Compounds and compositions as protein kinase inhibitors

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I), specifically compounds of formula (Ia) which have inhibiting activity during activity of kinase selected from Abl, BCR-AbI, PDGF-R, trkB, c-SRC, BMX, FGFR3, b-RAF, SGK, Tie2, Lck, JNK2a2, MKK4, c-RAF, MKK6, SAPK2a and SAPK2P and pharmaceutical compositions containing such compounds. In the compound of formula I, Ia, m and n are equal to 0; R1 denotes XNR5R6, where X denotes a bond; R5 is selected from hydrogen, C1-6alkyl, phenyl, C5-10heteroaryl-C0-4alkyl, C3-6cycloalkyl and C3-10heterocycloalkyl-C0-4alkyl, where the heteroaryl and heterocycloalkyl contain 1-2 heteroatoms selected from nitrogen and oxygen; and R6 is selected from hydrogen and C1-6alkyl; or R5 and R6 together with the nitrogen atom with which both are bonded form a heteroaryl or heterocycloalkyl; where any of phenyl, heteroaryl, cycloalkyl and heterocycloalkyl, R5 or a combination of R5 and R6 can be optionally substituted with 1-3 radicals independently selected from a halogen group, C1-6alkyl, C1-6alkoxy group, halogen-substituted alkyl, -XNR7R8, -XOR7, -XR8, -XC(O)NR7R8, -XC(O)NR7XNR7R8, -XNR7C(O)R8, -XR9; where X denotes a bond or C1-4alkylene; R7 and R8 are independently selected from a group consisting of hydrogen and C1-4alkyl;and R8 is selected form C5-6heterocycloalkyl and C5-6heteroaryl; where said heterocycloalkyl or heteroaryl contain 1-2 heteroatoms selected from nitrogen and oxygen, and said heterocycloalkyl or heteroaryl in R8 is optionally substituted with a radical selected from a group consisting of C1-4alkyl and XOR7; R3 denotes -NR10R11; where R10 denotes hydrogen; R11 denotes phenyl; where phenyl in R11 is optionally substituted with 1-3 radicals selected from a halogen group, C1-6alkyl, C1-6alkoxy group, halogen-substituted alkyl, halogen-substituted alkoxy group, -NR12C(O)R13, -NR12C(O)NR12R13 and -NR12S(O)0-2R13; where R12 denotes hydrogen; R13 is selected from phenyl, C5-6heteroaryl and C5-6heterocycloalkyl; where any of phenyl, heteroaryl, cycloalkyl or heterocycloalkyl contains 1-2 heteroatoms selected from nitrogen and oxygen, and said heterocycloalkyl or heteroaryl in R13 is substituted with 1-3 radicals independently selected from a halogen group, C1-6alkyl, halogen-substituted C1-6alkyl, C1-6alkoxy group, halogen-substituted C1-6alkoxy group, -XNR7R8, phenyl-C0-4alkyl, C5-6heteroaryl-C0-4alkyl, C5-6heterocycloalkyl-C0-4alkoxy group and C5-6heterocycloalkyl-C0-4alkyl; where X, R7 and R8 are described above, and where any of the phenyl, heteroaryl or heterocycloalkyl fragments contain 1-2 heteroatoms selected from nitrogen and oxygen, and said heterocycloalkyl or heteroaryl in R13 optionally further substituted with 1-3 radicals independently selected from a halogen group, C1-6alkyl, halogen-substituted C1-6alkyl, hydroxy-substituted C1-6alkyl, C1-6alkoxy group; R15 and R16 are selected from phenyl substitutes given in values of R11 and R12 for formula I compounds.

EFFECT: compounds can be used to treat or prevent such diseases as proliferative disorders, and diseases resulting from anomalous activation of the immune and nervous systems.

8 cl, 1 tbl, 1 dwg, 1 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

where m and n denote 0;
R1means-XNR5R6where X designates the connection;
R5selected from hydrogen, C1-6of alkyl, phenyl, C5-10heteroaryl-C0-4of alkyl, C3-6cycloalkyl and C3-10heteroseksualci-C0-4of alkyl, where heteroaryl and heteroseksualci contain 1-2 heteroatoms selected from nitrogen and oxygen; and R6selected from hydrogen and C1-6of alkyl;
or R5and R6together with the nitrogen atom to which R5and R6both attached, form heteroaryl or heteroseksualci;
where any phenyl, heteroaryl, cycloalkyl and heteroseksualci R5or the combination of R5and R6may be optionally substituted by 1 to 3 radicals independently selected from halogroup,1-6of alkyl, C1-6alkoxygroup, galodamadruga of alkyl, -XNR7R8, -XOR7, -XR8, -XC(O)NR7R8, -XC(O)NR7XNR7R8, -XNR7C(O)R8, -XR9; where X denotes a bond or
With1-4alkylen;
R7and R8independently selected from the group consisting of hydrogen and C 1-4of alkyl; and R9choose from C5-6geterotsiklicheskie and C5-6heteroaryl; where these heteroseksualci or heteroaryl contain 1-2 heteroatoms selected from nitrogen and oxygen, and named heteroseksualci or heteroaryl R9optionally substituted radical selected from the group consisting of C1-4the alkyl and-XOR7;
R3refers to-NR10R11; where R10denotes hydrogen; R11denotes phenyl; where the phenyl, R11optionally substituted from 1 to 3 radicals selected from halogroup,1-6of alkyl, C1-6alkoxygroup, galodamadruga of alkyl, galataraseray alkoxygroup, -NR12C(O)R13, -NR12C(O)NR12R13and-NR12S(O)0-2R13; where R12denotes hydrogen; R13selected from phenyl,5-6heteroaryl and C5-6geterotsiklicheskie; where any phenyl, heteroaryl, cycloalkyl or heteroseksualci contain 1-2 heteroatoms selected from nitrogen and oxygen, and named heteroseksualci or heteroaryl R13optionally substituted from 1 to 3 radicals independently selected from halogroup, C1-6of alkyl, galodamadruga C1-6of alkyl, C1-6alkoxygroup, galataraseray1-6alkoxygroup, -XNR7R8, phenyl-C0-4of alkyl, C5-6heteroaryl-C0-4of alkyl, C5-6heterocy loukil-C 0-4alkoxygroup and C5-6heteroseksualci-C0-4of alkyl; where X, R7and R8described above, and where any phenyl, heteroaryl or heterologously fragment contain 1-2 heteroatoms selected from nitrogen and oxygen, and named heteroseksualci or heteroaryl R13optional optionally substituted from 1 to 3 radicals independently selected from halogroup,1-6of alkyl, galodamadruga1-6of alkyl, replacement With1-6of alkyl, C1-6alkoxygroup,5-6geterotsiklicheskie and galataraseray1-6alkoxygroup;
and its pharmaceutically acceptable salts.

