Fluoromethyl-substituted pyrolocarboxamides as Ca channel blockers CaV2.2

摘要

Compound of general formula (I), ** (See formula) ** characterized in that n represents 0, 1 or 2; R1 represents (C1-6) alkyl, (C2-6) alkenyl, (C2-6) alkynyl, (C3-6) cycloalkyl or 3-7 membered heterocyclyl; R2 represents CH2 F; CHF2 or CF3; R3 represents H, (C1-6) alkyl, (C3-6) cycloalkyl or 3-7 membered heterocyclyl; OH, O-C1-6alkyl, NH2, N (H) C1-6alkyl, N (C1-6alkyl) 2 or SO2-C1-6alkyl; (Het) aryl represents aryl or heteroaryl, each substituted with zero or one or two or three substituents from the group consisting of R6, R7 and R8, where R6, R7 and R8, are independently selected from each other, from the group consisting of F, Cl, Br, I, NO2, CN, (C1-6) alkyl, CF3, CF2H, CFH2, CF2Cl, CFCl2, C ( = O) -H, C ( = O) -C1-6 alkyl, C ( = O) -OH, C ( = O) -O-C1-6 alkyl, C ( = O) -N (H) (OH), C ( = O) -NH2, C ( = O) -N (H) (C1-6) alkyl, C ( = O) -N ((C1-6) alkyl) 2, C ( = N-OH) -H, C ( = N-OH) -C1-6alkyl, C ( = NO-C1-6alkyl) - H, C ( = NO-C1-6alkyl) - C1-6alkyl, OH , OCF3, OCF2H, OCFH2, OCF2Cl, OCFCl2, O (C1-6) alkyl, OC ( = O) -C1-6 alkyl, OC ( = O) -O (C1-6) alkyl, O- (C = O) -N (H) (C1-6) alkyl, OC ( = O) -N ((C1-6) alkyl) 2, OS ( = O) 2-(C1-6) alkyl , OS ( = O) 2- OH, OS ( = O) 2-O-C1-C6-alkyl, OS ( = O) 2-NH2, OS ( = O) 2-N (H) C1-6alkyl, OS ( = O) 2-N (C1-6alkyl) 2, NH2, N (H) C1-6alkyl, N (C1-6alkyl) 2, N (H) -C ( = O) -C1-6 alkyl, N (H) -C ( = O) -O-C1-6 alkyl, N (H) - C ( = O ) -NH2, N (H) -C ( = O) -N (H) (C1-6) alkyl, N (H) -C ( = O) -N (C1-6 alkyl) 2, N (C1-6 alkyl) - C ( = O) - C1-6 alkyl, N (alkyl (C1-6)) - C ( = O) -O-C1-6 alkyl, N (C1-6 alkyl) - C ( = O) -NH2, N (C1-6 alkyl) ) -C ( = O) - N (H) C 1-6 alkyl, N (C 1-6 alkyl) - C ( = O) -N (C 1-6 alkyl) 2, N ( H) -S ( = O) 2OH, N (H) -S ( = O) 2-C1-6alkyl, N (H) -S ( = O) 2-O-C1-alkyl 6), N (H) -S ( = O) 2-NH2, N (H) -S ( = O) 2-N (H) (C1-6) alkyl, N (H) - S ( = O) 2N (C 1-6 alkyl) 2, N (C 1-6 alkyl) - S ( = O) 2-OH, N (C 1-6 alkyl) - S ( = O) 2-C 1-6 alkyl, N (C 1-6 alkyl) - S ( = O) 2-O-C 1-6 alkyl, N (C 1-6 alkyl) - S ( = O) 2-NH2, N ((C1-6) alkyl) - S ( = O) 2-NH2, N ((C1-6) alkyl) - S ( = O) 2- N (H) alkyl ( C1-6), N (C1-6 alkyl) - S ( = O) 2-N (C1-6 alkyl) 2, SH, SCF3, SCF2H, SCFH2, SCF2Cl, SCFCl2, S-alkyl ( C1-6), S ( = O) -C1-6 alkyl, S ( = O) 2-C1-6 alkyl, S ( = O) 2-OH, S ( = O) 2-O-C 1-6 alkyl, S ( = O) 2-NH2, S ( = O) 2-N (H) C 1-6 alkyl, S ( = O) 2-N ( C 1-6 alkyl) 2, C 3-6 cycloalkyl or 3-7 membered heterocyclyl; R4 represents H, (C1-10) alkyl, aryl or aryl connected via a (C1-6) alkylene group; R5 represents H, (C1-10) alkyl, (C3-10) cycloalkyl, heterocyclyl, aryl or 3-10 membered heteroaryl; or 3- to 10-membered C3-10 cycloalkyl, heterocyclyl, aryl or heteroaryl linked in each case via a (C1-6) alkylene group; or R4 and R5, together with the connecting nitrogen atom, form a 3-10 membered heterocyclyl; where (C1-6) alkyl, (C1-10) alkyl, (C2-6) alkenyl, (C2-6) alkynyl and (C1-6) alkylene in each case can be linear or branched and unsubstituted or mono - or poly-substituted; and where (C3-6) cycloalkyl, (C3-10) cycloalkyl, 3-7 membered heterocyclyl, heterocyclyl, aryl and 3-10 membered heteroaryl in each case can be substituted or mono- or poly-substituted; optionally in the form of a single stereoisomer or a mixture of stereoisomers, in the form of a free compound and / or a physiologically acceptable salt and / or a physiologically acceptable solvate thereof.