Quinoline derivatives as NK3 antagonists

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):

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• 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 hetero-atoms in the or each ring selected from S, O, N;
• R is linear or branched C1-8 alkyl, C3-7 cycloalkyl, C4-7 cycloalkylalkyl, optionally substituted phenyl or phenyl C1-6 alkyl, an optionally substituted five-membered heteroaromatic ring comprising up to four heteroatom 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 alkoxyxcarbonyl, C1-6 alkoxycarbonyl C1-6 alkyl, aminocarbonyl, C1-6 alkylaminocarbonyl, di C1-6 alkylaminocarbonyl, halogeno C1-6 alkyl;
• 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, C1-6 alkenyl, aryl, C1-6 alkoxy, hydroxy, halogen, nitro, cyano, carboxy, carboxamido, sulphonamido, C1-6 alkoxycarbonyl, trifluoromethyl, acyloxy, phthalimido, amino, mono- and di-C1-6 alkylamino. —O(CH2)r—NT2. in which r is 2, 3, or 4 and T is hydrogen or C1-6 alkyl or it forms with the adjacent nitrogen a group
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• 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 C1-6 alkyl;
• 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 C1-6 alkyl, C3-7 cycloalkyl, C4-7 cycloalkylalkyl, 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 hetero-atoms in the or each ring selected from S, O, N;
• X is O, S, or N—C≡N.