Substituted morpholine derivatives and their use as therapeutic agents

摘要

PCT No. PCT/GB94/02819 Sec. 371 Date Jun. 13, 1996 Sec. 102(e) Date Jun. 13, 1996 PCT Filed Dec. 23, 1994 PCT Pub. No. WO95/18124 PCT Pub. Date Jul. 6, 1995 <IMAGE> (I) The present invention relates to compounds of formula (I), wherein R1 is hydrogen, halogen, C1-6C alkyl, C1-6 alkoxy, CF3, NO2, CN, SRa, SORa, SO2Ra, CO2Ra, CONRaRb, C2-6 alkenyl, C2-6 alkynyl or C1-4 alkyl substituted by C1-4 alkoxy, where Ra and Rb are hydrogen or C1-4 alkyl; R2 is hydrogen, halogen, C 1-6 alkyl, C1-6 alkoxy substituted by C1-4 alkoxy or CF3; R3 is hydrogen, halogen or CF3; R4 is selected from the definitions of R1; R5 is selected from the definitions of R2; R6 is a 5-membered or 6-membered heterocyclic ring containing 2 or 3 nitrogen atoms optionally substituted by =O, =S or a C1-4 alkyl group, and optionally substituted by an aminoalkyl group; R9a and R9b are hydrogen or C1-4 alkyl, or R9a and R9b are joined to form a C5-7 ring; X is C1-4 alkylene optionally substituted by oxo; and Y is a C1-4 alkyl group optionally substituted by hydroxyl; with the proviso that if Y is C1-4 alkyl, R6 is substituted at least by an aminoalkyl group; and pharmaceutically acceptable salts and prodrugs thereof. The compounds are of particular use in the treatment of pain, inflammation, migraine and emesis.