Compounds useful for treating AIDS

1. A method of inhibiting replication of HIV-1 in a patient infected with HIV-1, comprising:

administrating to the patient an effective quantity of a compound of formula (I) or a pharmaceutically acceptable salt thereof to inhibit replication of HIV-1:

wherein:

X is CR 0 or N, i.e. forms together with the ring to which it belongs respectively a benzene or a pyridine group,

R 0 , R 1 , R 2 , R 3 , R 4 , R 7 , and R 8 independently represent:

a hydrogen atom,

a halogen atom, or

a group selected from:

a (C 1 -C 5 )alkyl group,

a (C 3 -C 6 )cycloalkyl group,

a (C 1 -C 5 )fluoroalkyl group,

a (C 1 -C 5 )alkoxy group,

a (C 1 -C 5 )fluoroalkoxy group,

a —CN group,

a —COOR a group,

a —NO 2 group,

a —NR a R b group,

a —NR a —SO 2 —NR a R b group,

a —NR a —SO 2 —R a group,

a —NR a —C(═O)—R a group,

a —NR a —C(═O)—NR a R b group,

a —SO 2 —NR a R b group,

a —SO 3 H group,

a —OH group,

a —O—SO 2 —OR c group,

a —O—P(═O)—(OR c )(OR d ) group,

a —O—CH 2 —COOR c group,

where:

A is a covalent bond, an oxygen atom, or NH,

B is a covalent bond or NH,

n is 1, 2, 3, 4 or 5,

m is 1, 2, or 3,

R, R′, R a , and R b independently represent a hydrogen atom, a (C 1 -C 5 )alkyl group, or a (C 3 -C 6 )cycloalkyl group,

R and R′ can further form together with the nitrogen atom to which they are attached a saturated 5- or 6-membered heterocycle optionally containing a further heteroatom selected from N, O, and S, said heterocycle being optionally substituted by one or more R,

R c and R d independently represent a hydrogen atom, Li + , Na + , K + , N + (R a ) 4 or a benzyl group,

R 5 represents a hydrogen atom, a (C 1 -C 5 )alkyl group, or a (C 3 -C 6 )cycloalkyl group,

R 10 is a hydrogen atom or a chlorine atom, and

R 11 is a hydrogen atom or a (C 1 -C 4 )alkyl group;

provided that at least three of R 5 , R 7 , R 8 , and R 10 are different from a hydrogen atom, or alternatively

provided that one of R 7 and R 8 is a hydrogen atom and the other of R 7 and R 8 is a group selected from:

a —NR a —SO 2 —NR a R b group,

a —NR a —SO 2 —R a group,

a —NR a —C(═O)—R a group, and a —NR a —C(═O)—NR a R b group, or alternatively provided that one of R 0 , R 1 , R 2 , R 3 and R 4 is a group selected from:

a —NR a —SO 2 —NR a R b group,

a —NR a —SO 2 —R a group,

a —NR a —C(═O)—R a group, and

a —NR a —C(═O)—NR a R b group.

2. A compound of formula (I) or a pharmaceutically acceptable salt thereof:

wherein:

X is CR 0 or N, i.e. forms together with the ring to which it belongs respectively a benzene or a pyridine group,

R 1 , R 2 , R 3 , R 7 and R 8 independently represent:

a hydrogen atom,

a halogen atom, or

a group selected from:

a (C 1 -C 5 )alkyl group,

a (C 3 -C 6 )cycloalkyl group,

a (C 1 -C 5 )fluoroalkyl group,

a (C 1 -C 5 )alkoxy group,

a (C 1 -C 5 )fluoroalkoxy group,

a —CN group,

a —COOR a group,

a —NO 2 group,

a —NR a R b group,

a —NR a —SO 2 —NR a R b group,

a —NR a —SO 2 —R a group,

a —NR a —C(═O)—R a group,

a —NR a —C(═O)—NR a R b group,

a —SO 2 —NR a R b group,

a —SO 3 H group,

a —OH group,

a —O—SO 2 —OR c group,

a —O—P(═O)—(OR c )(OR d ) group,

a —O—CH 2 —COOR c group,

where:

A is a covalent bond, an oxygen atom, or NH,

B is a covalent bond or NH,

n is 1, 2, 3, 4, or 5,

m is 1, 2, or 3,

R, R′, R a , and R b independently represent a hydrogen atom, a (C 1 -C 5 )alkyl group, or a (C 3 -C 6 )cycloalkyl group,

R and R′ can further form together with the nitrogen atom to which they are attached a saturated 5- or 6-membered heterocycle optionally containing a further heteroatom selected from N, O, and S, said heterocycle being optionally substituted by one or more R,

