2-(piperidin-4-yl)-4-phenoxy- or phenylaminopyrimidine derivatives as non nucleoside reverse transcriptase inhibitors

FIELD: chemistry.

SUBSTANCE: present invention refers to compounds of formula I or their pharmaceutically acceptable salts showing activity with respect to HIV reverse transcriptase, as well as to a based pharmaceutical composition (I). In formula I R1 means phenyl(C1-C3)alkyl, heteroaryl(C1-C3)alkyl, phenyl or heteroaryl optionally substituted by one-three substitutes independently specified in groups (a)-(r), R2 means -CN, -CH=CHCN or halogen; R3 means hydrogen, halogen, amino group, halogen(C1-C6)alkyl, -CN or methyl; R4 means hydrogen, Br or amino group; R5a and R5b independently mean hydrogen, C1-C6alkyl, C1-C6alkoxy group or halogen; R6a and R6b either independently mean hydrogen, or together mean ethylene; X means NH or O. The groups (a)-(r) are such as presented in the patent claim.

EFFECT: preparing pharmaceutically acceptable salts possessing activity with respect to HIV reverse transcriptase.

17 cl, 42 ex, 6 dwg, 5 tbl

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

where R1means phenyl(C1-C3)alkyl, heteroaryl(C1-C3)alkyl, phenyl or heteroaryl where specified heteroaryl selected from the group including pyridinyl, pyridine-N-oxide, pyrimidinyl, thiophenyl, pyrrolyl, thiazolyl, imidazolyl or chenail, and the phenyl or the specified heteroaryl optionally substituted with one to three substituents, independently selected from the group including:
(a) C1-C6alkyl,
(b) C1-C6alkoxygroup,
(c) halogen(C1-C6)alkyl,
(d) halogen(C1-C6)alkoxygroup,
(e) carboxyl,
(f) CONR7aR7b,
(g) C1-C6alkoxycarbonyl,
(h) a cyano or 2-cyanophenyl,
(i) SO2-(C1-C6)alkyl,
(j) SO2NR8aR8b,
(k) halogen,
(l) the nitrogroup,
(m) cyano(C1-C3)alkyl,
(n) NR10aR10b,
(o) NR10aSO2-(C1-C6)and the Kil,
(p) CRllaRllbCORl2,
(q) the hydroxyl and
(r)1-C6alkyl in which one or two hydrogen atoms substituted for IT;
R2means-CN, -CH=CHCN, or halogen;
R3means hydrogen, halogen, amino, halogen(C1-C6)alkyl, -CN or methyl;
R4means hydrogen, Br, or amino group;
R5aand R5bindependently mean hydrogen, C1-C6alkyl, C1-C6alkoxygroup or halogen;
R6aand R6bindependently mean hydrogen or together denote ethylene;
one of R7aand R7bindependently means hydrogen, C1-C6alkyl or C3-C7cycloalkyl, and the other of R7aand R7bselected from the group comprising hydrogen, C1-C6alkyl, C1-C6alkylsulfonyl, hydroxy(C1-C6)alkyl, (C1-C3)alkylamino(C1-C6)alkyl, di(C1-C3alkyl)-amino(C1-C6)alkyl, amino(C1-C6)alkyl;
R8aand R8bmean hydrogen;
R10aR10bindependently mean hydrogen, C1-C3alkyl or C1-C6acyl;
R11ameans hydrogen or halogen;
R11bmeans hydrogen, halogen, C1-C6alkyl, C1-C6alkoxygroup, hydroxy(C1-C6)alkyl or HE;
R12means hydroxyl, C1- 6alkoxygroup or NR7aR7b;
X is NH or O;
or its pharmaceutically acceptable salt.

2. The compound according to claim 1, where R7a, R7b, R8a, R8bmean hydrogen.

3. The compound according to claim 1, where R1means optionally substituted phenyl.

4. The compound according to claim 3, where R1means phenyl, substituted groups CONR7aR7b, SO2NR8aR8bor SO2-(C1-C6)alkyl and optionally additionally substituted by one or two substituents selected from the group comprising (a) C1-C6alkyl, (b) C1-C6alkoxygroup, (C) halogen(C1-C6)alkyl, (d) halogen(C1-C6)alkoxygroup, (e) carboxyl, (f) C1-C6alkoxycarbonyl, (h) cyano, (i) C1-C6allmenalp, (j) halogen, and (k) the nitrogroup, a R5a, R5bmean CH3.

5. The compound according to claim 4, where R1means phenyl, substituted groups CONH2, SO2NH2or SO2-(C1-C3)alkyl and optionally additionally substituted by one or two substituents selected from the group comprising (a) C1-C6alkyl, (b) C1-C6alkoxygroup, (C) halogen(C1-C6)alkyl, (d) halogen(C1-C6)alkoxygroup, (e) carboxyl, (f) C1-C6alkoxycarbonyl, (h) cyano, (i) C1 -C6allmenalp, (j) halogen, and (k) a nitro-group.

6. The compound according to claim 5, where R3means hydrogen or bromine, R4means hydrogen.

7. The compound according to claim 5, where R1means phenyl, substituted in position 3 groups CONH2, SO2NH2or C1-C6alkylsulfonyl, and optionally substituted by one or two substituents selected from the group comprising (a)1-C6alkyl, (b) C1-C6alkoxygroup, (C) halogen(C1-C6)alkyl, (d) halogen(C1-C6)alkoxygroup, (e) carboxyl, (f) C1-C6alkoxycarbonyl, (h) cyano, (i) C1-C6allmenalp, (j) halogen, and (k) a nitro-group.

8. The connection according to claim 7, where R1mean 3-carboxamidine, 3-aminosulphonylphenyl or 3-methanesulfonyl, R3means hydrogen or bromine, and R4means hydrogen.

9. The compound according to claim 1, where R1means optionally substituted phenyl(C1-C3)alkyl.

10. The connection according to claim 9, where R1means phenyl(C1-C3)alkyl, substituted groups CONR7aR7b, SO2NR8aR8bor C1-C6alkylsulfonyl, and optionally additionally substituted by one or two substituents selected from the group comprising (a) C1-C6alkyl, (b) C1-C6alkoxygroup, (C) halogen(C1 -C6)alkyl, (d) halogen(C1-C6)alkoxygroup, (e) carboxyl, (f) C1-C6alkoxycarbonyl, (h) cyano, (i) C1-C6allmenalp, (j) halogen, and (k) a nitro-group, and R5a, R5bmean CH3.

