Patent TW-200524871-A (TW)
Title: Chemical compounds
Inventor: HAMLYN RICHARD JOHN
Filed: 2004-07-07
Abstract: Compounds of the formula (1), and pharmaceutically acceptable salts thereof, are found to be antagonists of SNS sodium channels. They are therefore useful as analgesic and neuroprotective agents, wherein: - X is-N-or -CH-; - n is from 0 to 3; - each R1 is the same or different and is a hydroxy, amino, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, (C1C6 alkyl)amino or di(C1-C6 alkyl)amino group; - p is 0 or 1; - R1/ is cyano, -NR/-CO-(C1-C4 alkyl), -NR/-S(O)2-(C1-C4 alkyl), -CO2H, - S(O)2OH, -CO2-(C1-C4 alkyl), -O-S(O)2-(C1-C4 alkyl) or -N[S(O)2-(C1-C4 alkyl)]2, wherein R/ is hydrogen or a C1-C4 alkyl group; - m is 1, 2 or 3; and - R2 is either (i) -L-A, wherein L is a direct bond or a C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl moiety and A is C6-C10 aryl, C3-C6 carbocyclyl, a 5-to 10- membered heteroaryl group or a 5-to 10- membered heterocyclic group, (j) -L-CR(A)2 or -L-CH=C(A)2 wherein R is hydrogen or C1-C4 alkyl, L is as defined above and each A is the same or different and is as defined above, (k) -L)Het-A), wherein Het is -O-, -S- or -NR)-, A) is -L-A, -L-CR(A)2 or -L-CH-C(A)2, R) is H or -L-A, L) is a C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl moiety, L is as defined above, R is as defined above and each A is the same or different and is as defined above, (1) -L-CO-NR3R4 or -L-CS-NR3R4, wherein L is as defined above and either (i) R3 and R4, together with the N atom to which they are attached, form a 5- to 10- membered heteroaryl or heterocyclyl group or (ii) R3 represents -L-H or A) wherein L and A) are as defined above, and R4 represents -L)-H, -L)-CO-A), -L)-S(O)-A), -L)-S(O)2-A), -L)-Het-A), -NR-CO-N(A)2, -N(A)2, -A-Het-A, -A), -L-CR(LA)2 or -L-CH=C(LA)2 wherein each L is the same or different, each A is the same or different, and L), L, R, A and A) are as defined above, (m) -CO-L-NR3R4 or -CS-L-NR3R4 wherein L, R3 and R4 are as defined above, (n) -CO-A) or -CS-A) wherein A) is as defined above, (o) -L/-O-N-C(A)2 or -CO-L)-O-N=C(A)2 wherein L) is as defined above and each A is the same or different and is as defined above, or (p) -L)-NR-CO-NR3R4 or -L)-NR-CS-NR3R4, wherein L), R, R3 and R4 are as defined above, wherein - said aryl, carbocyclyl, heteroaryl and heterocyclyl groups are optionally fused to one or two cyclic moieties selected from phenyl rings and 5-to 6- membered heterocyclyl and heteroaryl groups, and - said aryl, heteroaryl, carbocyclyl and heterocyclyl groups are unsubstituted or are substituted by 1, 2 or 3 substituents which are the same or different and are selected from C1-C4 alkyl, C1-C4 haloalkyl, halogen, hydroxy, amino, (C1-C4 alkyl)amino, di(C1-C4 alkyl)amino, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 haloalkylthio, -NH-CO-(C1-C4 alkyl), -CO-(C1-C4 alkyl), -CO2-(C1-C4 alkyl), 5- or 6- membered heteroaryl, phenyl and -CHPh2 substituents, the phenyl and heteroaryl moieties in said substituents being unsubstituted or substituted by 1 or 2 further substituents selected from halogen atoms, C1-C2 alkyl groups, C1-C2 alkoxy groups and -NH-CO-(C1-C2 alkyl) groups, provided that (a) when R2 is -L-A, A is other than a benzimidazole group, and (b) when R2 is -CO-A or -CS-A/, A is other than a pyrazolopyrimidine or pyrazole group.