2. The compound of formula Ia

where n is selected from 0,1, 2 and 3;
q is chosen from 0 and 1;
R5selected from hydrogen, C1-6of alkyl, phenyl, C5-10heteroaryl-C0-4of alkyl, C3-6cycloalkyl and C3-10heteroseksualci-C0-4of alkyl, where heteroaryl and heteroseksualci contain 1-2 heteroatoms selected from nitrogen and oxygen; and R6selected from hydrogen and C1-6of alkyl;
or R5and R6together with the nitrogen atom to which R5and R6both attached, form heteroaryl or heteroseksualci;
where any phenyl, heteroaryl, cycloalkyl and heteroseksualci R5or the combination of R5and R6may be optionally substituted on the 1 to 3 radicals, independently selected from halogroup,1-6of alkyl, C1-6alkoxygroup, galodamadruga of alkyl, carbonyl group, -XNR7R8, -XOR7, -XR8, -XC(O)NR7R8, -XC(O)NR7XNR7R8, -XNR7C(O)R8, -XR9; where X denotes a bond or C1-4alkylen;
R7and R8independent Vybrat from the group consisting of hydrogen and C1-4of alkyl; and R9choose from C5-6geterotsiklicheskie and C5-6heteroaryl; where these heteroseksualci or heteroaryl contain 1-2 heteroatoms selected from nitrogen and oxygen, and named heteroseksualci or heteroaryl R9optionally substituted radical selected from the group consisting of C1-4the alkyl and-XOR7;
where X and R7described above;
R10selected from hydrogen and C1-6of alkyl;
R15Vybrat from halogroup,1-6of alkyl, C1-6alkoxygroup, galodamadruga of alkyl, galataraseray alkoxygroup; and
R16selected from-NR12C(O)R13, -NR12C(O)NR12R13and-NR12S(O)0-2R13; where R12means hydrogen; R13selected from phenyl, C5-10heteroaryl,5-6geterotsiklicheskie; where any phenyl, heteroaryl, cycloalkyl or heteroseksualci contain 1-2 heteroatoms selected from nitrogen and oxygen, and named heteroseksualci or hetero is the Rila R 13optionally substituted from 1 to 3 radicals independently selected from halogroup, C1-6of alkyl, galodamadruga1-6of alkyl, C1-6alkoxygroup, galataraseray1-6alkoxygroup, -XNR7R8, phenyl-C0-4of alkyl, C5-6heteroaryl-C0-4of alkyl, C5-6heteroseksualci-C0-4alkoxygroup and C5-6heteroseksualci-C0-4of alkyl; where X, R7and R8described above, and where any phenyl, cycloalkyl, heteroaryl, or heterologously Deputy contain 1-2 heteroatoms selected from nitrogen and oxygen, and named heteroseksualci or heteroaryl R13optional optionally substituted from 1 to 3 radicals independently selected from halogroup,1-6of alkyl, galodamadruga1-6of alkyl, replacement C1-6of alkyl, C1-6alkoxygroup,5-6geterotsiklicheskie and galataraseray1-6alkoxygroup.

3. The compound according to claim 2, where R5selected from the group including hydrogen, morpholinoethyl, cyclopropyl, methyl, 3-(2-oxopyrrolidin-1-yl)propyl, benzo[1,3]dioxol-5-yl, 3-(4-methylpiperazin-1-yl)propyl, hydroxymethylene, (1-hydroxyethyl)phenyl, morpholinopropan, pyridinyl, methylcarbamyl, methylsulphonyl, methylpyridine, aminocyclohexane, piperidinyl, methylpiperazine, dimethylpyrazole, methylpyrazole, dimetilpyridine, methylpyridine, ethylpiperidine, aminocarbonylmethyl, cyanopyridine, dimethylaminoethyl, methoxyethyl, methylpyrrolidinyl, aripirazole, dimethylaminopropyl, isopropyl, furylmethyl, methylpiperazine, benzo[1,3]dioxol-5-ylmethyl, 2-methyl-6-morpholine-4-espiridion-3-yl, methylpyrimidine, methoxypyridine, forfinal, diethylaminoethylamine, pyridinylmethyl, triazolylmethyl, methylpyrazine, imidazolidinyl, aminocarbonylmethyl; or R5and R6together with the nitrogen atom to which they are both attached, form a group selected from morpholinopropan, piperidinyl and piperazinil, optionally substituted by a group selected from ethyl, pyridinyl and morpholinopropan.

4. The compound according to claim 3, where R16selected from-NHC(O)R13, -NHC(O)other13and-NHS(O)2R13; where R13selected from phenyl, pyridazinyl, pyridinyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, khinoksalinona, tanila and thiazolyl; where R13optionally substituted from 1 to 3 radicals independently selected from methyl, tert-butyl, geograpy, trifloromethyl, diethylaminopropyl, dimethylaminopropyl, benzyl, piperidinylmethyl, pyrrolidinyloxy, ethylpiperazine, morpholinopropan, methylpiperazine, methylpiperazine, ethylpiperazine, methylimidazole, morpholinomethyl is a, pyrrolidinylcarbonyl, piperazinylmethyl, hydroxypiperidine, 1 methylpiperidin-4-lexigraphy, piperidinyloxy, methylpyrazine, pyrazinyl and hydroxyethylpiperazine.

