COMPOUNDS USEFUL IN PAIN RELIEF WHICH CONTAIN METHYLENEAMINO AND OXY LINKING GROUPS, PROCESS FOR PREPARING THEM, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND THEIR USES FOR THE PREPARATION OF PHARMACEUTICAL COMPOSITIONS

摘要

Pain relieving compounds of the formula wherein: A is an optionally substituted: phenyl, naphthyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidiyl, thienyl, thiazolyl, oxazolyl or thiadiazolyl having at least two adjacent ring carbon atoms; provided that 3103 ח' בטבת התשס" ב - December 23, 2001 the -CH(R3)N(R2)B-R1 and -OR4 groups are positioned in a 1,2-relationship to one another on ring carbon atoms and the ring atom positioned ortho or the OR4 linking group (and therefore in the 3-position relative to the -CHR3NR2-linking group) is not substituted; B is an optionally substituted: phenyl, pyridyl, thiazolyl, thienyl, thiadiazolyl, imidazolyl, pyrazinyl, pyridazinyl or pyrimidyl; R1 is positioned on ring B in a 1,3 or 1,4 relationship with the -CH(R3)N(R2)- linking group and is carboxy, carboxy (C1-3 alkyl, tetrazolyl, tetrazolyl C1-3 alkyl, tetronic acid, hydroxamic acid radical, sulphonic acid radical, or R4 is of the formula -CONRaRal wherein Ra is hydrogen or C1-6 alkyl and Ra1 is hydrogen, C1-6 alkyl (optionally substituted by halo, amino, C1-4 alkylamino, di-C1-4 alkylamino, hydroxy, nitro, cyano, trifluoromethyl, C1-4 alkoxy or C1-4 alkoxycarbonyl), C2-6 alkenyl (provided the double bond in not in the 1-position), C2-6 alknyl (provided the triple bond is not in the 1-position), carboxyphenyl, 5- or 6-membered heterocyclyl C1-3 alkyl, 5- or 6-membered heteroaryl C1-3 alkyl, 5- or 6-membered heterocyclyl, or 5- or 6-membered heteroaryl or Ra and Ral together with the amide nitrogen to which they are attached (NRaRal) form an amino acid residue or ester thereof, or R1 is of the formula -CONHSO2Rb wherein Rb is C1-6 alkyl (optionally substituted by halo, hydroxy, nitro, cyano, trifluoromethyl, C1-4 alkoxy, amino, C1-4 alkylamino, di-C1-4 alkylamino or C1-4 alkoxycarbonyl), C2-6 alkenyl (provided the double bond is not in the 1-position), C2-6 alkynyl (provided the triple bond is not in the 1-position), 5- or 6-membered heterocyclyl C1-3 alkyl, 5- or6-membered heteroaryl C1-3 alkyl, phenyl C1-3 alkyl, 5- or 6-membered heterocyclyl, 5- or 6-membered heteroaryl or phenyl; wherein any heterocyclyl or heteroaryl group in Ra1 is optionally substituted by halo, hydroxy, nitro, cyano, trifluoromethyl, C1-4 alkoxy or C1-4 alkoxycarbonyl and any phenyl, heterocyclyl or heteroaryl group in Rb is optionally substituted by halo, trifluoromethyl, nitro, hydroxy, amino, cyano C1-6 alkoxy, C1-6 alkylS(O)p- (p is 0, 1 or 2), C1-6 alkyl, carbamoyl, C1-4 alkylcarbamoyl, di(C1-4 alkyl) carbamoyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 alkoxycarbonylamino, C1-4 alkanoylamino, C1-4 alkanoyl (N-C1-4 alkyl) amino, C1-4 alkanesulphonamido, benzenesulphonamido, aminosulphonyl, C1-4 alkylaminosulphonyl, di(C1-4 alkyl) aminosulphonyl, C1-4 alkoxycarbonyl, C1-4 alkanoyloxy, C1-6 alkanoyl, formyl C1-4 alkyl, hydroxyimino C1-6 alkyl, C1-4 alkoxyimino C1-6 alkyl or C1-6 alkylcarbamoylamino; or R1 is of the formula -SO2N(R!)R!l wherein R! is hydrogen or C1-4 alkyl and R!i is hydrogen or C1-4 alkyl; or R1 is of the formula (IA), (IB) or (IC); wherein X is CH or nitrogen, Y is oxygen or sulphur, Y( is oxygen or NRd and Z is CH2, NRd or oxygen provided that there is no more than one ring oxygen and there are at least two ring heteroatoms and wherein Rd is hydrogen or C1-4 alkyl; R2 is hydrogen, C1-6 alkyl, optionally substituted by hydroxy, cyano or trifluoromethyl, C2-6 alkenyl (provided the double bond is not in the 1-position). 3104 ח' בטבת התשס" ב - December 23, 2001