hydrogen, lower alkyl, halogen, -OZ, -NO2, -NH2; R3selected from the group including hydrogen, lower alkyl, hydroxy-lower alkyl, amino-lower alkyl, lower alkyl-carboxylic acid; f = 1 - 6; n = 0 to 2; b = 0 - 2; m = 1 to 3; Z represents lower alkyl, phenyl, or their pharmaceutically acceptable salts, esters, Amida
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