11. The connection according to claim 9, where R1means phenyl(C1-C3)alkyl, substituted in position 4 groups CONH2, SO2NH2or C1-C6alkylsulfonyl, and optionally additionally substituted by one or two substituents selected from the group comprising (a) C1-C6alkyl, (b) C1-C6alkoxygroup, (C) halogen(C1-C6)alkyl, (d) halogen(C1-C6)alkoxygroup, (e) carboxyl, (f) C1-C6alkoxycarbonyl, (h) cyano, (i) C1-C6allmenalp, (j) halogen, and (k) a nitro-group, and R5aand R5bmean CH3.

12. Connection to item 11, where R3means hydrogen or bromine, R4means hydrogen.

13. The compound according to claim 1, where R1means optionally substituted heteroaryl(C1-C3)alkyl or heteroaryl, R4, R7a, R7b, R8aand R8bmean hydrogen.

14. The compound according to claim 1, where R1means phenyl, substituted CR11aR11bCOR12where R11aand R11bmean hydrogen, and R12means1-C6alkoxygroup or NR7a/sup> R7b.

15. The compound according to claim 1 in free base form or pharmaceutically acceptable salt selected from the group including
4-[2-(1-benzylpiperidine-4-ylamino)pyrimidine-4-yloxy]for 3,5-dimethylbenzonitrile,
4-[2-(1-benzylpiperidine-4-ylamino)-5-bromopyrimidine-4-yloxy]for 3,5-dimethylbenzonitrile,
4-{2-[1-(4-methanesulfonylaminoethyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}benzoic acid, triptorelin,
4-[5-bromo-2-(1-pyridine-4-iletilerini-4-ylamino)pyrimidine-4-yloxy]for 3,5-dimethylbenzonitrile, triptorelin,
4-[5-bromo-2-(1-thiophene-2-iletilerini-4-ylamino)pyrimidine-4-yloxy]for 3,5-dimethylbenzonitrile, triptorelin,
4-[5-bromo-2-(1-thiophene-3-iletilerini-4-ylamino)pyrimidine-4-yloxy]for 3,5-dimethylbenzonitrile, triptorelin,
4-[5-bromo-2-(1-thiazol-2-iletilerini-4-ylamino)pyrimidine-4-yloxy]for 3,5-dimethylbenzonitrile, triptorelin,
4-{5-bromo-2-[1-(4-cyanobenzyl)piperidine-4-ylamino]pyrimidine-4-yloxy)for 3,5-dimethylbenzonitrile, triptorelin,
N-(4-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}phenyl)ndimethylacetamide, triptorelin,
4-{5-bromo-2-[1-(1H-pyrrol-2-ylmethyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile, triptorelin,
4-{5-bromo-2-[1-(3H-imidazol-4-ylmethyl)piperidine-4-ylamino]-pyrimidine-yloxy}is 3.5-dimethylbenzonitrile, triptorelin,
N-(3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}phenyl)ndimethylacetamide, triptorelin,
4-{5-bromo-2-[1-(3-terbisil)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile, triptorelin,
4-{5-bromo-2-[1-(3-nitrobenzyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile, triptorelin,
4-{5-bromo-2-[1-(4-methanesulfonylaminoethyl)piperidine-4-ylamino]-pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{5-bromo-2-[1-(2-chloro-4-methanesulfonylaminoethyl)piperidine-4-ylamino]-pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{5-bromo-2-[1-(4-nitrobenzyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile, triptorelin,
4-{5-bromo-2-[1-(2-cyanobenzyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,triptorelin,
4-{5-bromo-2-[1-(3-cyanobenzyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,triptorelin,
4-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}-3-chlorobenzenesulfonamide,
4-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}-3-chlorbenzene acid,
3-chloro-4-{4-[4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}benzosulfimide,
3-chloro-4-{4-[4-(2-chloro-4-cyano-6-methylphenoxy)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}benzosulfimide,
3-chloro-4-{4-[4-(2-chloro-4-cianfrocca)pyrimidine-2-ylamine is]piperidine-1-ylmethyl}benzosulfimide,
3-chloro-4-{4-[4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}benzamide,
4-{2-[1-(2-chloro-4-methanesulfonylaminoethyl)piperidine-4-ylamino]-pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}-3-chlorobenzamide,
4-{2-[1-(2-chloro-4-cyanobenzyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{5-bromo-2-[1-(2-chloro-4-cyanobenzyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{5-bromo-2-[1-(2,3-diferensial)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{5-bromo-2-[1-(3-chloropyridin-4-ylmethyl)piperidine-4-ylamino]-pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{2-[1-(3-chloropyridin-4-ylmethyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{5-bromo-2-[1-(4-tert-butylbenzyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{5-bromo-2-[1-(3-trifloromethyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4'-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}biphenyl-2-carbonitrile,
4-{5-bromo-2-[1-(4-cryptomaterial)piperidine-4-ylamino]-pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{5-bromo-2-[1-(3-cryptomaterial)piperidine-4-ylamino]-pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{5-bromo-2-[1-(3-Chlorobenzyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-DIMET benzonitrile
4-{5-bromo-2-[1-(4-Chlorobenzyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{2-[1-(2,4-bis-trifloromethyl)piperidine-4-ylamino]-5-bromopyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{5-bromo-2-[1-(3,5-dimethoxybenzyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-[5-bromo-2-(1-quinoline-8-iletilerini-4-ylamino)pyrimidine-4-yloxy]for 3,5-dimethylbenzonitrile,
4-{5-bromo-2-[1-(3-chloro-4-terbisil)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{2-[1-(3-chloropyridin-4-ylmethyl)piperidine-4-ylamino]pyrimidine-4-ylamino}is 3.5-dimethylbenzonitrile,
3-chloro-4-{(1R,5S)-3-[4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-8-azabicyclo[3.2.1]Oct-8-ylmethyl}benzamide,
4-{2-[(1R,5S)-8-(2-chloro-4-methanesulfonylaminoethyl)-8-azabicyclo[3.2.1]Oct-3-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
3-chloro-4-{2-[1-(2-chloro-4-methanesulfonylaminoethyl)piperidine-4-ylamino]-pyrimidine-4-yloxy}-5-methylbenzonitrile,
