Patent IL-118663-A (IL)
Title: Compounds containing methyleneamino and oxy linking groups which are useful in pain relief, process for preparing them, pharmaceutical compositions containing them and their uses
IPC: C07D237/18
Filed: 1996-06-16
Abstract: A compound of the formula wherein: A is an optionally substituted: phenyl, naphthyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidyl, thienyl, thiazolyl, oxazolyl or thiadiazolyl having at least two adacent ring carbon atoms; provided that the -CR(R3)N(R2)B-R1 and -OD groups are positioned in a 1,2 relationship to one another on ring carbon atoms and the ring atom positioned ortho to the -OD linking group (and therefore in the 3-position 62 ז' באייר התשס" א - April 30, 2001 relative to the -CHR3NR2- linking group) is not substituted; B is an optionally substituted: phenyl, pyridyl, thiazolyl, oxazolyl, 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 R1 is of the formula - CONRaRa1 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 alkynyl (provided the triple bond is not in the 1-position), carboxyphenyl, 5- or 6-membered heterocyclic 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 Ra1 together with the amide nitrogen to which they are attached (NRaRa1) 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, amino, C1-4 alkylamino, di-C1-4 alkylamino, trifluoromethyl, C1-4 alkoxy 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 hetrocyclyl C1-3 alkyl, 5- or 6-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, S(O)pC1-6 alkyl (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(Rc)Rc1 wherein Rc is hydrogen or C1-4 alkyl and Rc1 is hydrogen or C1-4 alkyl; or R1 is of the formula 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 63 ז' באייר התשס" א - April 30, 2001 trifluoromethyl, 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), phenyl C1-3 alkyl or pyridyl C1-3 alkyl; R3 is hydrogen, methyl or ethyl; D is hydrogen, an optionally substituted 5-7 membered carbocyclic ring containing one double bond, C1-3 alkyl substituted by an optionally substituted 5-7 membered carbocyclic ring containing one double bond or D is of the formula - (CH2)nCH(R4)C(R5)=C(R6)R7 wherein: R4 is hydrogen, methyl or ethyl; R5 is hydrogen, methyl, bromo, chloro, fluoro or