Derivatives of 1-OXO-1,2-dihydroisoquinoline-5-carboxamides and of 4-OXO-3,4-dihydroquinazoline-8-carboxamides, preparation thereof and application thereof in therapeutics

1. A compound of formula (I):

wherein:

R1 is hydrogen, (C 1 -C 10 )alkyl, (C 3 -C 7 )cycloalkyl, (CH 2 ) n —(C 2 -C 6 )alkenyl, (CH 2 ) n —(C 2 -C 6 )alkynyl, (C 1 -C 6 )alkyl-Z—(C 1 -C 6 )alkyl, COOR, S(O) m R, aryl or aralkyl, wherein the (C 1 -C 10 )alkyl, (C 3 -C 7 )cycloalkyl, (CH 2 ) n —(C 2 -C 6 )alkenyl, (CH 2 ) n —(C 2 -C 6 )alkynyl, (C 1 -C 6 )alkyl-Z—(C 1 -C 6 )alkyl, aryl and aralkyl are optionally substituted with one or more groups chosen from halogen, (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy, NR7R8, nitro, cyano, OR, COOR, CONR7R8, S(O) m NR7R8 and aryl;

R2 is one or more groups chosen from hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, (C 2 -C 6 )alkenyl, C 2 -C 6 alkynyl, (C 1 -C 6 )alkyl-Z—(C 1 -C 6 )alkyl, halo(C 1 -C 1-6 )alkyl, halo(C 1 -C 6 )alkoxy, hydroxy, (C 1 -C 6 )alkoxy, nitro, cyano, amino, NR7R8, COOR, CONR7R8, OCO(C 1 -C 6 )alkyl, S(O) m —NR7R8 and aryl, wherein the aryl is optionally substituted with one or more groups chosen from halogen, (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy, NR7R8, OR, nitro, cyano, COOR, CONR7R8 and S(O) m NR7R8;

R3 is trifluoromethyl;

R4 and R5 are hydrogen, or

R4 and R5 taken together with the carbon atom to which they are attached form a saturated ring containing from 3 to 6 carbon atoms and optionally containing from 0 to 1 heteroatom chosen from O, N and S;

R6 is hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, (C 3 -C 7 )cycloalkyl(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, nitro, amino, NR7R8, COOR, NR7(SO 2 )R8, CONR7R8 or aryl, wherein the aryl is optionally substituted with one or more groups chosen from halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy and cyano;

R, R7 and R8 are, independently of one another, hydrogen, (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, (C 3 -C 7 )cycloalkyl(C 1 -C 6 )alkyl, aryl or aryl(C 1 -C 6 )alkylene, or

R7 and R8 taken together with the nitrogen atom to which they are attached may form a saturated, partially unsaturated or unsaturated ring containing from 5 to 7 carbon atoms and optionally containing, in addition, a heteroatom chosen from O, N and S(O) m ;

X is a nitrogen atom;

Z is O, N and S(O) m ;

m is 0, 1 or 2; and

n is 1, 2, 3, 4, 5 or 6;

or a pharmaceutically acceptable acid addition salt thereof.

2. The compound according to claim 1 , wherein

R1 is (C 1 -C 10 )alkyl, which is optionally substituted with one or more (C 1 -C 6 )alkyl groups;

R2, R4 and R5 are hydrogen; and

R6 is hydrogen or halogen;

or a pharmaceutically acceptable acid addition salt thereof.

3. The compound according to claim 1 , which is selected from:

N-[(1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl]-6-chloro-4-oxo-3-(1-propylbutyl)-3,4-dihydroquinazoline-8-carboxamide and its hydrochloride; and

N-[(1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl]-4-oxo-3-(1-propylbutyl)-3,4-dihydroquinazoline-8-carboxamide and its hydrochloride.

4. A pharmaceutical composition, comprising the compound according to claim 1 , or a pharmaceutically acceptable acid addition salt thereof and at least one pharmaceutically acceptable excipient.

5. A pharmaceutical composition, comprising the compound according to claim 2 , or a pharmaceutically acceptable acid addition salt thereof and at least one pharmaceutically acceptable excipient.

6. A pharmaceutical composition comprising the compound according to claim 3 or a pharmaceutically acceptable salt thereof, in combination with at least one pharmaceutically acceptable excipient.