4-{5-bromo-2-[(1R,5S)-8-(2-chloro-4-methanesulfonylaminoethyl)-8-azabicyclo-[3.2.1]Oct-3-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{(1R,5S)-3-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-8-azabicyclo[3.2.1]Oct-8-ylmethyl}-3-chlorobenzamide,
4-{5-bromo-2-[1-(2-chloro-4-methanesulfonylaminoethyl)piperidine-4-ylamino]-pyrimidine-4-yloxy}-3-chloro-5-methylbenzonitrile,
isopropyl ester 4-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenylimino)-pyrimidine-2-ylamino]piperidine-1-ILM is Tyl}-3-chlorbenzoyl acid,
3-chloro-4-{4-[4-(2-chloro-4-cyano-6-methylphenoxy)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}benzamide,
4-[5-bromo-2-(1-pyrimidine-4-iletilerini-4-ylamino)pyrimidine-4-yloxy]for 3,5-dimethylbenzonitrile,
4-{2-[1-(2-chloro-4-methanesulfonylaminoethyl)piperidine-4-ylamino]-5-cryptomaterial-4-yloxy}is 3.5-dimethylbenzonitrile,
4-[2-(8-benzyl-8-azabicyclo[3.2.1]Oct-3-ylamino)-5-bromopyrimidine-4-yloxy]for 3,5-dimethylbenzonitrile,
4-{2-[1-(2-chloro-4-methanesulfonylaminoethyl)piperidine-4-ylamino]-5-ftorpirimidinu-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{5-chloro-2-[1-(2-chloro-4-methanesulfonylaminoethyl)piperidine-4-ylamino]-pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{4-[5-bromo-4-(2-chloro-4-cyano-6-methylphenoxy)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}-3-chlorobenzamide,
4-{4-[5-bromo-4-(2-chloro-4-cyano-6-methylphenoxy)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}-3-chlorobenzenesulfonamide,
4-{5-bromo-2-[1-(1-phenylethyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{5-bromo-2-[1-(1-oxypyridine-4-ylmethyl)piperidine-4-ylamino]-pyrimidine-4-yloxy}-3-chloro-5-methylbenzonitrile,
4-{4-[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}-3-chlorobenzenesulfonamide,
4-{4-[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]piperidine-1-ylmethyl}-3-chlorobenzamide,
4-{6-amino-5-bromo-2-[1-(2-chloro-4-methanesulfonylaminoethyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzoic the sludge
4-{2-[1-(2-chloro-4-methanesulfonylaminoethyl)piperidine-4-ylamino]-pyrimidine-4-ylamino}is 3.5-dimethylbenzonitrile,
3-chloro-4-{4-[4-(4-cyano-2,6-dimethylphenylimino)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}benzosulfimide,
5-bromo-N4-(4-bromo-2,6-dimetilfenil)N2-[1-(2-chloro-4-methanesulfonyl-benzyl)piperidine-4-yl]pyrimidine-2,4-diamine,
4-{4-[4-(4-bromo-2,6-dimethylphenylimino)pyrimidine-2-ylamino]piperidine-1-ylmethyl}-3-chlorobenzenesulfonamide,
4-{5-bromo-2-[1-(2-chloro-4-methanesulfonylaminoethyl)piperidine-4-ylamino]-pyrimidine-4-ylamino}is 3.5-dimethylbenzonitrile,
3-chloro-4-{4-[4-(4-cyano-2,6-dimethylphenylimino)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}benzamide,
4-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenylimino)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}-3-chlorobenzamide,
N4-(4-bromo-2,6-dimetilfenil)N2-[1-(2-chloro-4-methanesulfonylaminoethyl)-piperidine-4-yl]pyrimidine-2,4-diamine,
(E)-3-(4-{2-[1-(2-chloro-4-methanesulfonylaminoethyl)piperidine-4-ylamino]-pyrimidine-4-ylamino}is 3.5-dimetilfenil)Acrylonitrile,
3-chloro-4-(4-{4-[4-((E)-2-cyanovinyl)-2,6-dimethylphenylamine]pyrimidine-2-ylamino}piperidine-1-ylmethyl)benzamide,
4-{5-bromo-2-[1-(3-chloropyridin-4-ylmethyl)piperidine-4-ylamino]-pyrimidine-4-ylamino}is 3.5-dimethylbenzonitrile,
4-{2-[(1R,5S)-8-(2-chloro-4-methanesulfonylaminoethyl)-8-azabicyclo[3.2.1]Oct-3-ylamino]pyrimidine-4-ylamino}is 3.5-dimethylbenzonitrile,
isopropyl ether 3-chloro-4-{4-[4-(4-cyano-2,6-dimethylphenylimino)pyrimidine-2-ylamino]piperidine-1-ylmethyl}benzoic acid,
3-chloro-4-{4-[4-(4-cyano-2,6-dimethylphenylimino)pyrimidine-2-ylamino]piperidine-1-ylmethyl}benzoic acid,
4-{5-bromo-2-[1-(2-chloro-4-methanesulfonylaminoethyl)piperidine-4-ylamino]pyrimidine-4-ylamino}-3-chloro-5-methylbenzonitrile,
(E)-3-(4-{5-bromo-2-[1-(2-chloro-4-methanesulfonylaminoethyl)piperidine-4-ylamino]pyrimidine-4-ylamino}is 3.5-dimetilfenil)Acrylonitrile,
4-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenylimino)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}-3-chlorbenzene acid,
3-chloro-4-{4-[4-(4-cyano-2-methylphenylimino)pyrimidine-2-ylamino]-piperidine-1-ylmethyl)benzosulfimide,
4-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenylimino)pyrimidine-2-ylamino]-piperidine-1-ylmethyl}-3-chloro-N-(2-dimethylaminoethyl)benzamide,
4-{4-[4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]piperidine-1-yl}benzosulfimide,
3-{4-[4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]piperidine-1-yl}benzosulfimide,
4-{6-amino-2-[1-(3-cyanophenyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{5-bromo-2-[1-(3-cyanophenyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{2-[1-(3-cyanophenyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
3-{4-[4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]piperidine-1-yl}benzamide,
3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}benzamide,
4-{5-bromo-2-[1-(3-methanesulfonyl)piperidine-4-ylamino]-pyrimidine-4-ILO is si}is 3.5-dimethylbenzonitrile,
3-chloro-4-{2-[1-(3-methanesulfonyl)piperidine-4-ylamino]pyrimidine-4-yloxy}-5-methylbenzonitrile,
4-{5-bromo-2-[1-(3-methanesulfonyl)piperidine-4-ylamino]-pyrimidine-4-yloxy}-3-chloro-5-methylbenzonitrile,
3-{4-[5-bromo-4-(2-chloro-4-cyano-6-methylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}benzamide,
3-{4-[4-(2-chloro-4-cyano-6-methylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}benzamide,
3-{4-[4-(4-cyano-2,6-dimethylphenoxy)-5-ftorpirimidinu-2-ylamino]-piperidine-1-yl}benzamide,
4-[5-bromo-2-(1-pyrimidine-5-reparacin-4-ylamino)pyrimidine-4-ylamino]for 3,5-dimethylbenzonitrile,
3-{4-[5-chloro-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}benzamide,