5. A compound selected from the group including
N-[4-methyl-3-(1-{6-[4-(2-morpholine-4-retil)phenylamino] pyrimidine-4-yl}-1H-imidazol-2-ylamino)phenyl]-3-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-(4-ethylpiperazin-1-yl)-5-cryptomelane,
N-(4-methyl-3-{1-[6-(2-morpholine-4-ylethylamine)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-cryptomelane,
N-{4-methyl-3-[1-(6-methylaminopropyl-4-yl)-1H-imidazol-2-ylamino]phenyl}-3-cryptomelane,
N-[4-methyl-3-(1-{6-[3-(2-oxopyrrolidin-1-yl)propylamino]pyrimidine-4-yl}-1H-imidazol-2-ylamino)phenyl]-3-cryptomelane,
N-(3-{1-[6-(benzo[1,3]dioxol-5-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}-4-were)-3-cryptomelane,
N-[4-methyl-3-(1-{6-[3-(4-methylpiperazin-1-yl)propylamino]pyrimidine-4-yl}-1H-imidazol-2-ylamino)phenyl]-3-cryptomelane,
{6-[2-(2-chlorpheniramine)imidazol-1-yl]pyrimidine-4-yl}cyclopropylamine,
(3-{6-[2-(2-chlorpheniramine)imidazol-1-yl]pyrimidine-4-ylamino}phenyl)methanol,
1-(3-{6-[2-(2-chlorpheniramine)imidazol-1-yl]pyrimidine-4-ylamino}Fe who yl)ethanol,
{6-[2-(2-chlorpheniramine)imidazol-1-yl]pyrimidine-4-yl}-[4-(2-morpholine-4-retil)phenyl]amine,
{6-[2-(2-chlorpheniramine)imidazol-1-yl]pyrimidine-4-yl}-(4-(morpholine-4-ylphenyl)amine,
N-(3-{6-[2-(2-chlorpheniramine)imidazol-1-yl]pyrimidine-4-ylamino}phenyl)acetamide", she
1-(3-{6-[2-(2-chlorpheniramine)imidazol-1-yl]pyrimidine-4-ylamino}propyl)pyrrolidin-2-it,
benzo[1,3]dioxol-5-yl{6-[2-(2-chlorpheniramine)imidazol-1-yl]pyrimidine-4-yl}amine,
{6-[2-(2-chlorpheniramine)imidazol-1-yl]pyrimidine-4-yl}pyridine-3-ylamine,
N-(4-methyl-3-{1-[6-(pyridine-3-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
{6-[2-(2-chlorpheniramine)imidazol-1-yl]pyrimidine-4-yl}-(6-methylpyridin-3-yl)amine,
N-(4-methyl-3-{1-[6-(6-methylpyridin-3-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-morpholine-4-yl-5-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-(4-methylpiperazin-1-yl)-5-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-(4-ethylpiperazin-1-yl)-5-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-4-morpholine-4-yl-3-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-4-(4-ethylpiperazin-ylmethyl)3-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-4-(4-methylpiperazin-1-ylmethyl)-3-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-(4-Mei-1-yl)-5-cryptomelane,
3-(4-Mei-1-yl)-N-{4-methyl-3-[1-(6-methylaminopropyl-4-yl)-1H-imidazol-2-ylamino]phenyl}-5-cryptomelane,
N-{4-methyl-3-[1-(6-methylaminopropyl-4-yl)-1H-imidazol-2-ylamino]phenyl}-4-morpholine-4-yl-3-cryptomelane,
3-(4-ethylpiperazin-1-yl)-N-{4-methyl-3-[1-(6-methylaminopropyl-4-yl)-1H-imidazol-2-ylamino]phenyl}-5-cryptomelane,
N-{4-methyl-3-[1-(6-methylaminopropyl-4-yl)-1H-imidazol-2-ylamino]phenyl}-3-(4-methylpiperazin-1-yl)-5-cryptomelane,
N-{3-[1-(6-methylaminopropyl-4-yl)-1H-imidazol-2-ylamino]phenyl}-4-(4-methylpiperazin-1-ylmethyl)-3-cryptomelane,
3-(4-ethylpiperazin-ylmethyl)-N-{4-methyl-3-[1-(6-methylaminopropyl-4-yl)-N-imidazol-2-ylamino]phenyl)-5-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-4-morpholine-4-ylmethyl-3-cryptomelane,
N-{4-methyl-3-[1-(6-methylaminopropyl-4-yl)-1H-imidazol-2-ylamino]phenyl}-4-morpholine-4-ylmethyl-3-cryptomelane,
N-{3-[1-(6-aminopyridin-4-yl)-1H-imidazol-2-ylamino]-4-were}-4-(4-ethylpiperazin-1-ylmethyl)-3-cryptomelane,
N-{3-[1-(6-aminopyridin-4-yl)-1H-imida the ol-2-ylamino]-4-were}-4-(4-methylpiperazin-1-ylmethyl)-3-cryptomelane,
N-{3-[1-(6-aminopyridin-4-yl)-1H-imidazol-2-ylamino]phenyl}-3-(4-Mei-1-yl)-5-cryptomelane,
N-{3-[1-(6-aminopyridin-4-yl)-1H-imidazol-2-ylamino]-4-were}-4-morpholine-4-yl-3-cryptomelane,
N-{3-[1-(6-aminopyridin-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-(4-ethylpiperazin-1-yl)-5-cryptomelane,
N-{3-[1-(6-aminopyridin-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-(4-methylpiperazin-1-yl)-5-cryptomelane,
N-{3-[1-(6-aminopyridin-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-morpholine-4-ylmethyl-5-cryptomelane,
3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-5-methoxy-N-[4-(2-Mei-1-yl)-3-triptoreline]benzamid,
N-{3-[1-(6-acetylpiperidine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-cryptomelane,
N-{3-[1-(6-methanesulfonylaminoethyl-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-cryptomelane,
N-{3-[1-(2-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-cryptomelane,
3-[1-(2-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-methyl-N-[4-(2-Mei-1-yl)-3-triptoreline]benzamid,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-piperazine-1-ylmethyl-5-cryptomelane,
N-{3-[1-(6-aminopyridin-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-piperazine-1-ylmethyl-5-cryptomelane,
N-{3-[1-(6-cycloprop aminopyrimidine-4-yl)-1H-imidazol-2-ylamino]-5-methoxyphenyl}-4-(4-methylpiperazin-1-ylmethyl)-3-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-5-methoxyphenyl}-3-(4-ethylpiperazin-1-ylmethyl)-5-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were)-3-(piperidine-4-yloxy)-5-cryptomelane,
N-{3-[1-(6-aminopyridin-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-(piperidine-4-yloxy)-5-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-5-methoxyphenyl}-3-(4-pyrrolidin-1-reparacin-1-yl)-5-cryptomelane,
1-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-[4-(2-Mei-1-yl)-3-triptoreline]urea,
1-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-[4-(4-ethylpiperazin-1-ylmethyl)-3-triptoreline]urea,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide pyridazin-4-carboxylic acid,
2-chloro-N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}isonicotinamide,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide, furan-2-carboxylic acid,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide 1-methyl-1H-pyrrole-2-carboxylic acid,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide of 1H-imidazole-2-carboxylic acid,
N-{3-[1-(6-cyclopropyl inoperative-4-yl)-1H-imidazol-2-ylamino]-4-were}-4-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-6-nicotine amide,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide 1-tert-butyl-5-methyl-1H-pyrazole-3-carboxylic acid,
N-[4-(4-ethylpiperazin-1-ylmethyl)-3-triptoreline]-4-methyl-3-{1-[6-(2-morpholine-4-yl-ethylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}benzamide,
3-(4-Mei-1-yl)-N-(4-methyl-3-{1-[6-(2-morpholine-4-ylethylamine)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-5-cryptomelane,
4-methyl-N-[4-(2-Mei-1-yl)-3-triptoreline]-3-{1-[6-(2-morpholine-4-ylethylamine)pyrimidine-4-yl]-1H-imidazol-2-ylamino}benzamide,
N-(4-methyl-3-{1-[6-(2-morpholine-4-ylethylamine)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-(1-methylpiperidin-4-yloxy)-5-cryptomelane,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide pyrazin-2-carboxylic acid,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide 5-methylpyrazine-2-carboxylic acid,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide cinoxacin-6-carboxylic acid,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide 5-tert-butyl-2-methyl-4-morpholine-4-ilmatieteen-3-carboxylic acid,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino] -4-were}amide 5-tert-butyl--methyl-2H-pyrazole-3-carboxylic acid,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide of 2-benzyl-5-tert-butyl-2H-pyrazole-3-carboxylic acid,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-(piperidine-4-ylamino)-5-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-(pyrrolidin-2-ylethoxy)-5-cryptomelane,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide 5-tert-butyl-2-methylfuran-3-carboxylic acid,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide 5-tert-butyl-3-methylfuran-3-carboxylic acid,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide 5-tert-butyl-2-diethylaminophenyl-3-carboxylic acid,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide 5-tert-butyl-4-diethylamino-2-methylfuran-3-carboxylic acid,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide 5-tert-butylthiophene-2-carboxylic acid,
(4-methyl-3-{1-[6-(2-morpholine-4-ylethylamine)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)amide 5-tert-butyl-3-methylfuran-2-carboxylic acid,
(4-methyl-3-{1-[6-(2-morpholine-4-ylethylamine)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)amide 5-tert-butylthiophene-2-carboxylic acid,
(4-methyl-3-{1-[6-(2-morpholine-4-ylethylamine)pyrimid is n-4-yl]-1H-imidazol-2-ylamino}phenyl)amide 5-tert-butyl-2-methylfuran-3-carboxylic acid,
N-(3-{1-[6-(4-aminocyclohexane)pyrimidine-4-yl]-1H-imidazol-2-ylamino}-4-were)-3-cryptomelane,
N-(4-methyl-3-{1-[6-(piperidine-4-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-[4-methyl-3-(1-{6-[2-(4-methylpiperazin-1-yl)-ethylamino]pyrimidine-4-yl}-1H-imidazol-2-ylamino)phenyl]-3-cryptomelane,
N-(3-{1-[6-(2,5-dimethyl-2H-pyrazole-3-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}-4-were)-3-cryptomelane,
