IE39444L - Phthalazine derivatives. - Google Patents

Abstract

1398549 Phthalazine derivatives and their use in pharmaceutical compositions BOOTS CO Ltd 6 Nov 1973 [6 Nov 1972] 50973/72 Heading C2C Compounds of the formula or its enol or enthiol form of the formula wherein Q is COOH, CH 2 OH or COOR 6 , where R 6 is an ester forming group, X is oxygen or sulphur, R is hydrogen or alkyl, Z is hydrogen or acyl, and Ar is a phenyl group unsubstituted in the ortho positions and which may have one or more substituents, or to which an optionally substituted mono- or polycyclic is fused, which ring or rings may contain one or more hetero atoms; or pharmaceutically acceptable salts thereof with inorganic or organic bases, may be prepared by conventional methods. Compounds of the above formulµ with the proviso that when (i) Q is COOH, COOMe or COOEt, X is oxygen, and R is hydrogen or methyl, then Ar is not phenyl, m- or p-chlorophenyl, m- or p-nitrophenyl, p-(p-nitrophenylazo)phenyl or p-phenylazophenyl, or (ii) when Q is COOH, X is oxygen and R is hydrogen, then Ar is not m- or p-anilino or m- or p-acetamido phenyl, are claimed to be novel. Preferred compounds in which the radical Ar has the formula wherein R 3 , R 4 and R 5 are the same or different and are selected from hydrogen, halogen, nitro, nitroso, cyano, isocyano, carboxy, optionally substituted amino, optionally substituted alkyl, optionally substituted cycloalkyl, alkenyl, aryl, cycloalkenyl, optionally substituted alkoxy, alkenyloxy, cycloalkoxy, cycloalkenyloxy, acyloxy, optionally substituted alkylthio, alkenylthio, cycloalkylthio, cycloalkenylthio, arylthio, alkylsulphonyl, alkylsulphinyl, optionally substituted acyl, aryl, heteroaroyl, hydroxy, mercapto, carbamoyl, thiocarbamoyl, optionally substituted sulphamoyl, optionally substituted heterocyclic rings, or R 3 and R 4 together form a portion of a carbocyclic or heterocyclic ring fused to the benzene ring, which rings may be substituted, may be prepared, for example, by a process which comprises the steps of (a) reacting a salt of 2-naphthol-1-sulphonic acid with a compound of the formula wherein R 2 is hydrogen, iodine, bromide or chlorine and Y is the anion of a mineral acid, (b) treating the product from (a) with a mild base, (c) treating the product from (b) with an alkali metal hydroxide, followed by acidification to give a compound of the formula (d) optionally modifying at least one of the groups R 3 , R 4 or R 5 and/or, if R 2 is iodine, bromine or chlorine, converting it to hydrogen, and/or converting the 1-acetic acid group to a hydroxyethyl group, (e) treating the product from (c) or (d) with an aqueous acid or an alcoholic acid to give a compound of the formula in which R is hydrogen and X is oxygen, (f) in the case where R 2 is iodine, bromine, or chlorine, converting it to hydrogen, (g) in the case when the compound obtained from (d), (e) or (f) is one falling within the proviso, modifying at least one of the groups Q, X, Z, R, R 3 , R 4 or R 5 , to give a compound not falling within the proviso, (h) modifying at least one of the groups in the product obtained from (e), (f) or (g), and (i) optionally forming a pharmaceutically acceptable salt with an organic or inorganic base of any compound which is an acid. The products possess pharmaceutical properties and they may be formulated and applied in a conventional manner. [GB1398549A]