QUINOLINE-4-CARBOXAMIDE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS NEUROKININ 3 (NK-3)- AND NEUROKININ 2 (NK-2) RECEPTOR ANTAGONISTS.

摘要

A compound of formula (I), or a salt thereof, or a solvate thereof, wherein, Ar is an optionally substituted aryl or a C5-7 cycloalkdienyl group, or an optionally substituted single or fused ring aromatic heterocyclic group; R is C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkylalkyl, optionally substituted phenyl or phenyl C1-6 alkyl, an optionally substituted five-membered heteroaromatic ring comprising up to four heteroatoms selected from O and N, hydroxy C1-6 alkyl, amino C1-6 alkyl, C1-6 alkylaminoalkyl, di C1-6 alkylaminoalkyl, C1-6 acylaminoalkyl, C1-6 alkoxyalkyl, C1-6 alkylcarbonyl, carboxy, C1-6 alkoxycarbonyl, C1-6 alkoxycarbonyl C1-6 alkyl, aminocarbonyl, C1-6 alkylaminocarbonyl, di C1-6 alkylaminocarbonyl, halogeno C1-6 alkyl; or R is a group -(CH2)p- wherein p is 2 or 3 which group forms a ring with a carbon atom of Ar; R1 represents hydrogen or up to four optional substituents selected from the list consisting of: C1-6 alkyl, C1-6 alkenyl, aryl, C1-6 alkoxy, hydroxy, halogen, nitro, cyano, carboxy, carboxamido, sulphonamido, C1-6 alkoxycarbonyl, trifluoromethyl, acyloxy, phthalimido, amino or mono- and di-C1-6 alkylamino; R2 represents hydrogen, C1-6-alkyl, hydroxy, halogen, cyano, amino, mono- or di-C1-6-alkylamino, alkylsulphonylamino, mono- or di-C1-6-alkanoylamino wherein any alkyl group is optionally substituted with an amino group or with a mono- or di-alkylamino group, or R2 is a moiety -X-(CH2)n-Y wherein X is a bond or -O- and n is an integer in the range of from 1 to 5 providing that when X is O-n is only an integer from 2 to 5 and Y represents a group NY1Y2 wherein Y1 and Y2 are independently selected from hydrogen, C1-6-alkyl, C1-6-alkenyl, aryl or aryl-C1-6-alkyl or Y is hydroxy, halogen or an optionally substituted N-linked single or fused ring, heterocyclic group, R3 is branched or linear C1-6 alkyl, C3-7 cycloalkyl, C4-7 cycloalkylalkyl, optionally substituted aryl, or an optionally substituted single or fused ring aromatic heterocyclic group; and R4 represents hydrogen or C1-6 alkyl.