N-(4-methyl-3-{1-[6-(4-methylpiperazin-1 ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-(4-methyl-3-{1-[6-(2-methyl-2H-pyrazole-3-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino} phenyl)-3-cryptomelane,
N-(3-{1-[6-(2,6-dimethylpyridin-3-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}-4-were)-3-cryptomelane,
N-(4-methyl-3-{1-[6-(2-methylpyridin-3-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-(4-methylpiperazin-1-yl)-5-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-[4-(2-hydroxyethyl)piperazine-1-yl]-5-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-piperazine-1-yl-5-cryptomelane,
N-{4-chloro-3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]phenyl}Ben is amide,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-forfinal}benzamide,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-2-were}benzamide,
N-{5-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-2-forfinal}benzamide,
N-{5-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-2-were}benzamide,
N-{4-chloro-3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]phenyl}-4-morpholine-4-ylmethyl-3-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-forfinal}-4-morpholine-4-ylmethyl-3-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-2-were}-4-morpholine-4-ylmethyl-3-cryptomelane,
N-{4-chloro-3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]phenyl}-3-(4-Mei-1-yl)-5-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-forfinal}-3-(4-Mei-1-yl)-5-cryptomelane,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-2-were}-3-(4-Mei-1-yl)-5-cryptomelane,
N-{5-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-2-forfinal}-3-(4-Mei-1-yl)-5-cryptomelane,
N-{5-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-2-were}-3-(4-Mei-1-yl)-5-cryptomelane,
N-{3-[1-(6-cyclopropylamino pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methoxyphenyl}benzamide,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-triftoratsetilatsetonom,
3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-methyl-N-(3-triptoreline)benzosulfimide,
N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-forfinal}-3-dimethylamino-5-cryptomelane,
N-{5-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-2-were}-3-dimethylamino-5-cryptomelane,
N-{4-chloro-3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]phenyl}-3-dimethylamino-5-cryptomelane,
3-(4-Mei-1-yl)-N-(4-methyl-3-{1-[6-(pyridine-2-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-5-cryptomelane,
4-(4-ethylpiperazin-1-ylmethyl)-N-(4-methyl-3-{1-[6-(pyridine-2-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
3-(4-ethylpiperazin-1-yl)-N-(4-methyl-3-{1-[6-(pyridine-2-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-5-cryptomelane,
4-chloro-N-(4-methyl-3-{1-[6-(pyridine-2-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-[3-(1-{6-[5-(4-ethylpiperazin-1-yl)pyridine-2-ylamino]pyrimidine-4-yl}-1H-imidazol-2-ylamino)-4-were]-3-cryptomelane,
N-(4-methyl-3-{1-[6-(4-methylpyridin-2-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-(3-{1-[6-(4,6-dimethylpyridin-2-ylamino)pyrimidine-4-yl]-1H-they shall Gasol-2-ylamino}-4-were)-3-cryptomelane,
6-(6-{2-[2-methyl-5-(3-triphtalocyaninine)phenylamino]imidazol-1-yl}pyrimidine-4-ylamino)nicotinamide,
N-(4-methyl-3-{1-[6-(5-methylpyridin-2-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-(3-{1-[6-(5-cyano-2-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}-4-were)-3-cryptomelane,
4-chloro-N-{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-cryptomelane,
4-chloro-N-(4-methyl-3-{1-[6-(2-morpholine-4-ylethylamine)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
(4-methyl-3-{1-[6-(2-morpholine-4-yl-ethylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)amide 5-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid,
N-(3-{1-[6-(2-diethylaminoethylamine)pyrimidine-4-yl]-1H-imidazol-2-ylamino}-4-were)-3-cryptomelane,
N-(4-methyl-3-{1-[6-(3-morpholine-4-ylpropionic)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-(3-{1-[6-(2-methoxyethylamine)pyrimidine-4-yl]-1H-imidazol-2-ylamino}-4-were)-3-cryptomelane,
N-[4-methyl-3-(1-{6-[2-(1-methylpyrrolidine-2-yl)-ethylamino]pyrimidine-4-yl}-1H-imidazol-2-ylamino)phenyl]-3-cryptomelane,
N-(4-methyl-3-{1-[6-(pyridine-2-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-[4-methyl-3-(1-pyrimidine-4-yl-1H-imidazol-2-ylamino)phenyl]-3-cryptomelane,
N-[4-methyl-3-(1-pyrimidine-2-yl-1H-they are the azole-2-ylamino)phenyl]-3-cryptomelane,
N-{4-methyl-3-[1-(4-methylaminopropyl-2-yl)-1H-imidazol-2-ylamino]phenyl}-3-cryptomelane,
N-{4-methyl-3-[1-(2-methylaminopropyl-4-yl)-1H-imidazol-2-ylamino]phenyl}-3-cryptomelane,
N-(4-methyl-3-{1-[4-(2-morpholine-4-ylethylamine)pyrimidine-2-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-(4-methyl-3-{1-[2-(2-morpholine-4-ylethylamine)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-(3-{1-[6-(2-ethyl-2H-pyrazole-3-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}-4-were)-3-cryptomelane,
N-(3-{1-[6-(3-dimethylaminopropylamine)pyrimidine-4-yl]-1H-imidazol-2-ylamino}-4-were)-3-cryptomelane,
N-{3-[1-(6-isopropylpyrimidine-4-yl)-1H-imidazol-2-ylamino]-4-were}-3-cryptomelane,
N-[3-(1-{6-[(furan-3-ylmethyl)amino]pyrimidine-4-yl}-1H-imidazol-2-ylamino)-4-were]-3-cryptomelane,
N-[4-methyl-3-(1-{6-[3-(4-methylpiperazin-1-yl)propylamino]pyrimidine-4-yl}-1H-imidazol-2-ylamino)phenyl]-3-cryptomelane,
N-[3-(1-{6-[(benzo[1,3]dioxol-5-ylmethyl)amino]pyrimidine-4-yl}-1H-imidazol-2-ylamino)-4-were]-3-cryptomelane,
N-(4-methyl-3-{1-[6-(2-methyl-6-morpholine-4-espiridion-3-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-(4-methyl-3-{1-[6-(4-methylpyrimidin-2-ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino} phenyl)-3-cryptomelane,
N-(3-{1-[6-(6-methoxypyridine-3-ylamino)p is rimidine-4-yl]-1H-imidazol-2-ylamino}-4-were)-3-cryptomelane,
N-{4-methyl-3-[1-(6-morpholine-4-Yeremey-4-yl)-1H-imidazol-2-ylamino]phenyl}-3-cryptomelane,
N-(3-{1-[6-(4-ethylpiperazin-1-yl)pyrimidine-4-yl]-1H-imidazol-2-ylamino}-4-were)-3-cryptomelane,
N-(3-{1-[6-(3-forgenerating)pyrimidine-4-yl]-1H-imidazol-2-ylamino}-4-were)-3-cryptomelane,
N-(3-{1-[6-(3-dimethylaminopropylamine)pyrimidine-4-yl]-1H-imidazol-2-ylamino}-4-were)-3-cryptomelane,
N-[4-methyl-3-(1-{6-[(pyridine-3-ylmethyl)amino]pyrimidine-4-yl}-1H-imidazol-2-ylamino)phenyl]-3-cryptomelane,
N-[4-methyl-3-(1-{6-[(pyridine-4-ylmethyl)amino]pyrimidine-4-yl}-1H-imidazol-2-ylamino)phenyl]-3-cryptomelane,
N-(4-methyl-3-{1-[6-(4-(morpholine-4-reparacin-1-yl)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-[4-methyl-3-(1-{6-[(thiazole-2-ylmethyl)amino]pyrimidine-4-yl}-1H-imidazol-2-ylamino)phenyl]-3-cryptomelane,
N-[4-methyl-3-(1-{6-[(pyridine-2-ylmethyl)amino]pyrimidine-4-yl}-1H-imidazol-2-ylamino)phenyl]-3-cryptomelane,
N-[4-methyl-3-(1-{6-[(6-methylpyridin-2-ylmethyl)amino]pyrimidine-4-yl}-1H-imidazol-2-ylamino)phenyl]-3-cryptomelane,
N-(4-methyl-3-{1-[6-(4-pyridine-2-reparation-1-yl)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-(3-{1-[6-(3-imidazol-1-ylpropionic)pyrimidine-4-yl]-1H-imidazol-2-ylamino)-4-were)-3-cryptomelane,
N-(4-methyl-3-{1-[6-(pyrazin-2-ylamino)p is rimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-(3-{1-[6-(3-formamidopyrimidine)pyrimidine-4-yl]-1H-imidazol-2-ylamino}-4-were)-3-cryptomelane,
4-methyl-3-{1-[6-(2-morpholine-4-ylethylamine)pyrimidine-4-yl]-1H-imidazol-2-ylamino}-N-(3-triptoreline)benzamid,
4-methyl-3-{1-[6-(4-methylpiperazin-1 ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}-N-(3-triptoreline)benzamid,
N-(4-chloro-3-triptoreline)-4-methyl-3-{1-[6-(2-morpholine-4-ylethylamine)pyrimidine-4-yl]-1H-imidazol-2-ylamino}benzamide,
N-(4-chloro-3-triptoreline)-4-methyl-3-{1-[6-(4-methylpiperazin-1 ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}benzamide,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide 1-tert-butyl-5-(4-methylpiperazin-1-ylmethyl)-1H-pyrazole-3-carboxylic acid,
{3-[1-(6-cyclopropylamine-4-yl)-1H-imidazol-2-ylamino]-4-were}amide 1-tert-butyl-(5-morpholine-4-ylmethyl)-1H-pyrazole-3-carboxylic acid, N-(4-tert-butylthiazole-2-yl)-4-methyl-3-{1-[6-(2-morpholine-4-ylethylamine)pyrimidine-4-yl]-1H-imidazole-2-ylamino}benzamide,
N-(4-tert-butylthiazole-2-yl)-4-methyl-3-{1-[6-(4-methylpiperazin-1 ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}benzamide,
N-(5-tert-butyl-2-methyl-2H-pyrazole-3-yl)-4-methyl-3-{1-[6-(4-methylpiperazin-1 ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}benzamide,
N-(4-methyl-3-{1-[6-(4-methylpiperazin-1 ylamino)pyrimidine-4-yl]-1H-imidazol-2-ylamino}phenyl)benzamide,
N-(5-tert-butyl-2-methyl-2H-pyrazole-3-yl)-4-methyl-{1-[6-(2-morpholine-4-ylethylamine)pyrimidine-4-yl]-1H-imidazol-2-ylamino}benzamide,
N-(4-methyl-3-{1-[2-(2-morpholine-4-ylethylamine)pyridine-4-yl]-1H-imidazol-2-ylamino}phenyl)-3-cryptomelane,
N-{3-[1-(4-acetylpiperidine-2-yl)-1H-imidazol-2-ylamino]-4-were}-3-cryptomelane and
2-{2-[2-methyl-5-(3-triphtalocyaninine)phenylamino]imidazol-1-yl} isonicotinamide.

