IP Library › Granted Patent US 9,908,869

Granted Patent B2

US 9,908,869 · App. 14/256,334 · Granted Mar 6, 2018

Compounds useful for treating aids

Inventors: Jamal Tazi (Clapiers, FR); Florence Mahuteau (Saint Remy les Chevreuses, FR); Romain Najman (L'Hay-les-Roses, FR); Didier Scherrer (Castelnau le Lez, FR); Noelie Campos (Le Cres, FR); Aude Garcel (Le Cres, FR)

Assignees: ABIVAX; CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE; INSTITUT CURIE; UNIVERSITE DE MONTPELLIER

C07D403/12 A61K31/4709 A61K31/4985 C07D213/74 C07D215/38 C07D215/42 C07D215/46 C07D241/44 C07D401/12

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Quick Facts

Patent No.: US 9,908,869
App. No.: 14/256,334
Granted: Mar 6, 2018
Kind: B2

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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″.

Claims (198)

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′ 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.

15. The pharmaceutical composition according to claim 10 , further comprising a pharmaceutically acceptable support.

16. A method of inhibiting replication of HIV-1 in a patient infected with HIV-1 comprising administering to a patient in need thereof an effective quantity of at least one compound of formula (Ia) or a pharmaceutically acceptable salt thereof to thereby inhibit replication of HIV-1:

wherein:

R″ is a hydrogen atom or a (C 1 -C 4 )alkyl group;

n′ is 1;

n is 1, 2, or 3;

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″.

17. The method of claim 16 , wherein:

R independently represents a hydrogen atom, a halogen atom, a (C 1 -C 3 )alkyl group, a —CN group, a hydroxyl group, a (C 1 -C 3 )fluoroalkyl group, a —COOH group, or a (C 1 -C 3 )alkoxy group, and

R′ is a hydrogen atom, a halogen atom, or a (C 1 -C 3 )alkyl group.

18. A method of inhibiting replication of HIV-1 in a patient infected with HIV-1 comprising administering to a patient in need thereof a quantity effective to inhibit replication of HIV-1 at least one 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.

19. The method of claim 18 , wherein the compound is selected from the group consisting of the compounds (1), (2), (5)-(7), (18), (21)-(44), (46)-(74), and (150)-(154), and pharmaceutically acceptable hydrobromide, tartrate, citrate, trifluoroacetate, ascorbate, hydrochloride, tartrate, triflate, maleate, mesylate, formate, acetate, and fumarate salts thereof.

20. The method of claim 16 , wherein the compound is administered in a pharmaceutical composition.

21. The method of claim 19 , wherein the compound is administered in a pharmaceutical composition.

22. The method of claim 16 , wherein the individual is a patient having HIV or AIDS.

23. The method of claim 22 , wherein the compound is orally administered to the patient.

24. The method of claim 18 , wherein the individual is a patient having HIV or AIDs.

25. The method of claim 24 , wherein the compound is orally administered to the patient.

Assignments (2)

MERGER AND CHANGE OF NAME Recorded Dec 1, 2015

From: UNIVERSITE DE MONTPELLIER 2; UNIVERSITE MONTPELLIER 2

To: UNIVERSITE DE MONTPELLIER

Reel/Frame 037179/0237 →

MERGER Recorded Jan 20, 2015

From: SPLICOS

To: ABIVAX

Reel/Frame 034759/0705 →

Priority Claims (2)

EP 09162630 · Jun 12, 2009 · regional

EP 09305540 · Jun 12, 2009 · regional

Continuity (4)

Continuation 13377760

Provisional Application 61186552 · Jun 12, 2009

Provisional Application 61186544 · Jun 12, 2009

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