3-{4-[4-(4-cyano-2,6-dimethylphenoxy)-5-cryptomaterial-2-ylamino]piperidine-1-yl}benzamide,
3,5-dimethyl-4-{2-[1-(3-nitrophenyl)piperidine-4-ylamino]pyrimidine-4-yloxy}benzonitrile,
4-{5-fluoro-2-[1-(3-methanesulfonyl)piperidine-4-ylamino]-pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{5-chloro-2-[1-(3-methanesulfonyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{2-[1-(3-methanesulfonyl)piperidine-4-ylamino]-5-trifluoromethyl-pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{5-bromo-2-[1-(3-chloro-5-cyanophenyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
4-{2-[1-(3-chloro-5-cyanophenyl)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
3-{4-[5-bromo-4-(4-cyano-2,6-dimethylpyrimidin-2-ylamino]-piperidine-1-yl}-5-chlorobenzamide,
3-chloro-5-{4-[4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}benzamide,
2-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}benzamide,
4-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}benzamide,
3-chloro-5-methyl-4-[2-(3,4,5,6-tetrahydro-2H-[1,3']bipyridinyl-4-ylamino)-pyrimidine-4-yloxy]benzonitrile,
3-chloro-5-methyl-4-[2-(1-pyrimidine-2-reparacin-4-ylamino)pyrimidine-4-yloxy]benzonitrile,
3-chloro-4-{2-[1-(3-cyanomethyl)piperidine-4-ylamino]pyrimidine-4-yloxy}-5-methylbenzonitrile,
4-{2-[1-(3-AMINOPHENYL)piperidine-4-ylamino]-5-bromopyrimidine-4-yloxy}-3-chloro-5-methylbenzonitrile,
3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}-N-methylbenzamide,
3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}-N-cyclopropylbenzene,
3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}-N-(2-hydroxyethyl)benzamide,
3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}-N-(2-dimethylaminoethyl)benzamide,
2-(3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}phenyl)acetamide", she
4-{5-bromo-2-[1-(3-hydroxymethylene)piperidine-4-ylamino]pyrimidine-4-yloxy}is 3.5-dimethylbenzonitrile,
N-(3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}phenyl)methanesulfonamide,
N-(3-{4-[5-bromo-4-(4-cyano-2,6-d is methylphenoxy)pyrimidine-2-ylamino]piperidine-1-yl}phenyl)acetamide", she
3-{4-[5-bromo-4-(4-cyano-2-methoxy-6-methylphenoxy)pyrimidine-2-ylamino]piperidine-1-yl}benzamide,
2-(3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}phenyl)-N-(2-dimethylaminoethyl)ndimethylacetamide,
(3-{4-[5-bromo-4-(2-chloro-4-cyano-6-methylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}phenyl)acetic acid,
2-(3-{4-[5-bromo-4-(2-chloro-4-cyano-6-methylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}phenyl)-N-(2-hydroxy-1-methylethyl)ndimethylacetamide,
4-(5-bromo-2-{1-[3-(1,2-dihydroxyethyl)phenyl]piperidine-4-ylamino}-pyrimidine-4-yloxy)for 3,5-dimethylbenzonitrile,
3-{4-[4-(4-cyano-2,6-dimethylphenoxy)-5-methylpyrimidin-2-ylamino]-piperidine-1-yl}benzamide,
2-(3-{4-[4-(2-chloro-4-cyano-6-methylphenoxy)-5-methylpyrimidin-2-ylamino]piperidine-1-yl}phenyl)acetamide", she
3-{4-[5-bromo-4-(4-cyano-2-fluoro-6-methylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}benzamide,
N-[2-(3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}phenyl)acetyl]methanesulfonamide,
3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}benzosulfimide,
2-(3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}phenyl)-3-hydroxypropionic acid,
2-(3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}phenyl)propionic acid,
(3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}phenyl)metacercaria acid,
(3-{4-[5-the rum-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}phenyl)hydroxyestra acid,
(3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}phenyl)DIPEROXY acid,
(3-{4-[5-chloro-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-piperidine-1-yl}phenyl)metacercaria acid,
(3-{4-[4-(4-cyano-2,6-dimethylphenoxy)-5-methylpyrimidin-2-ylamino]-piperidine-1-yl}phenyl)metacercaria acid,
amide 4-[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4'-carboxylic acid,
amide 4-[4-(4-cyano-2,6-dimethylphenoxy)pyrimidine-2-ylamino]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-6'-carboxylic acid,
4-{5-bromo-2-[1-(3-cyanophenyl)piperidine-4-ylamino]pyrimidine-4-ylamino}is 3.5-dimethylbenzonitrile,
3-{4-[4-(4-cyano-2,6-dimethylphenylimino)pyrimidine-2-ylamino]-piperidine-1-yl}benzamide,
3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenylimino)pyrimidine-2-ylamino]-piperidine-1-yl}benzamide,
N4-(4-bromo-2,6-dimetilfenil)N2-[1-(3-methanesulfonyl)piperidine-4-yl]pyrimidine-2,4-diamine,
3-(4-{4-[4-((E)-2-cyanovinyl)-2,6-dimethylphenylamine]pyrimidine-2-ylamino}piperidine-1-yl)benzamid,
3-(4-{4-[2-chloro-4-((E)-2-cyanovinyl)-6-methylphenylimino]pyrimidine-2-ylamino}piperidine-1-yl)benzamid,
3-{4-[4-(2-chloro-4-cyano-6-methylphenylimino)pyrimidine-2-ylamino]-piperidine-1-yl}benzamide,
methyl ester of 4-[4-(4-cyano-2,6-dimethylphenylimino)pyrimidine-2-ylamino]-3,4,5,6-tetrahydro-2H-[1,3']bipyridinyl-5'-carboxylic acid,
4-[4-(4-cyano-2,6-di is ethylvanillin)pyrimidine-2-ylamino]-3,4,5,6-tetrahydro-2H-[1,3']bipyridinyl-5'-carboxylic acid,
3,5-dimethyl-4-[2-(3,4,5,6-tetrahydro-2H-[1,3']bipyridinyl-4-ylamino)-pyrimidine-4-ylamino]benzonitrile,
3,5-dimethyl-4-[2-(1-pyrimidine-2-reparacin-4-ylamino)pyrimidine-4-ylamino]benzonitrile,
4-[5-bromo-2-(1-pyrimidine-2-reparacin-4-ylamino)pyrimidine-4-ylamino]for 3,5-dimethylbenzonitrile,
4-{5-amino-2-[1-(3-AMINOPHENYL)piperidine-4-ylamino]pyrimidine-4-ylamino}is 3.5-dimethylbenzonitrile,
4-{2-[1-(3-cyanomethyl)piperidine-4-ylamino]pyrimidine-4-ylamino}is 3.5-dimethylbenzonitrile,
3-{4-[5-bromo-4-(2-chloro-4-cyano-6-forgenerating)pyrimidine-2-ylamino]piperidine-1-yl}benzamide, and
2-(3-{4-[5-bromo-4-(4-cyano-2,6-dimethylphenylimino)pyrimidine-2-ylamino]piperidine-1-yl}phenyl)-N,N-dimethylacetamide.