R c and R d independently represent a hydrogen atom, Li + , Na + , K + , N + (R a ) 4 or a benzyl group,

R 0 represents a hydrogen atom or a (C 1 -C 5 )alkyl group,

R 4 represents a hydrogen atom or a (C 1 -C 5 )alkyl group when X is CR 0 ,

R 4 is has the same definition as R 1 , R 2 , R 3 , R 7 , and R 8 above when X is N,

R 5 represents a hydrogen atom, a (C 1 -C 5 )alkyl group, or a (C 3 -C 6 )cycloalkyl group,

R 10 is a hydrogen atom or a chlorine atom, and

R 11 is a hydrogen atom or a (C 1 -C 4 )alkyl group;

provided that at least three of R 5 , R 7 , R 8 , and R 10 are different from a hydrogen atom, or alternatively

provided that one of R 7 and R 8 is a hydrogen atom and the other of R 7 and R 8 is a group selected from:

a —NR a —SO 2 —NR a R b group,

a —NR a —SO 2 —R a group,

a —NR a —C(═O)—R a group, and

a —NR a —C(═O)—NR a R b group, or alternatively

provided that one of R 1 , R 2 , R 3 , and R 4 is a group selected from:

a —NR a —SO 2 —NR a R b group,

a —NR a —SO 2 —R a group,

a —NR a —C(═O)—R a group, and

a —NR a —C(═O)—NR a R b group;

wherein:

when R 2 is —OH, then neither R 1 nor R 3 is a

radical,

when R 8 is a methoxy group then neither R 1 nor R 3 is a

radical,

when R 8 is a —NH—C(═O)—CH 3 group then R 2 is not a —N(CH 3 ) 2 group, and

the following compounds are excluded from the scope of compounds of formula

3. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 2 , wherein:

when X is N, R 4 is a hydrogen atom, a fluorine atom, a NO 2 group, a NH 2 group, a methyl group, a methoxy group, a trifluoromethoxy group,

a —N—SO 2 —N(CH 3 ) 2 group, a —N—SO 2 —CH 3 group, a —N—C(═O)—CH 3 group, or

a —N—C(═O)—NR a R b group,

R 1 and R 3 independently represent a hydrogen atom, a methyl group, a trifluoromethyl group, a chlorine atom, a methoxy group, a trifluoromethoxy group, or a group selected from:

X 1 is O, N(CH 3 ), or CH 2 ,

m is 1 or 2,

R 2 is a hydrogen atom, a fluorine atom, a methyl group, a trifluoromethyl group, a NH 2 group, a methoxy group, a trifluoromethoxy group, a —O—CH 2 —CH 2 —OH group,

a —N—SO 2 —N(CH 3 ) 2 group, a —N—SO 2 —CH 3 group, a —N—C(═O)—CH 3 group, or a —N—C(═O)—NR a R b group,

R 5 represents a hydrogen atom or a methyl group,

R 7 is a hydrogen atom, a NH 2 group, or when R 8 is a hydrogen atom, R 7 can further be a group selected from:

a —N—SO 2 —N(CH 3 ) 2 group, a —N—SO 2 —CH 3 group, a —N—C(═O)—CH 3 group, and

a —N—C(═O)—N(R a )(R b ) group,

n is 1, 2 or 3,

R 8 is a hydrogen atom, a NH 2 group, or when R 7 is a hydrogen atom, R 8 can further be a group selected from:

R 10 is a hydrogen atom or a chlorine atom, and

R 11 is a hydrogen atom or a (C 1 -C 4 )alkyl group,

provided that at least three of R 5 , R 7 , R 8 and R 10 are different from a hydrogen atom, or alternatively

provided that one of R 7 and R 8 is a hydrogen atom and the other of R 7 and R 8 is a group selected from:

R 7 being further able to be a —N—SO 2 —N(CH 3 ) 2 group, a —N—SO 2 —CH 3 group, a —N—C(═O)—CH 3 group, or a —N—C(═O)—NR a R b group when R 8 is a hydrogen atom, or alternatively

provided that R 1 or R 3 is a group selected from:

or alternatively

provided that R 2 , or R 4 when X is N, is a group selected from a —N—SO 2 —N(CH 3 ) 2 group, a —N—SO 2 —CH 3 group, a —N—C(═O)—CH 3 group, and a —N—C(═O)—NR a R b group, and

provided that the following compound is excluded:

4. The compound of formula (I) according to claim 2 , wherein the compound is a compound of formula (A1) or a pharmaceutically acceptable salt thereof:

wherein:

