AZACYCLIC COMPOUNDS AS INHIBITORS OF SENSORY NEURONE SPECIFIC SODIUM CHANNELS

摘要

Compounds of the formula (I), and pharmaceutically acceptable salts thereof, are found to be antagonists of SNS sodium channels. They are therefore useful as analgesic and neuroprotective agents; wherein (1) represents (A), (B) or (C); R¹ represents: (a) -L-A or L′-A′ wherein L represents a bond or a C₁-C₆ alkyl, C₂-C₆ alkenyl or C₂-C₆ alkynyl moiety, A represents a phenyl, 5- to 10-membered heteroaryl, C₃-C₆ carbocyclyl or 5- to 10 membered heterocyclyl group, L′ represents a C₁-C₆ alkyl, C₂-C₆ alkenyl or C₂-C₆ alkynyl moiety, and A′ represents -Het-A or —X-A wherein Het represents —O—, —S— or NR′, and X represents —CO—, —SO—, SO₂—, —CO—O—, CO—S, CONR′, —O—CO—, —S—CO— or NR′—CO—, wherein R′ represents hydrogen or C₁-C₆ alkyl; (b) -L-A-A′ or -L-A-L-A wherein A′ is as defined above, each A is the same or different and is as defined above and each L is the same or different and is as defined above; (c) -A-Z-A wherein Z is -Het-L′, —X-L′, -L′-Het- or L′-X, wherein Het, L′ and X are as defined above and each A is the same or different and is as defined above; (d) -A-Het-Y or -A-X—Y wherein is [L′-Het]_n-L′, [L′-Het]_n-L′, -[L′-Het]_n-A, -L′-B-L′, -L′-B-A or -A-L-A wherein n is from 1 to 4 and B is —X—, —NR′—CO—NR′, —O—CO—NR′— or —NR′—CO—O, and wherein X and L are as defined above, each A is the same or different and is as defined above, each L′ is the same or different and is as defined above, each R′ is the same or different and is as defined above and each Het is the same or different and is as defined above; or (e) -L-CR(A)(A′) or L-CR(A)(L-A) wherein R is hydrogen or C₁-C₄ alkyl, A′ is as defined above, each L is the same or different and is as defined above and each A is the same or different and is as defined above; R² represents -L-A-, L′-A′, -L-A-A′ or L-A-L-A wherein L′ and A′ are as defined above, each L is the same or different and is as defined above and each A is the same or different and is as defined above J represents —NR³—, —O— or a direct bond wherein R³ represent s hydrogen C₁-C₆ alkyl, C₂-C₆ alkenyl or C₂-C₆ alkynyl; p is an integer from 1 to 3; q is 1 or 2; and one of E and E′ is —CH₂— and the other is a direct bond.;