16. The compound of formula I according to any one of claims 1 to 15 for use as a medicinal product, which has antiviral activity against HIV.

17. Pharmaceutical composition having activity against reverse transcriptase of HIV, comprising the compound according to any one of claims 1 to 15 in a therapeutically effective amount and at least one carrier, excipient or diluent.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to di(arylamino)aryl derivatives presented in the patent claim. The compounds show an inhibitory effect on protein EML4-ALK v1 and protein EGFR kinase activity. Also the invention refers to a pharmaceutical composition containing said compounds, the hybrid protein EML4-ALK and mutant protein EGFR kinase activity inhibitor, the use of said compounds for preparing the pharmaceutical composition, and to a method of preventing or treating non-small-cell lung cancer or EML4-ALK hybrid polynucleotide-positive and/or mutant EGFR polynucleotide-positive non-small-cell lung cancer.

EFFECT: use of di(arylamino)aryl as the protein EML4-ALK v1 and protein EGFR kinase activity inhibitors.

12 cl, 95 tbl, 55 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to aryl- and heteroarylsubstituted diasaspiropyridine derivatives of formula (I) to its pharmaceutically acceptable acid- or base-additive salt wherein A represents a radical of formula (II) wherein each k, l, m, n independently represents an integer equal to 0, 1, 2, 3 or 4, provided (k+1) and (m+n) are equal to 2, 3, 4 or 5; wherein one of -CH2-fragments can be substituted by atom O; and wherein one of -CH2-fragments can be substituted by an oxo group; X represents CH or N; R3 is specified in a group consisting of hydrogen, C1-5alkyl and C3-6cycloalkyl; each R4, R5 is independently specified in a group including hydrogen, halogen, oxo, C1-3alkyl and C1-3alkyloxy; p represents an integer equal to zero, 1, 2 or 3; q represents an integer equal to zero, 1, 2 or 3; each Y1, Y3, is independently specified in a group including a single bond and O; Y2 represents saturated or unsaturated C1-6hydrocarbon radical with a straight chain; B is specified in a group including phenyl optionally substituted by the number of the substitutes R6 each of which is independently specified in halogen; and wherein r represents an integer equal to zero, 1 or 2; alkyl represents a saturated hydrocarbon radical with a straight and branched chain containing said number of carbon atoms; wherein said radical can be optionally substituted by one or more carbon atoms or more radicals specified in a group including halogen, cyano, hydroxy, amino, oxo, carboxyl, nitro, thio and formyl; and halogen represents fluorine, chlorine, bromine or iodine. Also, the invention refers to a pharmaceutical composition based on the compounds of formula I as an active ingredient for preparing a drug for preventing and/or treating mental disorders, including but not limited to anxiety, eating behavior disorder, affective disorders, such as bipolar disorders and depression, psychosis, such as schizophrenia, and sleeping disorders; obesity, diabetes; sexual disorders and neurological disorders; to a method for preparing a pharmaceutical composition, and to using the compounds of formula I for preparing the drug.

EFFECT: there are prepared and described new compounds possessing melanin-concentrating hormone (MCH), particularly MCH-1 antagonist activity.

19 cl, 4 ex, 7 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to novel derivatives of spiro{indeno[1,2-6]quinoline-6,3'-pyrroles} of formula where R=CH2Ph, Ph; X=H, Me, OMe. The invention also relates to a method for synthesis of the said compounds.

EFFECT: novel compounds, having analgesic activity, which can be used for synthesis of novel heterocyclic compounds, are obtained.

