Compounds useful for treating aids

Patent metadata

Field	Value
Publication number	US-9908869-B2
Application number	US-201414256334-A
Country	US
Kind code	B2
Filing date	Apr 18, 2014
Priority date	Jun 12, 2009
Publication date	Mar 6, 2018
Grant date	Mar 6, 2018

Abstract

A compound having the following formula or a pharmaceutically acceptable salt thereof:

where:
R″ is a hydrogen atom or a (C 1 -C 4 )alkyl group; n′ is 1 or 2; n is 1, 2, or 3; R independently represents a hydrogen atom, a halogen atom, or a group selected from a (C 1 -C 3 )alkyl group, a —CN group, a hydroxyl group, a —NR 1 R 2 group, a —COOR 1 group, a (C 1 -C 3 )fluoroalkyl group, a —NO 2 group, a (C 1 -C 3 )fluoroalkoxy, and a (C 1 -C 4 )alkoxy group; R′ is a hydrogen atom, a halogen atom, or a group selected from a (C 1 -C 3 )alkyl group, a —COOR1 group, a —NO 2 group, a —NR 1 R 2 group, a (C 1 -C 4 )alkoxy group, and a CN group; R 1 and R 2 are a hydrogen atom or a (C 1 -C 3 )alkyl group;

with the proviso that when R and R′ are not simultaneously a hydrogen atom:
when n is 1, R is not a methyl group in an ortho or para position with respect to N, when R′ is a hydrogen atom, R is not a bromine atom or a chlorine atom, and when R is a hydrogen atom, R′ is not a methyl or ethyl group, a —COOH group, a —COOC 2 H 5 group, or a bromine atom that is in an ortho position of the bond linked to NR″.

First claim

The invention claimed is:

1. A compound having the following formula or a pharmaceutically acceptable salt thereof:

where:
R″ is a hydrogen atom or a (C 1 -C 4 )alkyl group;
n′ is 1;
n is 1, 2, or 3;
R independently represents a hydrogen atom, a halogen atom, or a group selected from a (C 1 -C 3 )alkyl group, a —CN group, a hydroxyl group, a —NR 1 R 2 group, a —COOR 1 group, a (C 1 -C 3 )fluoroalkyl group, a —NO 2 group, a (C 1 -C 3 )fluoroalkoxy, and a (C 1 -C 4 )alkoxy group;
R′ independently represents a hydrogen atom, a halogen atom, or a group selected from a (C 1 -C 3 )alkyl group, a —COOR 1 group, a —NR 1 R 2 group, a (C 1 -C 4 )alkoxy group, and a CN group; and
R 1 and R 2 are independently a hydrogen atom or a (C 1 -C 3 )alkyl group;

with the provisos that:
R and R′ are not simultaneously a hydrogen atom,
when n is 1, R is not a methyl group in an ortho or para position with respect to N,
when R′ is a hydrogen atom, R is not a bromine atom or a chlorine atom, and
when R is a hydrogen atom, R′ is not a methyl or ethyl group, a —COOH group, a —COOC 2 H 5 group, or a bromine atom that is in an ortho position of the bond linked to NR″.

2. The compound of claim 1 , wherein:
R″ is a hydrogen atom;
n′ is 1;
n is 1 or 2;
R independently represents a hydrogen atom, a halogen atom, or a group selected from a (C 1 -C 3 )alkyl group, a —CN group, a hydroxyl group, a —NR 1 R 2 group, a —COOR 1 group, a (C 1 -C 3 )fluoroalkyl group, a —NO 2 group, and a (C 1 -C 4 )alkoxy group; and
R′ is a hydrogen atom, a halogen atom, or a group selected from a (C 1 -C 3 )alkyl group, a —NR 1 R 2 group, and a (C 1 -C 4 )alkoxy group.

3. The compound of claim 1 , wherein:
R″ is a hydrogen atom or a (C 1 -C 4 )alkyl group;
R independently represent a hydrogen atom, a halogen atom, or a group selected from a (C 1 -C 3 )alkyl group, a —CN group, and a (C 1 -C 3 )fluoroalkyl group;
R′ is a hydrogen atom, or a halogen atom;
n′ is 1; and
n is 1;

with the proviso that when n is 1:
R is not a methyl group in ortho or para position with respect to N, and
R is not a bromine atom or a chlorine atom when R′ is a hydrogen atom.