6. Pharmaceutical composition having properties kinase inhibitor selected from the group Abl, BCR-Abl, PDGF-R, trkB, c-SRC, BMX, FGFR3, b-RAF, SGK, Tie2, Lck, JNK2α2, MKK4, c-RAF, MKK6, SAPK2α and SAPK2β comprising a therapeutically effective amount of a compound according to any one of claims 1, 2 or 5 in combination with a pharmaceutically acceptable filler.

7. A method of inhibiting the activity of a kinase selected from the group Abl, BCR-Abl, PDGF-R, trkB, c-SRC, BMX, FGFR3, b-RAF, SGK, Tie2, Lck, JNK2α2, MKK4, c-RAF, MKK6, SAPK2α and SAPK2β, including the introduction of a therapeutically effective amount of a compound according to any one of claims 1, 2 or 5.

8. The use of compounds according to any one of claims 1, 2 or 5 to obtain drugs for the treatment of diseases in which the activity of Abl kinase, BCR-Abl, PDGF-R, trkB, c-SRC, BMX, FGFR3, b-RAF, SGK, Tie2, Lck, JNK2α2, MKK4, c-RAF, MKK6, SAPK2α and/or SAPK2β contributes to the pathology and/or symptomatology of the disease.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel 1-substituted-3-[(1E)-1-alkenyl]-4-(5-alkoxy-1,2-dimethyl-1H-indol-3-yl)-1H-pyrrole-2,5-diones of general formula

, where R1=C1-C6alkyl, R2=C1-C6 alkyl, R3=CH2C6H5, C6H5.

EFFECT: obtaining novel compounds which can be used as fluorescent photochromes.

4 cl, 1 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to use of existing and novel N-sulfamoyl- N'-arylpiperazines and their physiologically compatible acid-addition salts of formula I , where Ar denotes a monocyclic or bicyclic C6-C10aryl in which ring carbon atoms are optionally substituted with 1-3 nitrogen or oxygen atoms, and/or where the C6-C10aryl ring system optionally contains 3-5 double bonds, and/or where the C6-C10aryl ring system is optionally substituted with 1 or 2 substitutes which can be identical or different and which can be selected from a group containing halogen, trifluoromethyl, cyano group, nitro group, C1-C4alkyl, C1-C4alkoxy group, C1-C4alkylsulfonyl; and two oxygen atoms which are bonded to two neighbouring carbon atoms of the C6-C10aryl ring system and are bonded by a C1-C2alkylene bridge; or where the C6-C10aryl ring system is substituted with phenyl which can optionally be substituted in the phenyl ring by one substitute which can be selected from a group containing halogen; for preventing or treating obesity and related diseases.

EFFECT: design of a method of obtaining the said compounds and a pharmaceutical composition based on the said compounds.

25 cl, 9 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a compound having the structural formula I , or its pharmaceutically acceptable salt, ester or amide, where A has the structure , where each bond in A, represented by a dotted and a solid line, represents a carbon-carbon single bond; each of a, b and c is a carbon atom; each of e, f, g and h is a carbon atom; X is nitrogen; X' is C; L is absent; each n equals 1; Y is nitrogen; W is nitrogen; R1 is hydrogen; each of R2, R3 and R4 is a hydrogen atom; each of R6, R8 and R9 is a hydrogen atom; R5 is selected from a group consisting of halogen, C1-6alkyl, optionally substituted with a hydroxy group, and C1-6alkoxy; R7 is selected from a group consisting of halogen, C1-6alkyl and perhalogenalkyl; Z is selected from a group consisting of NR11, oxygen and CH2; R11 is hydrogen; and each bond in formula I, represented by a dotted and a solid line, is a carbon-carbon double bond. The invention also relates to a method for synthesis of a formula V compound, a pharmaceutical composition based on a formula I compound, methods of treating psychoneurological disorders, a pharmaceutical composition containing a formula I compound and a psychoneurological agent.

EFFECT: obtaining novel compounds useful for modulating muscarine receptor activity.

37 cl, 1 tbl, 141 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to phenylalanine derivatives and their pharmaceutically acceptable salts. In formula (1) R11 is a hydroxyl group, an alkoxyl group having 1-6 carbon atoms, which can be substituted with a methoxy group, cycloalkoxyl group having 3-6 carbon atoms, or a benzyloxy group; R12 and R13 each independently represents a hydrogen atom, alkyl group having 1-6 carbon atoms, cycloalkyl group having 3-6 carbon atoms, acetyl group or methyloxycarbonyl group, or N(R12)R13 is a 1-pyrrolidinyl group, 1-piperidinyl group, 4-morpholinyl group; R14 is a methyl group; R1' is a hydrogen atom, fluorine atom; X1 is -CH(R1a)-, -CH(R1a)CH(R1b)-, -CH(R1a)CH(R1b)CH(R1c)-, -N(R1a)CH(R1b)CH(R1c)-, -OCH(R1a)CH(R1b)-, -OCH(R1a)CH(R1b)CH(R1c)- or 1,3-pyrrolidinylene, where R1a, R1b, each independently represents a hydrogen atom or a methyl group, and R1c is a hydrogen atom; Y11 and Y12 represent any of the combinations (CI, Cl), (CI, Me), (CI, F). Invention also relates to phenylalanine derivatives of formulae (2)-(14), given in the formula of invention.