R 1 and R 3 independently represents a hydrogen atom, a methyl group, or a trifluoromethyl group,

R 2 is a hydrogen atom, a fluorine atom, a methyl group, a trifluoromethyl group, a NH 2 group, a N—SO 2 —N(CH 3 ) 2 group, a —N—SO 2 —CH 3 group, a —N—C(═O)—CH 3 group, or a —N—C(═O)—NR a R b group,

R 4 is a hydrogen atom, a NO 2 group, a NH 2 group, a fluorine atom, a methyl group, a —N—SO 2 —N(CH 3 ) 2 group, a —N—SO 2 —CH 3 group, a —N—C(═O)—CH 3 group or

a —N—C(═O)—NR a R b group,

R 5 is a hydrogen atom or a methyl group,

R 7 is a hydrogen atom, a NH 2 group, or when R 8 is a hydrogen atom, R 7 is a group selected from:

a —N—SO 2 —N(CH 3 ) 2 group,

a —N—SO 2 —CH 3 group,

a —N—C(═O)—CH 3 group, and

a —N—C(═O)—NR a R b group,

n is 1, 2, or 3,

m is 1 or 2,

R 8 is a hydrogen atom, a NH 2 group, or when R 7 is a hydrogen atom, R 8 can further be a group selected from:

R 10 is a hydrogen atom or a chlorine atom,

provided that at least three of R 5 , R 7 , R 8 , and R 10 are different from a hydrogen atom, or alternatively

provided that one of R7 and R8 is a hydrogen atom and the other of R 7 and R 8 is a group selected from:

R 7 being further able to be a —N—SO 2 —N(CH 3 ) 2 group, a —N—SO 2 —CH 3 group, a —N—C(═O)—CH 3 group, or a —N—C(═O)—NR a R b group when R 8 is a hydrogen atom, or alternatively

provided that R 2 or R 4 is a group selected from a —N—SO 2 —N(CH 3 ) 2 group, a —N—SO 2 —CH 3 group, a —N—C(═O)—CH 3 group, and a —N—C(═O)—NR a R b group.

5. The compound of formula (I) according to claim 2 , wherein the compound is a compound of formula (B1) or a pharmaceutically acceptable salt thereof:

wherein:

R 0 and R 4 are independently a hydrogen atom, or a methyl group,

R 1 and R 3 independently represent a hydrogen atom, a chlorine atom, a methoxy group, a trifluoromethoxy group, or a group selected from:

X 1 is O, N(CH 3 ), or CH 2 ,

m is 1 or 2,

R 2 is a hydrogen atom, a methoxy group, a trifluoromethoxy group, or a —O—CH 2 —CH 2 —OH group,

R 5 is a hydrogen atom or a methyl group,

R 7 is a hydrogen atom, a NH 2 group, or when R 8 is a hydrogen atom, R 7 is a group selected from:

a —N—SO 2 —N(CH 3 ) 2 group,

a —N—SO 2 —CH 3 group,

a —N—C(═O)—CH 3 group, and

a —N—C(═O)—NR a R b group,

n is 1, 2, or 3,

R 8 is a hydrogen atom, a NH 2 group, or when R 7 is a hydrogen atom, R 8 can further be a group selected from:

R 10 is a hydrogen atom or a chlorine atom,

provided that at least three of R 5 , R 7 , R 8 and R 10 are different from a hydrogen atom, or alternatively

provided that one of R 7 and R 8 is a hydrogen atom and the other of R 7 and R 8 is a group selected from:

R 7 being further able to be a —N—SO 2 —N(CH 3 ) 2 group, a —N—SO 2 —CH 3 group, a —N—C(═O)—CH 3 group, or a —N—C(═O)—NR a R b group when R 8 is a hydrogen atom, or alternatively

provided that R 1 or R 3 is a group selected from:

or alternatively

provided that R 2 is a group selected from a —N—SO 2 —N(CH 3 ) 2 group, a —N—SO 2 —CH 3 group, a —N—C(═O)—CH 3 group, and a —N—C(═O)—NR a R b group, and

provided that the following compound is excluded:

6. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 2 , wherein:

X is N,

R 1 , R 2 , R 8 , and R 11 are each a hydrogen atom,

R 3 is a methyl group or a trifluoromethyl group,

R 4 is a hydrogen atom or a NH 2 group,

R 5 is a hydrogen atom or a methyl group,

R 7 is a hydrogen atom, a NH 2 group, or when R 8 is a hydrogen atom, R 7 can further be a group selected from:

and a —N—SO 2 —N(CH 3 ) 2 group,

n′ is 0, 1, or 2 and

R 10 is a hydrogen atom or a chlorine atom,

provided that at least three of R 5 , R 7 , R 8 , and R 10 are different from a hydrogen atom, or alternatively

provided that R 7 is a group selected from:

and a —N—SO 2 —N(CH 3 ) 2 group.