4. The compound of claim 1 , wherein the compound is of formula (Ia′):

where:
R independently represents a hydrogen atom, a (C 1 -C 3 ) alkyl group, a (C 1 -C 3 )fluoroalkyl group, a halogen atom, or a hydroxyl group;
R″ is a hydrogen atom or a (C 1 -C 4 )alkyl group; and
n is 1 or 2.

5. A compound selected from the group consisting of:
(1) (8-Chloro-quinolin-2-yl)-pyridin-2-yl-amine,
(2) 2-(Quinolin-2-ylamino)-isonicotinic acid,
(5) 2-(8-Chloro-quinolin-2-ylamino)-isonicotinic acid,
(6) (8-Chloro-quinolin-2-yl)-(4-methyl-pyridin-2-yl)-amine,
(7) 6-(Quinolin-2-ylamino)-nicotinonitrile,
(18) 8-chloro-N-(6-methylpyridin-2-yl)quinolin-2-amine,
(21) 3-methyl-N-(4-methylpyridin-2-yl)quinolin-2-amine,
(22) 3-methyl-N-(pyridin-2-yl)quinolin-2-amine,
(23) 6-((4-methylquinolin-2-yl)amino)nicotinonitrile,
(24) 6-((3-methylquinolin-2-yl)amino)nicotinonitrile,
(25) 6-chloro-N-(4-methylpyridin-2-yl)quinolin-2-amine,
(26) 6-chloro-N-(6-methylpyridin-2-yl)quinolin-2-amine,
(27) 4-methyl-N-(5-nitropyridin-2-yl)quinolin-2-amine,
(28) N-(3-nitropyridin-2-yl)quinolin-2-amine,
(29) 8-chloro-N-(3-nitropyridin-2-yl)quinolin-2-amine,
(30) 2-((4-methylquinolin-2-yl)amino)nicotinonitrile,
(31) N-(3-methylpyridin-2-yl)quinolin-2-amine,
(32) N-(5-methylpyridin-2-yl)quinolin-2-amine,
(33) 2-(quinolin-2-ylamino)isonicotinonitrile,
(34) N-(5-(trifluoromethyl)pyridin-2-yl)quinolin-2-amine,
(35) 8-chloro-N-(3-methylpyridin-2-yl)quinolin-2-amine,
(36) 8-chloro-N-(5-methylpyridin-2-yl)quinolin-2-amine,
(37) 8-chloro-N-(5-(trifluoromethyl)pyridin-2-yl)quinolin-2-amine,
(38) N-(3-methoxypyridin-2-yl)quinolin-2-amine,
(39) N-(5-nitropyridin-2-yl)quinolin-2-amine,
(40) 6-((8-chloroquinolin-2-yl)amino)nicotinonitrile,
(41) N-(5-fluoropyridin-2-yl)quinolin-2-amine,
(42) N-(6-(trifluoromethyl)pyridin-2-yl)quinolin-2-amine,
(43) 8-chloro-N-(5-fluoropyridin-2-yl)quinolin-2-amine,
(44) 2-((8-chloroquinolin-2-yl)amino)nicotinic acid,
(46) 3-methyl-N-(6-methylpyridin-2-yl)quinolin-2-amine,
(47) 5-cyano-2-(quinolin-2-ylamino)pyridin-1-ium chloride,
(48) 2-((8-chloroquinolin-2-yl)amino)-4-methylpyridin-1-ium chloride,
(49) 8-chloro-N-(4-ethylpyridin-2-yl)quinolin-2-amine,
(50) 8-chloro-N-(6-ethylpyridin-2-yl)quinolin-2-amine,
(51) 8-chloro-N-(4,6-dimethylpyridin-2-yl)quinolin-2-amine,
(52) 6-((8-chloroquinolin-2-yl)amino)-2-methylnicotinonitrile,
(53) 8-chloro-N-(4-chloropyridin-2-yl)quinolin-2-amine,
(54) 8-methyl-N-(4-methylpyridin-2-yl)quinolin-2-amine,
(55) N-(5-bromo-4-methylpyridin-2-yl)-8-chloroquinolin-2-amine,
(56) 8-chloro-N-(3-ethyl-6-methylpyridin-2-yl)quinolin-2-amine,
(57) 8-fluoro-N-(4-methylpyridin-2-yl)quinolin-2-amine,
(58) 8-bromo-N-(4-methylpyridin-2-yl)quinolin-2-amine,
(59) methyl 6-(quinolin-2-ylamino)nicotinate,
(60) methyl 6-[(8-chloroquinolin-2-yl)amino]pyridine-3-carboxylate,
(61) methyl 6-[(3-methylquinolin-2-yl)amino]pyridine-3-carboxylate,
(62) methyl 2-[(8-chloroquinolin-2-yl)amino]pyridine-3-carboxylate,
(63) 8-methoxy-N-(4-methylpyridin-2-yl)quinolin-2-amine,
(64) N-(4-methylpyridin-2-yl)-5-nitroquinolin-2-amine,
(65) 2-N-(4-methylpyridin-2-yl)quinoline-2,8-diamine,
(66) N-(4-methylpyridin-2-yl)-5-aminoquinolin-2-amine,
(67) methyl 6-[(4-methylquinolin-2-yl)amino]pyridine-3-carboxylate,
(68) 8-chloro-N-[4-(trifluoromethyl)pyridin-2-yl]quinolin-2-amine,
(69) 2-[(8-chloroquinolin-2-yl)amino]pyridin-3-ol,
(70) 8-chloro-N-[6-(trifluoromethyl)pyridin-2-yl]quinolin-2-amine,
(71) 6-chloro-N-(5-fluoropyridin-2-yl)quinolin-2-amine,
(72) N-(6-ethylpyridin-2-yl)-3-methylquinolin-2-amine,
(73) N-(5-fluoropyridin-2-yl)-3-methylquinolin-2-amine
(74) 3-methyl-N-[5-(trifluoromethyl)pyridin-2-yl]quinolin-2-amine,
(150) N-(4-methylpyridin-2-yl)-8-nitroquinolin-2-amine,
(151) 6-chloro-N-(6-ethylpyridin-2-yl)quinolin-2-amine,
(152) 6-chloro-N-(5-methylpyridin-2-yl)quinolin-2-amine,
(153) 6-chloro-N-[5-(trifluoromethyl)pyridin-2-yl]quinolin-2-amine,
(154) N2-(8-chloroquinolin-2-yl)-4-methylpyridine-2,3-diamine,