EFFECT: obtaining a pharmaceutical composition having antagonistic effect on α4-integrin, containing a phenylalanine derivative as an active ingredient, a α4-integrin antagonist and a therapeutic agent.

65 cl, 51 tbl, 244 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula Ia: and its pharmaceutically acceptable salt, where: p equals 0 or 1; n assumes values from 1 to 3, q equals 1; R5 is selected from hydrogen, -XNR7R8, pyrimidine-C0-4alkyl, pyridine-C0-4alkyl, phenyl, C3-10cycloalkyl-C0-4alkyl and C3-6heterocycloalkyl-C0-4alkyl, where C3-6heterocycloalkyl is a saturated monocyclic ring system containing the said number of atoms, provided that one or more of the said carbon atoms is substituted with O or NR, where R is hydrogen or C1-4alkyl; R7 and R8 represent C1-4alkyl; R6 denotes hydrogen; or R5 and R6 together with a nitrogen atom to which they are both bonded form morpholine or piperidine; where any piperdine-C0-4alkyl, piperidine-C0-4alkyl or C3-10cycloalkyl-C0-4alkyl of substitute R5 or a combination of radicals R5 and R6 can be optionally substituted with 1-2 radicals which are independently selected from -XNR7R8 and -XOR7, the said phenyl of substitute R5 is substituted with a -XR9 group, the said C3-6heterocycloalkyl-C0-4alkyl of substitute R5 is optionally substituted with a -XOR7 group, where X is a single bond or C1-4alkylene; R7 and R8 are independently selected from hydrogen and C1-4alkyl; R9 is selected from C3-10heterocycloalkyl which is a saturated monocyclic ring system containing the said number of atoms, provided that one or more of the said carbon atoms is substituted with O or NR, where R is as given above; R10 denotes hydrogen; R15 is selected from halogen, C1-6alkyl and C1-6alkoxy; and R16 is selected from halogen, methoxy, nitro, -NR12C(O)R13, -C(O)NR12R12, -NR12R12, -C(O)OR12 and -C(O)NR12R13; each R12 is selected from hydrogen and C1-6alkyl; R13 is selected from phenyl, thienyl, pyrazolyl, pyridinyl or isoxazolyl, where any phenyl, thienyl, pyrazolyl, pyridinyl or isoxazolyl of substitute R13 can be optionally substituted with 1-2 radicals which are independently selected from halogen, C1-6alkyl, halogen-substituted C1-6alkyl, imidazole-C0-4alkyl, C3-10cycloalkyl, C3-10heterocycloalkyl-C0-4alkoxy and C3-10heterocycloalkyl-C0-4alkyl; where the said C3-10heterocycloalkyl-C0-4alkoxy and C3-10heterocycloalkyl-C0-4alkyl each represent a saturated monocyclic ring system containing the said number of atoms, provided that one or more of the said carbon atoms is substituted with O or NR, where R assumes values given above; and the said C3-10heterocycloalkyl-C0-4alkoxy and C3-10heterocycloalkyl-C0-4alkyl can each be optionally substituted with 1 radical independently selected from C1-6alkyl, hydroxyl-substituted C1-6alkyl and NR7R8, where R7 and R8 assume values given above. The invention also relates to pharmaceutical compositions containing the said compounds.

EFFECT: obtaining novel compounds and compositions based on the said compounds which can be used in medicine for treating and preventing diseases or disorders associated with abnormal or uncontrolled kinase activity, particularly diseases or disorders associated with abnormal activity of kinase c-Src, FGFR3, KDR and/or Lck.

12 cl, 1 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) which are protein tyrosine kinase 1B(PTP-1B) inhibitors and can be used in medicinal preparations for treating and preventing diseases related to high concentration of glucose in blood, for example diabetes and obesity. In formula (I) X is a X-1 group or X-2: , where R1 and R2 are each independently selected from a group consisting of hydrogen, lower alkyl, alkoxy-lower alkyl and hydroxyl-lower alkyl, under the condition that, R1 and R2 both represent hydrogen; R3, R4, R6 and R7 are each independently selected from a group consisting of hydrogen, lower alkyl; lower alkyl substituted with halogen or hydroxy; lower alkoxy; lower alkoxy substituted with halogen, hydroxy or lower alkoxy; hydroxyl, halogen, lower alkylthio, lower alkylsufanyl, lower alkylsufanyl, aminosufonyl, cyano, nitro, carbamoyl, lower mono- or dialkylcarbamoyl, lower alkanoyl, benzoyl, phenyl, phenyl substituted with halogen, phenyloxy, lower mono- or dialkylamino, hydroxy-substituted lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, heterocycloalkyl, hydroxy-substituted heterocycloalkyl, heterocyclyloxy, heterocyclylcarbonyl; where each heterocycloalkyl in the said values represents a 5-6-membr ring containing 1-2 heteroatoms selected from nitrogen and oxygen, and which can be substituted with lower alkyl or phenyl-lower alkyl; carboxyl, lower alkoxycarbonyl and a substitute of formula: ; R8 is selected from a group consisting of hydrogen, lower alkylthio, halogen, alkoxy-lower alkoxy, lower alkoxy, halogen-lower alkyl, hydroxy-lower alkyl; represents a 5-member heteroaromatic ring containing 1 or 2 heteroatoms selected from a group consisting of hydrogen, sulphur and nitrogen; R8 and R9 each independently represents hydrogen or lower alkyl.

EFFECT: novel compounds have useful biological properties.

31 cl, 7 dwg, 152 ex

FIELD: medicine.

SUBSTANCE: invention covers compound 6-amino-4-chloropyrazolo[3,4-d]pyrimidine. Offered compound is made of 2-amino-4,6-dichloropyrimidine by the two-staged method based on a common reaction of selective replacement of hydroxyl group with chlorine atom (chlorodehydroxylation) and replacement of hydrogen atom with carbonyl group followed with ring closure of the product with hydrazine. The declared compound provides a specific inhibiting action on human 8-oxoguanine-DNA-glycosylase enzyme (hOggl).

EFFECT: low-price and available compound, extended range of specific inhibitors of said enzyme and possibility for effective application in medicine.

2 dwg, 2 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to derivatives of substituted pyridazinylamine of formula or to their pharmaceutically acceptable salts or hydrates, where X is C or N; Y is O or S; W is C or N; R1, R2, R3 each independently represents hydrogen or halogen; R4, R5, R6 each independently represents hydrogen, halogen, C1-C8-straight or branched alkyl, C1-C8-straight or branched alkoxy, nitro, cyano, -COOR7, -CH2COOR7, -COR7; R7 independently represents hydrogen or C1-C8-straight or branched alkyl. The invention also relates to a method of producing said compounds, to pharmaceutical compositions containing said compounds and to use of the said compounds as picornavirus inhibitors for preventing and/or treating diseases caused by pircornaviruses.

EFFECT: novel compounds have useful biological properties.

10 cl, 1 tbl, 33 ex

Novel insecticides // 2379301

FIELD: chemistry.

SUBSTANCE: compounds with formula I are described, where each of E and Z is oxygen; A is C1-C6alkylene or a 3-member monocyclic ring system, which can be monosubstituted; Y is C1-C6alkylene; p equals 0; q equals 0 or 1; B represents a 3- or 4-member ring system which is completely or partially saturated and can contain a heteroatom selected from oxygen, possibly substituted; each R1 independently represents halogen, nitro group, C1-C6alkyl; or each R1 independently represents an amino group; n equals 1, 2; each of R2 and R3 represents hydrogen; D represents a group and agronomically acceptable salts of said compounds. Also described is a method of producing formula I compounds, intermediate compounds, a pesticide composition containing a formula I compound, as well as an insect control method and a method of protecting plant propagation material.

EFFECT: novel anthranylamide derivatives have good insecticidal activity.