7. The compound of formula (I) according to claim 2 , wherein the compound is a compound of formula (A1′) or a pharmaceutically acceptable salt thereof:

wherein:

R 3 is a hydrogen atom, a methyl group, or a trifluoromethyl group,

R 4 is a hydrogen atom, a NO 2 group, a NH 2 group, a fluorine atom, a methyl group, a —N—SO 2 —N(CH 3 ) 2 group, —N—SO 2 —CH 3 group, a —N—C(═O)—CH 3 group, or a —N—C(═O)—NR a R b group,

R 5 is a hydrogen atom or a methyl group,

R 7 is a hydrogen atom, a NH 2 group, or a group selected from:

a —N—SO 2 —N(CH 3 ) 2 group,

a —N—SO 2 —CH 3 group,

a —N—C(═O)—CH 3 group,

a —N—C(═O)—NR a R b group,

n is 1, 2 or 3,

n′ is 0, 1 or 2,

m is 1 or 2,

provided that R 5 and R 7 are not hydrogen atom, or alternatively

provided that R 5 is a hydrogen atom and R 7 is selected from

a —N—SO 2 —N(CH 3 ) 2 group,

a —N—SO 2 —CH 3 group,

a —N—C(═O)—CH 3 group, and

a —N—C(═O)—NR a R b group, or alternatively

provided that R 7 is a hydrogen atom and R 4 is selected from a —N—SO 2 —N(CH 3 ) 2 group, —N—SO 2 —CH 3 group, a —N—C(═O)—CH 3 group, and a —N—C(═O)—NR a R b group.

8. The compound of formula (I) according to claim 2 or a pharmaceutically acceptable salt thereof, wherein:

X is CR 0 ,

R 0 , R 1 , R 4 , R 8 and R 11 are independently a hydrogen atom,

R 2 is a methoxy group, a trifluoromethoxy group, or a —O—CH 2 —CH 2 —OH group,

R 3 is a hydrogen atom, a chlorine atom, or a group selected from:

m is 1 or 2,

R 5 is a hydrogen atom or a methyl group,

R 7 is a hydrogen atom, a NH 2 group, or when R 8 is a hydrogen atom, R 7 can further be a group selected from:

and a —NH—SO 2 —N(CH 3 ) 2 group,

n′ is 0, 1, or 2, and

R 10 is a hydrogen atom or a chlorine atom,

provided that at least three of R 5 , R 7 , R 8 , and R 10 are different from a hydrogen atom, or alternatively

provided that R 7 is a group selected from:

and a —N—SO 2 —N(CH 3 ) 2 group, or alternatively

provided that R 3 is a group selected from:

9. The compound of formula (I) according to claim 2 , wherein the compound is a compound of formula (B1′) or a pharmaceutically acceptable salt thereof:

wherein:

R 2 is a hydrogen atom, a methoxy group, a trifluoromethoxy group, or a —O—CH 2 —CH 2 —OH group,

R 3 is a hydrogen atom, a chlorine atom, a methoxy group, a trifluoromethoxy group, a —O—CH 2 —CH 2 —O—CH 2 —CH 2 —O—CH 3 group, or a group selected from:

X 1 is O, N(CH 3 ) or CH 2 ,

m is 1 or 2,

R 5 is a hydrogen atom or a methyl group,

R 7 is a hydrogen atom, a NH 2 group, or when R 8 is a hydrogen atom, R 7 is a group selected from:

a —N—SO 2 —N(CH 3 ) 2 group,

a —N—SO 2 —CH 3 group,

a —N—C(═O)—CH 3 group,

a —N—C(═O)—NR a R b group,

a —NH—SO 2 —N(CH 3 ) 2 group,

n′ is 0, 1, or 2,

n is 1, 2 or 3,

provided that R 5 and R 7 are not a hydrogen atom, or alternatively

provided that R 5 is a hydrogen atom and R 7 is a group selected from:

a —N—SO 2 —N(CH 3 ) 2 group,

a —N—SO 2 —CH 3 group,

a —N—C(═O)—CH 3 group, and

a —N—C(═O)—NR a R b group, or alternatively

provided that R 7 is a hydrogen atom and R 3 is a group selected from:

10. A compound selected from:

(1) 8-chloro-5-(2-morpholinoethoxy)-N-(4-(trifluoromethyl)pyridin-2-yl)quinolin-2-amine,