4 cl, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of diazepane of formula , where A, X, R3, R4, R5, R6, R8, R9, R10, R11, R12, R13, n and m have values, given in description and formula of invention, as well as their physiologically acceptable salts. Said compounds are antagonists of chemokine receptors CCR-2, CCR-5 and/or CCR-3 receptor and can be used in medicine as medications.

EFFECT: obtaining novel diazepane derivatives.

20 cl, 505 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula in which R1 denotes a) adamantyl, hydroxyadamantyl or trifluoromethylphenyl; R2 denotes hydrogen, methyl, ethyl or cyclopropyl; one of R3 and R4 denotes alkyl, cycloalkyl, haloalkyl or is absent, and the other denotes a) hydrogen, alkyl, pyridinyl, cycloalkyl, cycloalkylalkyl or haloalkyl; b) phenyl or phenyl substituted with one to three substitutes independently selected from fluorine, chlorine, bromine, haloalkyl and alkoxy group; c) phenylalkyl, where the phenylalkyl is optionally substituted with one to three halogens; e) naphthyl or tetrahydronaphthyl; f) phenylalkoxyalkyl; g) hydroxyalkyl; or h) pyridinyloxyalkyl or pyridinyloxyalkyl substituted with an cyano group; or R3 and R4 together with a carbon atom with which they are bonded form a cycloalkane or piperdine, where the cycloalkyl and piperidine are optionally substituted with one to three substitutes independently selected from aryl and arylalkyl; one of R5 and R6 denotes hydrogen, isopropyl, isobutyl or haloalkyl, and the other denotes hydrogen or is absent; and to pharmaceutically acceptable salts thereof, under the condition that 1,3-dihydro-4-phenyl-1-(3-(trifluoromethyl)phenyl)-2H-imidazol-2-one is excluded, and if one of R3 and R4 denotes methyl, ethyl, n-propyl or n-butyl, and the other denotes hydrogen or is absent, then R2 denote hydrogen or methyl. The invention also relates to a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds, having 11-beta-hydroxysteroid dehydrogenase 1 (11-beta-HSDI) inhibiting activity.

15 cl, 257 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula: where X is selected from a group consisting of hydrogen, halogen, cyano, nitro, ethenyl, cyclopropyl, methyl, ethyl, isopropyl, methoxy and vinyl; Y denotes hydrogen or fluorine; R4 and R5 denote hydrogen or lower alkyl; one of R1 and R8 is selected from a group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, cycloalkyl, substituted cycloalkyl, cycloalkenyl and substituted cycloalkenyl, and the other denotes hydrogen; one of R6 and R7 is selected from a group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, cycloalkyl, substituted cycloalkyl, cycloalkenyl and substituted cycloalkenyl, and the other denotes hydrogen, cyano group or lower alkyl; R2 is selected from a group consisting of hydrogen, lower alkyl and substituted lower alkyl; R3 is selected from a group consisting of oxygen, sulphur and NNH(C=O)OR9; R9 denotes lower alkyl or substituted lower alkyl; where the term "substituted" denotes substitution with 1-5 substitutes independently selected from a group consisting of lower alkyl, lower alkenyl, lower alkynyl, dioxo-lower alkenyl, halogen, hydroxy, -CN, -CF3, -NH2, -N(H, lower alkyl), N(lower alkyl)2, aminocarbonyl, carboxy, -NO2, lower alkoxy, thio-lower alkoxy, lower alkylsulphonyl, aminosulphonyl, lower alkylcarbonyl, lower alkylcarbonyloxy, lower alkoxycarbonyl, lower alkylcarbonyl-NH, fluoro-lower alkyl, fluoro-lower alkoxy, lower alkoxy-carbonyl-lower alkoxy, carboxy-lower alkoxy, carbamoyl-lower alkoxy, hydroxy-lower alkoxy, -NH2-lower alkoxy, -N(H, lower alkyl)-lower alkoxy, -N(lower alkyl)2-lower alkoxy, benzyloxy-lower alkoxy, mono or di-lower alkyl, substituted with aminosulphonyl or lower alkyl, which can optionally be substituted with a halogen, hydroxy, -NH2, -N(H, lower alkyl) or -N(lower alkyl)2; the term "heteroaryl" denotes an aromatic heterocyclic ring system containing up to two rings; and the term "heterocycle" denotes a substituted or unsubstituted 5-8-member mono- or bicyclic, aromatic or non-aromatic hydrocarbon, where 1-3 carbon atoms are replaced with a heteroatom selected from a nitrogen, oxygen or sulphur atom; and pharmaceutically acceptable salts thereof or esters. The invention also relates to a pharmaceutical composition, use of compounds in claims 1-31, as well as to methods of producing compounds of formulae II and III.

EFFECT: obtaining novel biologically active compounds which inhibit interaction of MDM2 protein with a p53-like peptide.

38 cl, 186 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel cyclic N,N'-diarylthioureas or N,N'-diarylureas of general formula (1), their optic (R)- and (S)-isomers and their pharmaceutically acceptable salts - antagonists of androgenic receptors. In formula (1), where: X represents oxygen or sulfur atom; m=0 or 1, mR1 represents C1-C3alkyl; R2 and R3 represent hydrogen atom; or R2 and R3 together with carbon atom, to which they are bound, form group C=O; or represents group NH; R4 and R5 represent hydrogen atom; or R4 represents hydrogen atom, and R5 represents methyl; or R4 represents hydrogen atom, methyl, and R5 represents group Zn-Y-R6, in which n=1 or 2, Z represents CH2 or C=0 and Y- oxygen atom or N-CH3, or Y represents C=O, and Z represents CH2; R6 represents hydrogen atom, methyl, benzyl, hydroxygroup or R5 and R4 together with atoms, to which they are bound, form five or sic-member heterocycle, including, at least, oxygen or nitrogen atom, which can be substituted by methyl. Invention also relates to method of obtaining compounds.

EFFECT: invention relates to anti-cancer substance, pharmaceutical composition, medication and method of treating prostate cancer with application of invention compounds.