16 cl, 8 tbl, 19 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds with general formula (I), where W is oxygen or sulphur; X1 and X3 are independently hydrogen or C1-C6-alkoxy; X2 is hydrogen, halogen, C1-C6-alkyl or C1-C6-alkoxy and X4 is hydrogen, Y is in position (N2) or (N3); when Y is in position (N2), Y is C1-C6-alkyl, C1-C6-fluoroalkyl, phenyl, pyridinyl or pyrazinyl; when Y is in position (N3), Y is phenyl, pyridinyl or pyrimidinyl, where phenyl is optionally substituted with one or more atoms or groups selected from halogen, C1-C5 alkyl, C1-C6-alkoxy; the bond in position C4-C5 is a single or double bond; R1 and R2 each independently represent phenyl and C1-C6-alkyl, where at least one of R1 and R2 represents C1-C6-alkyl; or R1 and R2 together with the nitrogen atom to which they are bonded form a cyclic group containing from 4 to 7 links and a nitrogen atom and possibly another heteroatom, such as nitrogen or oxygen, possibly substituted with one or more C1-C6-alkyl groups; or to their pharmaceutically acceptable salts. The invention also relates to methods of producing the proposed compounds with formula (I), and specifically to compounds with formulae (Ia) and (Ib), in which X1, X3, X3, X4 and Y are as described in general formula (I). The invention also relates to intermediate compounds of synthesis of formula (I) compounds - compounds with formulae (Va) and (Vb). In formula (Va) X1, X3 and X4 represent hydrogen; X2 is hydrogen, halogen or C1-C6-alkoxy and Y is C1-C6-alkyl, C1-C6-fluoroalkyl, phenyl, pyridinyl or pyrazinyl; where phenyl is possibly substituted with one or more atoms or groups selected from halogen, C1-C6-alkyl, C1-C6-alkoxy. In formula (Vb) X1 and X3 represent hydrogen or C1-C6-alkoxy; X2 is hydrogen, halogen, C1-C6-alkyl or C1-C6-alkoxy, X4 is hydrogen; Y is phenyl, pyridinyl or pyrmidinyl; phenyl is possibly substituted with one or more atoms or groups selected from halogen, C1-C6-alkyl, C1-C6-alkoxy. The invention also relates to a medicinal agent based on a formula (I) compound or its pharmaceutically acceptable salt for preventing and treating pathologies where peripheral type benzodiazepine receptors take part. The invention also relates to use of formula (I) compounds in preparing the said medicinal agent and to a pharmaceutical composition for preventing and treating pathologies in which peripheral type benzodiazepine receptors take part.

EFFECT: new compounds have useful biological activity.

11 cl, 3 tbl, 6 ex

.

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrimidine derivatives having FAK inhibitory activity of formula (I), where R0 is hydrogen; R1 is a 5- or 6-member heterocycle containing 1 or 2 nitrogen atoms substituted with (C1-C7)alkyl, hydroxyl group, dialkylamino group or a 6-member heterocycle containing one nitrogen atom; R2 is hydrogen; R3 is carbamoyl substituted once or twice with (C1-C7)alkyl; a 5-member heterocycle containing 4 nitrogen atoms; SO2N(R12)R13, where R12 is hydrogen or (lower)alkyl, and R13 is hydrogen, (C1-C7)alkyl, (C1-C7)alkoxy(C1-C7)alkyl, di(C1-C7)alkylamino(C1-C7)alkyl, hydroxy(C1-C7)alkyl, or R12 and R13 together a nitrogen atom with which they are bonded form a 6-member heterocycle containing two nitrogen atoms, where the said heterocycle is not substituted or substituted with (C1-C7)alkyl; R4 is hydrogen; R5 is a halide; R6 is hydrogen; R7 is hydrogen; (C1-C7)alkoxy; carbamoyl which is not substituted or substituted with (lower)alkyl; a 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen atoms, unsubstituted or substituted with di(C1-C7)alkylamino, (C1-C7)alkyl, hydroxy, 6-member heterocycle containing 1 or 2 nitrogen or oxygen ring atoms, unsubstituted or substituted with (C1-C7)alkyl; 6-member heterocycle-oxy containing 1 nitrogen ring atom, unsubstituted or substituted with (C1-C7)alkyl; heterocycle(C1-C7)alkyloxy, where heterocycle denotes a 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen ring atoms which is not substituted or substituted with (C1-C7)alkyl; R8 is hydrogen; halide; (C1-C7)alkoxy, carbamoyl unsubstituted or substituted with (C1-C7)alkyl; heterocycle(C1-C7)alkyloxy, where heterocycle denotes a 5-member heterocycle containing 1 nitrogen ring atom, unsubstituted or substituted with (C1-C7)alkyl; 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen atoms, unsubstituted or substituted with one or two substitutes independently selected from hydroxy, (C1-C7)alkyl, aminocarbonyl and (C1-C7)alkylamino; 6-member heterocycle-oxy, containing 1 nitrogen ring atom, unsubstituted or substituted 1-5 times with (C1-C7)alkyl or di(C1-C7)alkylamino; or R7 and R8 together with atoms with which they are bonded form a 6-member heterocycle containing two nitrogen or oxygen atoms, unsubstituted or substituted once or twice with (C1-C7)alkyl or oxo group; R9 is hydrogen; R10 is (C1-C7)alkoxy, as well as to their pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition and synthesis method.

EFFECT: novel compounds have useful biological activity.

4 cl, 167 ex

FIELD: medicine.

SUBSTANCE: method involves polychemotherapy followed by radiation therapy (RT) with underlying plant-based mouth rinsing and oral administration of Colegel with Derinat and Lidocaine 3 times a day and more often. The polychemotherapy is performed by no more than 2 courses with the radiation started not earlier than in 10-15 days after the polychemotherapy to total basic dose 66-70 Gy and with peripheral blood of an exposed patient analysed for lymphocyte count once in 10 days and more often. If lymphocyte count is 1.2×109/l or less, the following RT sessions are carried out with underlying additional intensive local and system therapy, or the therapy is interrupted for the hemostimulation therapy.

EFFECT: use of the invention allows preventing severity gain in a radiation involvement of oropharyngeal mucosa due to well-timed intensification of local and system therapy, performing a radical RT course and improving clinical effectiveness.

2 cl, 2 ex

FIELD: medicine.

SUBSTANCE: pharmaceutical composition for treating syphilis and viral diseases specified from influenza, human immunodeficiency virus, cytomegalovirus infections, viral hepatitis type A, D, C and herpes infections, containing an amount of polyphenol compounds of sea buckthorn leaves, including at least 60 % of halloellagotannines, flacoside, a pharmacologically acceptable carrier and a substance of licorice extract, or glycyrrhizic acid, or its pharmaceutically acceptable salt, acridonoacetic acid or its pharmaceutically acceptable salt, birch bark extract or betulin taken in therapeutically effective amounts. A method of treating syphilis and viral diseases, including the introduction of the declared pharmaceutical composition by 2-3 doses 3 times a day.

EFFECT: composition exhibits an evident antiviral action with respect to the infections stated above.