and pharmaceutically acceptable salts thereof, wherein the pharmaceutically acceptable salts are selected from hydrobromide, tartrate, citrate, trifluoroacetate, ascorbate, hydrochloride, tartrate, triflate, maleate, mesylate, formate, acetate, and fumarate.

6. A pharmaceutical composition comprising at least one compound as defined in claim 1 .

7. A pharmaceutical composition comprising at least one compound as defined in claim 2 .

8. A pharmaceutical composition comprising at least one compound as defined in claim 3 .

9. A pharmaceutical composition comprising at least one compound as defined in claim 4 .

10. A pharmaceutical composition comprising at least one compound as defined in claim 5 .

11. The pharmaceutical composition according to claim 6 , further comprising a pharmaceutically acceptable support.

12. The pharmaceutical composition according to claim 7 , further comprising a pharmaceutically acceptable support.

13. The pharmaceutical composition according to claim 8 , further comprising a pharmaceutically acceptable support.

14. The pharmaceutical composition according to claim 9 , further comprising a pharmaceutically acceptable support.

Assignees

• Soc Splicos
• Centre Nat Rech Scient
• Inst Curie
• Univ Montpellier 2
• Abivax
• Univ Montpellier

Inventors

• Tazi Jamal
• Mahuteau Florence
• Najman Romain
• Scherrer Didier
• Campos Noelie
• Garcel Aude

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/4709 Primary

  Non-condensed quinolines and containing further heterocyclic rings · CPC title

• C07D215/42

  attached in position 4 · CPC title

• C07D213/74

  Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals · CPC title

• A61K31/4985

  Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems · CPC title