12 cl, 6 dwg, 16 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to novel derivatives of quinolone or one pharmaceutically acceptable salts thereof, solvates thereof or solvates of salts thereof, having general formula I , in which R1 denotes fluorine, R3 denotes halogen, a hydroxy group or a C1-C4-alkoxy group, R4 denotes C1-C6-alkyl or C3-C8-cycloalkyl, where the alkyl can contain 1-3 substitutes, and the substitutes are independently selected from a group comprising halogen or trifluoromethyl, and where the cycloalkyl can contain 1-3 halogen atoms as substitutes, or R3 and R4 together with atoms to which they are bonded form a ring with a group of formula , in which * indicates a site for bonding with a carbon atom, and # indicates a site for bonding with a nitrogen atom, R7 and R8 independently denote halogen, trifluoromethyl, a monofluoromethoxy group, a difluoromethoxy group, a trifluoromethoxy group, C1-C3-alkyl or C1-C3-alkoxy group, and R9 denotes hydrogen, halogen or C1-C3-alkyl, or R8 denotes a trifluoromethoxy group, and R7 and R9 denote hydrogen, R10 denotes a group of formula or , in which * indicates a site for bonding with a carbon atom, R2 is bonded in position 3 or 4 and denotes a hydroxy group, hydroxycarbonyl, aminocarbonyl, C1-C4-alkyl, C1-C4-alkoxycarbonyl, C3-C6-cycloalkylcarbonyl or optionally hydroxy-substituted C1-C6-alkylaminocarbonyl, where the alkyl is substituted with one substitute and the substitute is selected from a group comprising a hydroxy group, hydroxycarbonyl, aminocarbonyl, C1-C4-alkoxycarbonyl and 2-oxopyrrolidin-1-yl, R5 and R6 are independently bonded in positions 3, 4 or 5 and independently denote hydrogen, hydroxy group, methyl or ethyl, and Y denotes a methylene group or an oxygen atom. The invention also relates to methods of producing a compound of formula I, a medicinal agent based on the compound of formula I, use of the compound of formula I and a method of fighting viral infections.

EFFECT: novel substituted quinolone derivatives which are useful in treating viral diseases are obtained.

11 cl, 1 tbl, 69 ex

FIELD: medicine.

SUBSTANCE: invention refers to indole-3-yl-carbonyl-spiro-piperidine derivatives which have an effect of Vla-receptor antagonists and are presented by Formula I: where a tail spiropiperidine group A and residual R1, R2 and R3 are such as specified in the patent claim.

EFFECT: higher efficiency of applying the compounds in drugs effective in dysmenorrhea, hypertension, chronic heart failure, inadequate vasopressin secretion, hepatic cirrhosis, nephrotic syndrome, obsessive-compulsive disorder, anxious and depressive disorders.

22 cl, 42 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel indol-3-yl-carbonyl-asaspiro-derivatives of formula I: where R1 represents H,-(CH2)m-Ra, where Ra represents NRiRii, phenyl, possibly substituted by one or more than one B, -(CH2)n-(CO)-Rb , where Rb represents NRiRii; there exists one or more than one R2 , where each R2 is the same or different and represents one or more than one H, in halogen way; R3 represents H, C1-6-alkyl; B represents in halogen way; Ri and Rii each independently represents H, C1-6-alkyl, C1-6alkyl-NRiiiRiv; Riii and Riv each independently represents C1-6alkyl; m equals 1-6; n equals 1-4; A represents group : where R4 represents H or C1-6alkyl; R5 represents phenyl, possibly substituted in halogen way; or its pharmaceutically acceptable salt; on condition that 1-(1H-indol-3-yl-carbonyl)-4-(1,3-dioxolan-2-yl)pyperidine is excluded.

EFFECT: compounds demonstrate antagonistic activity with respect to Via vasopressin receptor, which makes it possible to apply them for obtaining pharmaceutical composition.

22 cl, 4 dwg, 16 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to dihydropyrazolone derivatives or of formula (I), where R1 denotes a heteroaryl group of formulae given below, where * denotes the linkage point with the dihydropyrazolone ring, A in each individual occurrence denotes C-R4 or N, wherein at most two ring members A represent N at the same time, E denotes O or S, R2, R3 and R4 are as defined in the claim. The invention also relates to a method of producing said compounds.

EFFECT: compounds of formula (I) inhibit HIF-propylhydroxylase activity and can be used to treat and/or prevent diseases, as well as for producing medicaments for treating and/or preventing diseases, particularly cardiovascular and haematologic diseases, kidney diseases, and for promoting the healing of wounds.

10 cl, 10 tbl, 178 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel dihydroindolone derivatives of formula I or its pharmaceutically acceptable salts: Formula I, where values of R1-R9,R16,R17,n1,n2,n3, m, are given in 1 of the formula. Described are methods of obtaining compounds.

EFFECT: compounds demonstrate anti-tumour activity, which makes it possible to use them in pharmaceutical compositions for treatment and/or prevention of diseases, associated with protein tyrosine kinases in organism, in particular for treatment and/or prevention of tumours and diseases, associated with proliferation of fibroblasts.

13 cl, 1 dwg, 5 tbl, 37 ex

FIELD: medicine.

SUBSTANCE: described are novel heterocyclic compounds of general formulae and (values of radicals are given in invention formula), pharmaceutical compositions containing them and application of said heterocyclic compounds for treatment disorders mediated with MAP kinase cascade.

EFFECT: increase of compound efficiency.

67 cl, 106 ex, 2 tbl, 2 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted pyrimidine derivatives having PGDS inhibiting properties. In formula (I): (I), R1 denotes phenyl or a 5- or 6-member heteroaryl containing 1-3 heteroatoms selected from N, O and S, each optionally having one or more of the following independent substitutes: halogen, (C1-C6)-alkyl, or (C1-C4)-haloalkyl; R2 denotes hydrogen or (C1-C6)-alkyl, which is optionally substituted with one or more halogens; R3 denotes hydrogen, (C1-C6)-alkyl or phenyl; R4 denotes C6-cycloalkyl, phenyl, a 6-member heterocyclyl containing one N heteroatom, a 6-member heteroaryl containing one N heteroatom, -C(=O)-NY1Y2, -C(=S)-NY1Y2, or -C(=O)-R5, where the phenyl, 6-member heteroaryl or 6-member heterocyclyl group optionally has one or more independent substitutes R6, or R3 and R4 together with a nitrogen atom with which they are bonded form a 5- or 6-member heterocyclyl containing one or two heteroatoms selected from N, O and S, a 6-member heterocyclenyl containing two or three N heteroatoms, a 5-member monocyclic or 9-member bicyclic heteroaryl containing one to three N heteroatoms, phenylheterocyclyl, where the heterocyclyl is 5- or 6-membered and contains one or two heteroatoms selected from N and O, each optionally having one or more independent substitutes R6. Values of R5, R6, Y1, Y2 are given in the claim. The invention also relates to a pharmaceutical composition containing said compounds.

