SUBSTITUTED AMIDES AS TACHYKININ ANTAGONISTS

摘要

A class of substituted amide compounds of formula (I), are antagonists of tachykinins, especially substance P, and are therefore of use in the treatment or prevention of physiological disorders associated with an excess of tachykinins, such as inflammation, pain, migraine and emesis. In formula (I) Ar?1 and Ar2¿ each independently represents a phenyl group optionally substituted by one, two or three groups selected from halo, C¿1-6?alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkylC1-4alkyl, trifluoromethyl, cyano, nitro, SR?a, SORa, SO¿2R?a, ORa, NRaRb, NRaCORb, NRaCO¿2Rb, CO2Ra or CONRaRb, wherein R?a and Rb¿ are each independently H, C¿1-6?alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkylC1-4alkyl, phenyl or trifluoromethyl; Q represents Ar?1¿ or a group of formula Het-(CH¿2?)n-, where n is 1 or 2 and Het is a five or six membered nitrogen containing heterocyclic group with 1, 2 or 3 heteroatoms selected from nitrogen, oxygen or sulphur with at most one oxygen or sulphur atom, which group may have the residue of a further 5 or 6 membered aromatic ring fused thereto, and which group may be optionally substituted by a group selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, oxo, thioxo, halo, cyano, nitro, trifluoromethyl, trimethylsilyl, OR?c, SRc, SORc, SO¿2R?c, NRcRd, NRcCORd, NRcCO¿2Rd, CO2R?c, CONRcRd¿ or phenyl optionally substituted by 1, 2 or 3 groups selected from C¿1-6?alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, halo, cyano, nitro, trifluoromethyl, trimethylsilyl, OR?c, SRc, SORc, SO¿2R?c, NRcRd, NRcCORd, CO¿2Rc, or CONRcRd, where R?c and Rd¿ are each independently H, C¿1-6?alkyl, trifluoromethyl or phenyl; X represents a -CO-NR- or -NR-CO- group, where R is hydrogen, C1-6alkyl, or methyl substituted by a C2-6alkenyl or C2-6alkynyl group; one of Y?1 and Y2¿ is a bond or C¿1-4?alkylene group and the other is a C1-4alkylene group; with the proviso that when Ar?1¿ and Q are dimethoxyphenyl, -Y?1-X-Y2-Ar2¿ is not -CH¿2?CON(CH3)CH2C6H5.