(2) N2-(8-chloro-5-(2-morpholinoethoxyl)quinolin-2-yl)-4-methylpyridine-2,3-diamine,

(3) 8-chloro-5-(2-(piperidin-1-yl)ethoxy)-N-(4-(trifluoromethyl)pyridin-2-yl)quinolin-2-amine,

(4) 8-chloro-3-methyl-5-(2-(piperidin-1-yl)ethoxy)-N-(4-(trifluoromethyl)pyridin-2-yl)quinolin-2-amine,

(5) N2-(8-chloro-3-methyl-5-(2-(piperidin-1-yl)ethoxy)quinolin-2-yl)-4-methylpyridine-2,3-diamine,

(6) N,N-dimethyl-N′-[2-[(4-trifluoromethylpyridin-2-yl)amino]-8-chloro-5-quinolinyl]sulfamide,

(7) N,N-dimethyl-N′-[2-[(4-trifluoromethylpyridin-2-yl)amino]-3-methyl-5-quinolinyl]sulfamide,

(8) 8-chloro-3-methyl-N2-(4-(trifluoromethyl)pyridin-2-yl)quinoline-2,5-diamine,

(9) N,N-dimethyl-N′-[2-[(4-trifluoromethyl-pyridin-2-yl)amino]-8-chloro-3-methyl-5-quinolinyl]sulfamide,

(10) N′-[2-[(3-amino-4-methylpyridin-2-yl)amino]-8-chloro-5-quinolinyl]N,N-dimethylsulfamide,

(11) N′-[2-[(3-amino-4-methylpyridin-2-yl)amino]-8-chloro-3-methyl-5-quinolinyl]-N,N-dimethylsulfamide,

(12) N2-(3-amino-4-methylpyridin-2-yl)-8-chloro-3-methylquinoline-2,5-diamine,

(13) N′-[2-[(-3-amino-4-methylpyridin-2-yl)amino]-3-methyl-5-quinolinyl]-N,N-dimethylsulfamide,

(14) 8-chloro-5-(2-(piperidin-1-yl)ethoxy)-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine,

(15) 8-chloro-3-methyl-5-(2-(piperidin-1-yl)ethoxy)-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine,

(16) 8-chloro-N-(3-chloro-4-(trifluoromethoxy)phenyl)-5-(2-(piperidin-1-yl)ethoxy)quinolin-2-amine,

(17) 8-chloro-N-(3-chloro-4-methoxyphenyl)-5-(2-morpholinoethoxyl)quinolin-2-amine,

(18) 8-chloro-N2-(3-chloro-4-(trifluoromethoxy)phenyl)-3-methylquinoline-2,5-diamine,

(19) N′-[2-[(3-chloro-4-(trifluoromethoxy)phenyl)amino]-3-methyl-5-quinolinyl]-N,N-dimethylsulfamide,

(20) N′-[2-[(3-chloro-4-(trifluoromethoxy)phenyl)amino]-8-chloro-5-quinolinyl]-N,N-dimethylsulfamide,

(21) N′-[2-[(3-chloro-4-(trifluoromethoxy)phenyl)amino]-8-chloro-3-methyl-5-quinolinyl]-N,N-dimethylsulfamide,

(22) 2-(4-((8-chloroquinolin-2-yl)amino)phenoxy)ethanol,

(23) 8-chloro-N-(4-methoxy-3-(2-morpholinoethoxyl)phenyl)quinolin-2-amine,

(24) 8-chloro-N-(4-methoxy-3-(2-(2-methoxyethoxyl)ethoxy)phenyl)quinolin-2-amine,

(25) 8-chloro-N-(4-methoxy-3-(2-(piperidin-1-yl)ethoxy)phenyl)quinolin-2-amine,

(26)N-[3-methyl-2-[(4-trifluoromethylpyridin-2-yl)amino]-5-quinolinyl]-methanesulfonamide,

(27)N-[2-[(3-chloro-4-(trifluoromethoxy)phenyl)amino]-3-methyl-5-quinolinyl]-methanesulfonamide; and

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

11. A pharmaceutical composition comprising at least one compound of formula (I) or a pharmaceutically acceptable salt thereof as defined in claim 2 .

12. A medicament, comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 2 .

13. A method of treating a subject with a disease resulting from at least one splicing anomaly, comprising administering to the subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 2 .

14. A method of inhibiting replication of HIV-1 in a patient infected with HIV-1, comprising administrating to the patient an effective quantity of a compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 2 to inhibit replication of HIV-1.