The present invention relates to compounds of formula (I) ##STR1## wherein X is --NR.sup.6 R.sup.7 or C-- or N-linked imidazolyl; Y is hydrogen or C.sub.1-4 alkyl optionally substituted by hydroxy; R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are selected from a variety of suitable aromatic substituents; R.sup.6 is hydrogen, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkylC.sub.1-4 alkyl, phenyl, or C.sub.2-4 alkyl substituted by C.sub.1-4 alkoxy or hydroxy; R.sup.7 is hydrogen, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl C.sub.1-4 alkyl, phenyl, or C.sub.2-4 alkyl substituted by one or two of C.sub.1-4 alkoxy, hydroxy or a 4, 5 or 6 membered heteroaliphatic ring containing one or two heteroatoms selected from N, O and S; or NR.sup.6 R.sup.7 is a saturated or partially saturated heterocyclic ring of 4 to 7 ring atoms, optionally containing one of O, S, NR.sup.8, S(O) or S(O).sub.2 and optionally substituted by one or two of hydroxy.sub.1-4 alkyl, C.sub.1-4 alkoxy C.sub.1-4 alkyl, oxo, COR.sup.a or CO.sub.2 R.sup.a ; or NR.sup.6 R.sup.7 forms a non-aromatic azabicyclic ring system of 6 to 12 ring atoms; and R.sup.9a and R.sup.9b are each independently hydrogen or C.sub.1-4 alkyl, or R.sup.9a and R.sup.9b are joined so, together with the carbon atoms to which they are attached, there is formed a C.sub.5-7 ring; or a pharmaceutically acceptable salt thereof. The compounds are of particular use in the treatment or prevention of pain, inflammation, migraine, emesis and postherpetic neuralgia.
A compound having the general formula (I): R.sup.1 R.sup.2 N--CH.sub.2 CH.sub.2 --CHAr.sup.1 --CH.sub.2 --NR.sup.3 --CO--R.sup.4 wherein: R.sup.1 is hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, aryl, C.sub.1-6 alkanoyl C.sub.1-6 alkoxycarbonyl or arylcarbonyl; any of such groups being optionally substituted; R.sup.2 is hydrogen or C.sub.1-6 alkyl; or R.sup.1 or R.sup.2 are joined to form an optionally substituted morpholino ring; Ar.sup.1 is phenyl mono- or di-substituted by halo; R.sup.3 is hydrogen or C.sub.1-6 alkyl; R.sup.4 is optionally substituted naphth-1-yl; or pharmaceutically acceptable salts thereof. These compounds antagonize the pharmacological actions of the endogenous neuropeptide tachykinins, particularly the neurokinin 1 (NK1) receptor.
Compounds having the general formula wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and Ar are as defined in the specification, methods of making such compounds, methods of using such compounds for the treatment of diseases and pharmaceutical compositions comprising such compounds.
A compound having the general formula and methods of using such compounds for the treatment of diseases and pharmaceutical composition comprising such compounds.
The compounds of formula I are useful in treating gastrointestinal disorders associated with antagonizing the motilin receptor. The compounds compete with erythromycin and motilin for the motilin receptor. In addition the compounds are antagonists of the contractile smooth muscle response to those ligands.
The compounds of formula I are useful in treating gastrointestinal disorders associated with antagonizing the motilin receptor. The compounds compete with erythromycin and motilin for the motilin receptor. In addition the compounds are antagonists of the contractile smooth muscle response to those ligands.