22 cl, 1 dwg, 12 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel crystalline modifications of [6-methoxy-5-(2-methoxyphenoxy)-2-pyridin-4-ylpyrimidin-4-yl]amide-5-methylpyridine-2-sulfonic acid, which produces an endothelial antagonistic effect and is suitable for treating diseases associated with abnormal vascular tone and endothelial dysfunction, such as heart failure, pulmonary hypertension etc. The crystalline modification which is denoted modification B is characterised by a powder X-ray diffractogram with characteristic peaks expressed through the d-parametre value (interplanar distance) (Å) obtained on a conventional X-ray powder diffractometre using Cuka radiation: 10.7 (m), 9.4 (m), 8.6 (vs), 8.3 (m), 7.6 (m), 6.7 (m), 6.4 (m), 6.0 (m), 5.69 (m), 5.30 (m), 5.17 (m), 4.95 (vs), 4.76 (m), 4.56 (m), 4.43 (s), 4.13 (vs), 3.80 (s), 3.45 (s), 3.41 (s), 3.37 (s) and 3.03 (m). The invention also relates to crystalline pseudopolymorphous modifications of [6-methoxy-5-(2-methoxyphenoxy)-2-pyridin-4-ylpyrimidin-4-yl]amide-5-methylpyridine-2-sulfonic acid selected from: a) pseudopolymorphous modification, solvate with ethanol, denoted modification D; b) pseudopolymorphous modification, polysolvate with acetone, denoted modification E; c) pseudopolymorphous modification, solvate with tetrahyrofuran, denoted modification F; d) pseudopolymorphous modification, solvate with methanol, denoted modification G; e) pseudopolymorphous modification, solvate with isopropanol, denoted modification H; f) pseudopolymorphous modification, solvate with dichloromethane, denoted modification I; and g) pseudopolymorphous modification, solvate with 2-butanol, denoted modification J. The invention also relates to a method of obtaining crystalline modification B, a pharmaceutical composition and use.

EFFECT: wider field of use of the compounds.

8 cl, 9 dwg, 9 tbl, 12 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, oncology, and can be used for chemoradiation therapy of low-located tumours of rectum and anal canal. For this purpose standard teleirradiation is performed. Additionally performed is conformal intraluminal brachytherapy of high power dose 5-10 Curie 4-6 irradiation sessions with reference dose 3.5 Gy at depth of 10 mm from irradiation source. In addition, on daily basis derivative of capecitabine fluoropyrimidines in amount 600 mg/m2 is introduced per os.

EFFECT: method allows to increase treatment efficiency, increase local response of tumour and reduce risk of metastases development due to exposing tumour to higher tumoricidal doses of irradiation and adding brachytherapy, intake of capecitabine enhancing local regress and reducing risk of tumour metastasis.

3 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, oncology, and can be used for treatment of locally advanced and inoperable cancer of esophagus. For this purpose before beginning chemoradiation therapy argon plasma coagulation of tumour is performed. After that on 1-st, 8-th and 15-th day of the course intraluminal brachytherapy with high power dose 5-10 Curie with single dose 7 Gy is carried out. In addition, on 1-st, 8-th and 15-th day of the course intravenously taxoter 45 mg/m2 and carboplatin AUC 2 are introduced. After that teleirradiation SFD 1.8 Gy 5 fractions/week TFD 40-45 Gy is carried out.

EFFECT: method allows to increase efficiency of chemotherapeutic and radiation effect after preliminarily eliminated by argon plasma coagulation tumour stenosis of esophagus, succession of treatment stages allows to ensure maximal response of tumour, enhance degree of tumour regress and reduce probability of metastasis.

2 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to oncology and can be used for optimisation of Hodgkin's lymphoma of IIIA stage treatment in adults. Method is realised in the following way. In case there are no symptoms of intoxication, patients with histological subtype nodular sclerosis and with histological grade at which 75% and more of cellular nodules contain only dispersed Berezovsky-Stenberg cells located on rich in lymphocytes mixed cellular or fibrohistiocytic background, 2-3 cycles of introductory combined chemical therapy are carried out according to schemes MOPP, MOPPABV or ABVD. After that total or subtotal irradiation of lymphatic nodules is performed.

EFFECT: application of invention allows to determine indications for chemical-radiological therapy taking into account versions of histological structure of tumour, ensures long-term recurrence-free survival rate and reduces treatment toxicity.

2 ex

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine, namely to oncology and can be used in combined treatment of cancer. Versions of pharmaceutical preparation according to the invention include 7-tret-butoxyiminomethylcamptothecin and other chemical therapeutic agent. The inventions also relate to application of 7-tert-butoxyiminomethylcamptothecin for obtaining medication for application in combination with one or several chemical therapeutic agents.

EFFECT: application of the inventions allows to increase anti-tumour effect due to enhancement of cytotoxic effect with respect to tumour cells due to synergetic action of components.

9 cl, 18 tbl, 12 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to oncology, and can be used in metastasis prevention in puncture and surgical management of skin melanoma. The method involves superfacial and subfacial introduction of Klein's solution 20 ml around the tumour.

EFFECT: use of the invention reduces risk of the ingress of tumour cells in greater lymphatic vessels and venules in tumour puncture and surgical management due to spasm of lymphatic blood vessels ensured by Klein's solution.

1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to porphyrin derivatives of formula

and

, where X1, X2, X3, X4, X5, X6, X7, X8 denote halogen atoms or hydrogen atoms and R1, R2, R3, R4 are selected from OH-groups, amino acids, OR-groups, NHR-groups and/or chlorine atoms, where R is an alkyl containing 1-12 carbon atoms. The invention also relates to a method of obtaining said compounds and medicinal agents prepared from said compounds.

EFFECT: possibility of using compounds and medicinal agents in photodynamic therapy of cancerous diseases.

19 cl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrimidine derivatives having FAK inhibitory activity of formula (I), where R0 is hydrogen; R1 is a 5- or 6-member heterocycle containing 1 or 2 nitrogen atoms substituted with (C1-C7)alkyl, hydroxyl group, dialkylamino group or a 6-member heterocycle containing one nitrogen atom; R2 is hydrogen; R3 is carbamoyl substituted once or twice with (C1-C7)alkyl; a 5-member heterocycle containing 4 nitrogen atoms; SO2N(R12)R13, where R12 is hydrogen or (lower)alkyl, and R13 is hydrogen, (C1-C7)alkyl, (C1-C7)alkoxy(C1-C7)alkyl, di(C1-C7)alkylamino(C1-C7)alkyl, hydroxy(C1-C7)alkyl, or R12 and R13 together a nitrogen atom with which they are bonded form a 6-member heterocycle containing two nitrogen atoms, where the said heterocycle is not substituted or substituted with (C1-C7)alkyl; R4 is hydrogen; R5 is a halide; R6 is hydrogen; R7 is hydrogen; (C1-C7)alkoxy; carbamoyl which is not substituted or substituted with (lower)alkyl; a 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen atoms, unsubstituted or substituted with di(C1-C7)alkylamino, (C1-C7)alkyl, hydroxy, 6-member heterocycle containing 1 or 2 nitrogen or oxygen ring atoms, unsubstituted or substituted with (C1-C7)alkyl; 6-member heterocycle-oxy containing 1 nitrogen ring atom, unsubstituted or substituted with (C1-C7)alkyl; heterocycle(C1-C7)alkyloxy, where heterocycle denotes a 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen ring atoms which is not substituted or substituted with (C1-C7)alkyl; R8 is hydrogen; halide; (C1-C7)alkoxy, carbamoyl unsubstituted or substituted with (C1-C7)alkyl; heterocycle(C1-C7)alkyloxy, where heterocycle denotes a 5-member heterocycle containing 1 nitrogen ring atom, unsubstituted or substituted with (C1-C7)alkyl; 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen atoms, unsubstituted or substituted with one or two substitutes independently selected from hydroxy, (C1-C7)alkyl, aminocarbonyl and (C1-C7)alkylamino; 6-member heterocycle-oxy, containing 1 nitrogen ring atom, unsubstituted or substituted 1-5 times with (C1-C7)alkyl or di(C1-C7)alkylamino; or R7 and R8 together with atoms with which they are bonded form a 6-member heterocycle containing two nitrogen or oxygen atoms, unsubstituted or substituted once or twice with (C1-C7)alkyl or oxo group; R9 is hydrogen; R10 is (C1-C7)alkoxy, as well as to their pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition and synthesis method.

EFFECT: novel compounds have useful biological activity.

4 cl, 167 ex

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