QUINOLINE DERIVATIVES AS NK3 ANTAGONISTS

摘要

A method for the treatment and/or prophylaxis of conditions characterized by overstimulation of the tachykinin receptors, which method comprises the administration to a mammal in need thereof of an effective, non-toxic, pharmaceutically acceptable amount of a compound of formula (I), or a pharmaceutically acceptable solvate thereof, or a pharmaceutically acceptable salt thereof, wherein: Ar is an optionally substituted phenyl, naphthyl or C5-7 cycloalkdienyl group, or an optionally substituted single or fused ring heterocyclic group, having aromatic character, containing from 5 to 12 ring atoms and comprising up to four heteroatoms in the or each ring selected from S, O, N; R is linear or branched C1-8alkyl, C3-7cycloalkyl, C4-7cycloalkylalkyl, optionally substituted phenyl or phenyl C1-6alkyl, an optionally substituted five-membered heteroaromatic ring comprising up to four heteroatoms selected from O and N, hydroxy C1-6alkyl, amino C1-6alkyl, C1-6alkylaminoalkyl, di C1-6alkylaminoalkyl, C1-6acylaminoalkkyl, C1-6alkoxyalkyl, C1-6alkylcarbonyl, carboxy, C1-6alkoxycarbonyl, C1-6alkoxycarbonyl, C1-6alkyl, aminocarbonyl, C1-6alkylaminocarbonyl, di C1-6alkylaminocarbonyl; halogeno C1-6alkyl; or is a group -(CH2)p- when cyclized onto Ar, where p is 2 or 3. R1 and R2, which may be the same or different, are independently hydrogen or C1-6 linear or branched alkyl, or together form a -(CH2)n- group in which n represents 3, 4 or 5; or R1 together with R forms a group -(CH2)q-, in which q is 2, 3, 4 or 5; R3 and R4, which may be the same or different, are independently hydrogen, C1-6 linear or branched alkyl, C1-6alkenyl, aryl, C1-6alkoxy, hydroxy, halogen, nitro, cyano, carboxy, carboxamido, sulphonamido, C1-6alkoxycarbonyl, trifluoromethyl, acyloxy, phthalimido, amino, mono- and di-C1-6alkylamino, -O(CH2)r-NT2, in which r is 2, 3 or 4 and T is hydrogen or C1-6alkyl or it forms with the adjacent nitrogen a group (a) or (b), in which V and V1 are independently hydrogen or oxygen and u is 0, 1 or 2; -O(CH2)s-OW in which s is 2, 3 or 4 and W is hydrogen or C1-6alkyl; hydroxyalkyl, aminoalkyl, mono- or di-alkylaminoalkyl, acylamino, alkylsulphonylamino, aminoacylamino, mono- or di-alkylaminoacylamino; with up to four R3 substituents being present in the quinoline nucleus; or R4 is a group -(CH2)t- when cyclized onto R5 as aryl, in which t is 1, 2 or 3; R5 is branched or linear C1-6alkyl, C3-7cycloalkyl, C4-7cycloalkylalkyl, optionally substituted aryl, or an optionally substituted single or fused ring heterocyclic group, having aromatic character, containing from 5 to 12 ring atoms and comprising up to four heteroatoms in the or each ring selected from S, O, N; X is O, S, or N-CN.