Aromatic acetylcholinesterase inhibitors

C - Chemistry – Metallurgy – 07 – C

Patent

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Details

C07C 49/76 (2006.01) A61K 31/045 (2006.01) A61K 31/12 (2006.01) A61K 31/135 (2006.01) A61K 31/185 (2006.01) A61K 31/22 (2006.01) A61K 31/275 (2006.01) C07C 17/35 (2006.01) C07C 17/361 (2006.01) C07C 33/46 (2006.01) C07C 45/45 (2006.01) C07C 45/67 (2006.01) C07C 49/80 (2006.01) C07C 49/82 (2006.01) C07C 49/84 (2006.01) C07C 69/63 (2006.01) C07C 225/22 (2006.01)

Patent

CA 2164303

Compounds of general formula (1), stereoisomers and pharmaceutically acceptable salts thereof, wherein each of Z and Z' are independently H or F; Q is (a), CH(OH), (b); X is H, Br, CL F or CF3; Y is H, Br, Cl, F, OH, OR5, OC(O)R4, N3, CN, NO2, SO3H, CO2R4, NH2. NHR9, NR9R9, C(R6)(R7)(V'R8) or C(O)R7, provided that when both Z and Z' are F, then Y is H or F; V and V' are each independently CH2 or O; R1 is H or CH3; R2, R9 and R'9 are each independently (C1-6)alkyl, or R2 and V-R3 taken together with the carbon atom to which they are attached form a 3-6 membered ring; R3, R6, R7 and R8 are each independently H, (C1-6)alkyl, or (C3-6)cycloalkyl: R4 is H,(C1-10)alkyl (C0-4) aryl or (C3-8)cycloalkyl; and R5 is (C1-10)alkyl benzyl, phenethyl or (C3-6)cycloalkyl, possess anticholinesterase activity and may be used in the treatment of Degenerativa Dementias.

Cette invention concerne des composés de formule (I), des stéréo-isomères et des sels pharmaceutiquement acceptables de ces derniers, qui possèdent une activité anticholinestérasique et peuvent être utilisés dans le traitement des démences dégénératives. Dans cette formule Z et Z' représentent chacun indépendamment H ou F; Q représente (a), CH(OH), (b); X représente H, Br, Cl, F ou CF3; Y représente H, Br, Cl, F, OH, OR5, OC(O)R4, N3, CN, NO2, SO3H, CO2R4, NH2, NHR9, NR9R'9, C(R6)(R7)(V'R8) ou C(O)R7 à condition que lorsque Z et Z' représentent tous les deux F, Y représente H ou F; V et V' représentent chacun indépendamment CH2 ou O; R1 représente H ou CH3; R2, R9, R'9 représentent chacun indépendamment alkyle (C1-6), ou R2 et V-R3 forment ensemble avec l'atome de carbone auquel ils sont liés un cycle à 3-6 éléments; R3, R6, R7 et R8 représentent chacun indépendamment H, alkyle (C1-6) ou cycloalkyle (C3-6); R4 représente H, alkyle (C1-10), aryle alkylène (C0-4) ou cycloalkyle (C3-8); et R5 représente alkyle (C1-10), benzyle, phénétyle ou cycloalkyle (C3-6).

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