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1. (WO2001032622) POSITIVE MODULATORS OF NICOTINIC RECEPTOR AGONISTS

Pub. No.:    WO/2001/032622    International Application No.:    PCT/SE2000/002147
Publication Date: Fri May 11 01:59:59 CEST 2001 International Filing Date: Thu Nov 02 00:59:59 CET 2000
IPC: A61K 45/06
C07D 209/12
C07D 209/42
Applicants: ASTRAZENECA AB
GURLEY, David
ROSAMOND, James
Inventors: GURLEY, David
ROSAMOND, James
Title: POSITIVE MODULATORS OF NICOTINIC RECEPTOR AGONISTS
Abstract:
A compound of Formula (I), wherein R1 represents hydrogen, C¿1?-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, or (CH2)nAr; W represents C(O), C(O)O, C(O)NR?6¿, or a bond; R2 represents hydrogen, Ar, or (CH¿2?)pCH[(CH2)qR?7](CH¿2)tR8; or together R?2 and R6¿ represent (CH¿2?)jY(CH2)k; R?3 and R5¿ independently represent hydrogen, halogen, or C¿1?-C4 alkyl; X represents oxygen, or NH; R?4¿ represents hydrogen, C¿1?-C4 alkyl(CH2)uAr, R?9¿CO, or R9SO2; R6 represents hydrogen, C¿1?-C4 alkyl, aryl or heteroaryl, or together R?2 and R6¿ represent (CH¿2?)jY(CH2)k; R?7 and R8¿ independently represent hydrogen, halogen, CN, -C CH, N¿3?, CF3, NO2, Ar, OR?10, NR10R11¿, C(O)OR10, OC(O)R10, C(O)NR?10R11, NR10C(O)R11, SO¿2NR?10R11, or NR10SO¿2R11; R9 represents C¿1?-C4 alkyl, or Ar; Ar represents phenyl, naphthyl, or a 5- or 6-membered heterocyclic ring containing 0-3 nitrogens, 0-1 sulfurs and 0-1 oxygens; Ar is optionally substituted with one or more substituents independently selected from: hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, (CH2)naryl, CN, NO2, CF3, OR?12, NR12R13¿ and COOR?12; R10, R11, R12 and R13¿ independently represent hydrogen, C¿1?-C4 alkyl, aryl, or heteroaryl; or together R?10 and R11¿ and/or R?12 and R13¿ independently represent (CH¿2?)jY(CH2)k; Y represents oxygen, sulfur, NR?14¿, or a bond; j is 2-4; k, m, n, p, q, t and u are independently 0-2; R14 represents hydrogen, C¿1?-C4 alkyl, aryl or heteroaryl; or an enantiomer thereof,and pharmaceutically acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy, especially for treatment of conditions associated with reductions in nicotinic transmission. The compounds of the invention enhance the efficacy of agonists at nicotinic receptors.