EFFECT: improved method.

15 cl, 227 ex

FIELD: medicine.

SUBSTANCE: invention refers to the new compound 5-chlor-N2-[(1S)-1-(5-flouropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine or its pharmaceutically acceptable salt possessing the properties of a tyrosine kinase inhibitor, particularly JAK-kinase. The invention also refers to a based pharmaceutical composition.

EFFECT: compound may be used for treating cancer.

5 cl, 5 dwg, 37 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to di(arylamino)aryl derivatives presented in the patent claim. The compounds show an inhibitory effect on protein EML4-ALK v1 and protein EGFR kinase activity. Also the invention refers to a pharmaceutical composition containing said compounds, the hybrid protein EML4-ALK and mutant protein EGFR kinase activity inhibitor, the use of said compounds for preparing the pharmaceutical composition, and to a method of preventing or treating non-small-cell lung cancer or EML4-ALK hybrid polynucleotide-positive and/or mutant EGFR polynucleotide-positive non-small-cell lung cancer.

EFFECT: use of di(arylamino)aryl as the protein EML4-ALK v1 and protein EGFR kinase activity inhibitors.

12 cl, 95 tbl, 55 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to heterocyclic compounds of formula (I), where R1 represents C1-6 alkyl, optionally substituted with hydroxy, monocyclic C3-8 cycloaliphatic radical, optionally substituted with hydroxy, or phenyl; R2 represents H, C1-6 alkyl, optionally substituted with hydroxy or morpholine, monocyclic C3-8 cycloaliphatic radical, optionally substituted with a hydroxy group or a heterocycloaliphatic radical, where the heterocycloaliphatic radical is piperidine, pyrrolidine or morpholine; each of a, a', b and c independently represents N or C(R3); each of R3, R5 and R6 independently represents H, halogen, phenyl, substituted with one substitute selected from methoxy methyl, amino, methoxy or trifluoromethoxy, or heteroaryl substituted with alkyl, hydroxy or alkoxy; R4 represents H; K represents -N(RX')-; J represents a bond, -O, alkylene, -C(O)-, -C(O)-O-, or -C(O)-N(Rx')-; RX' represents H; n equals 0; and under the condition that if R1 represents an unsubstituted alkyl, J represents -O-, then R2 represents H. The invention also relates to a pharmaceutical composition based on a compound of formula (I).

EFFECT: obtaining novel heterocyclic compounds, useful as modulators of interleukin receptor-associated kinase IRAK.

20 cl, 18 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are produced new diazepane substituted compounds representing various heterocyclic systems, including condensed, pharmaceutical compositions containing said compounds.

EFFECT: producing the compounds and compositions for preventing and treating neurological and mental disorders and diseases with involved orexin receptors.

13 cl, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula 1 and salts thereof, fungicidal compositions based on said compounds, a plant disease control method using compounds of formula , as well as intermediate compounds of formulae and . Values of radicals are given in the description.

EFFECT: high efficiency of the compounds.

14 cl, 20 dwg, 284 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I),

, where groups and radicals R1, R2 independently denote H, C1-8-alkyl or C3-7-cycloalkyl, where the alkyl or cycloalkyl group can be mono- or poly-substituted with identical or different groups R11; or R2 denotes a -CH2- or -CH2-CH2- bridge which is bonded with a group Y, and R1 is as defined above, or denotes a group selected from C1-4-alkyl-CO-, C1-4-alkyl-O-CO-, (C1-4-alkyl)NH-CO- or (C1-4-alkyl)2N-CO-, where the alkyl groups can be mono- or polyfluorinated; or R1 and R2 form an alkylene bridge such that R1R2N- denotes a group selected from: azetidine, pyrrolidine, piperdine, azepan, 2,5-dihydro-1H-pyrrole, 1,2,3,6-tetrahydropyridine, 2,3,4,7-tetrahydro-1H-azepine, 2,3,6,7-tetrahydro-1H-azepine, piperazine, in which the free amino group is substituted with R13, piperidin-4-one, morpholine, thiomorpholine, 4-C1-4-alkoxy iminopiperidin-1-yl and 4-hydroxy iminopiperidin-1-yl. Wherein, when R1 and R2 form an alkylene bridge, one or more H atoms in the alkylene bridge can be substituted with identical or different groups R14, and X denotes a C1-3-alkylene bridge which can contain one, two or three identical or different C1-3-alkyl substitutes; and Y denotes a group of subformula selected from: and , where the group can be mono-substituted with a substitute R20; Z denotes -CH2-CH2- or -C(=O)-CH2-; U, V both denote CH, one of groups U, V denotes N, and the other of U, V denotes CH, where CH can be substituted with L; and L independently denotes halogen, cyano or C1-3-alkyl; and k equals 0, 1 or 2; W is selected from a group consisting of -CH2-O- and -O-CH2-; B is selected from a group consisting of phenyl, pyridyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, furyl, thiophenyl and thiazolyl; each of which can be mono- or poly-substituted with identical or different substitutes R20; radicals R11, R13, R14, R20 assume values given in claim 1. The invention also relates to a pharmaceutical composition containing at least one compound of formula I and having action on MCH receptor.

EFFECT: disclosed pharmaceutical compositions are useful in treating metabolic disorders or eating disorders, especially obesity, bulimia, anorexia, hyperphagia and diabetes.

FIELD: medicine.

SUBSTANCE: invention refers to a deuterium-enriched α-ketoamide compound of formula wherein: D means a deuterium atom; the values R1-R5 are presented in cl.1 of the patent claim, and to a based pharmaceutical composition.

EFFECT: method improvement.

32 cl, 3 ex

Up!