SUBSTITUTED OXIMES, HYDRAZONES AND OLEFINS AS NEUROKININ ANTAGONISTS

摘要

Compound represented by structural formula (I) or a pharmaceutically acceptable salt thereof, wherein: a is 0, 1, 2 or 3; b, d and e are independently 0, 1 or 2; R is H, C1-6 alkyl, -OH or C2-C6 hydroxyalkyl; A is an optionally substituted oxime, hydrazone or olefin; X is a bond, -C(O)-, - O- , -NR6-, -S(O)e-, -N(R6)C(O)-, -C(O)N(R6)-, -OC(O)NR6-, -OC(=S)NR6-, - N(R6)C(=S)O-, -C(=NOR1)-, -S(O)2N(R6)-, -N(R6)S(O)2-, -N(R6)C(O)O- or -OC(O) -; T is H, phthalimidyl, aryl, heterocycloalkyl, heteroaryl, cycloalkyl or bridged cycloalkyl; Q is -SR6, -N(R6)(R7), -OR6, phenyl, naphthyl or heteroaryl; R6a, R7a, R8a, R9a, R6 and R7 are H, C1-6 alkyl, C2-C6 hydroxyalkyl, C1-C6 alkoxy-C1-C6 alkyl, phenyl or benzyl; or R6 and R7, together with the nitrogen to which they are attached, form a ring; R9a is R 6 or -OR6; Z is morpholinyl, optionally N-substituted piperazinyl, optionally substituted (a), or substituted (b); g is 0-3 and h is 1-4, provided the sum of h and g is 1-7; wherein aryl, heterocycloalkyl, heteroaryl, cycloalkyl an d bridged cycloalkyl groups are optionally substituted; methods of treating asthma, cough, bronchospasm, inflammatory diseases, and gastrointestinal disorders with said compounds, and pharmaceutical compositions comprising sa id compounds are disclosed.