EP0790248A1 — 3-Aza-piperidone- (tetrahydropyrimidin-2-one) and 3-oxa-piperidone (1,3 oxazin-2-one) derivatives, their preparation and their use as tachykinin/neurokinin antagonists

USPTO Abstract

Compounds of the formula: wherein:    X is O, NH or NR 1 ; R 1 is C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkyl(C 1 -C 4 )alkyl, aryl or aryl (C 1 -C 4 )alkyl; wherein the C 1 -C 6 alkyl group is optionally substituted by fluorine and the C 3 -C 7 cycloalkyl or C 3 -C 7 cycloalkyl(C 1 -C 4 )alkyl group is optionally substituted in the cycloalkyl ring by up to two substituents each independently selected from halo, C 1 -C 4 alkoxy or halo(C 1 -C 4 )alkoxy; R 2 is phenyl optionally substituted with one or two halo substituents, indolyl or thienyl; R 3 is NH 2 , -NR 4 SO 2 (C 1 -C 6 alkyl), -NR 4 SO 2 aryl, -NR 4 CO(C 1 -C 6 alkyl), -NR 4 CO aryl or a 5 to 7-membered N-linked cyclic group incorporating W in the ring wherein W is O, NR 5 , CH(OH), CHCO 2 H, CHN(R 4 ) 2 , CHF, CF 2 , C = O or CH 2 ; R 4 is H or C 1 -C 6 alkyl; R 5 is H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkyl(C 1 -C 6 )alkyl, C 2 -C 6 alkanoyl, C 4 -C 8 cycloalkanoyl, C 3 -C 7 cycloalkyl(C 2 -C 6 )alkanoyl, aryl CO-, C 1 -C 6 alkyl SO 2 -, C 3 -C 7 cycloalkyl SO 2 -, C 3 -C 7 cycloalkyl(C 1 -C 6 )alkyl SO 2 -, aryl-SO 2 - or (R 6 ) 2 NSO 2 -, wherein each R 6 is independently H or C 1 -C 4 alkyl or the two groups may be joined to form with the nitrogen atom to which they are attached, a pyrrolidinyl, piperidino, morphlino or piperazinyl group; m is O, 1 or 2 with the proviso that m is not O when W is NR 5 , C=O, or O; and n is an integer of from 1 to 4; are neurokinin receptor antagonists of utility in the treatment of a variety of medical conditions including urinary incontinence, asthma and related conditions.