| abstract |
Adamantane derivative which is a compound that responds to formula (1), where: m represents 1, 2 or 3, each R1 independently represents a hydrogen or halogen atom; Ar represents a remainder selected from the group of formulas (2); one of R2 and R3 represents halogen, nitro, amino, hydroxyl, or a group selected from (i) C1-6 alkyl optionally substituted by at least one halogen atom, (ii) C3-8 cycloalkyl, (iii) C1-6 alkoxy optionally substituted by at least one halogen atom, and (iv) C3-8 cycloalkyloxy, and the other of R2 and R3 represents a hydrogen or halogen atom; R4 represents a group of formula (3); X represents an oxygen or sulfur atom or a group> N-R8; N is 0 or 1, R5 represents a C1-5 alkyl group that may be optionally substituted by at least one substituent selected from hydroxyl, halogen and C1-6 alkoxy ;; R6 and R7 each independently represents a hydrogen atom, C1-6 alkyl (optionally substituted by at least one substituent selected from hydroxyl, halogen, C1-6 alkoxy, and (di) -C1-4alkylamino (itself optionally substituted by at least one hydroxyl group), or C3-8 cycloalkyl (optionally substituted by at least one substituent selected from hydroxyl, halogen and C1-6 alkoxy) and R8 represents a hydrogen atom or a C1-5 alkyl group that can be optionally substituted by at least one substituent selected from hydroxyl, halogen and C1-6 alkoxy, with the following caveats: a) when n is 0, then A is NHC (O), and (b) when n is 1, X represents oxygen and A is C (O) NH, then R6 and R7 do not both simultaneously represent a hydrogen atom or do not both simultaneously represent an unsubstituted C1-6 alkyl, or when one of R6 and R7 represents a hydrogen atom, then the other of R6 and R7 does not represent a C1-6 alkyl or unsubstituted, and c) when n is 1, X is oxygen, sulfur or> NH and A is NHC (O), then R6 and R7 do not both simultaneously represent a hydrogen atom or both do not simultaneously represent an unsubstituted C1-6 alkyl, or when one of R6 and R7 represents a hydrogen atom, then the other of R6 and R7 does not represent an unsubstituted C1-6 alkyl or -CH2-CH2OH-, or a salt acceptable for pharmaceutical or solvate use thereof. A process for its preparation and intermediaries that are used in said preparation are also described; pharmaceutical compositions containing them; a process to prepare the pharmaceutical compositions; and its use in the preparation of compounds useful as antagonists of the P2X7 receptor for use in the treatment of inflammatory, immune or cardiovascular diseases. |