GB965511A - Improvements in or relating to 3-aminoindazole derivatives - Google Patents

Abstract

The invention comprises compounds of general formula: <FORM:0965511/C1/1> (wherein R1 may alternatively be in the 2-position), in which R is bromine, chlorine, fluorine or trifluoromethyl and is in a position b to the hetero-ring, R1 is hydrogen, lower (1-6 C) alkyl or phenyl, and R2 and R3 are hydrogen or lower alkyl (including various polymorphic forms thereof); non-toxic pharmaceutically acceptable acid addition salts thereof; and their preparation as described, comprising (1) reaction of an R-substituted-o-halo-benzonitrile with a compound of formula H2N.NHR1; (2) diazotisation of an R-substituted -o-cyano-aniline with hydrochloric acid and sodium nitrite and treatment of the diazo compound with stannous chloride in hydrochloric acid; (3) formation of monomethylamino compounds by reacting the amine with methyl or ethyl formate and treating the N-formyl compound with a metallic hydride; (4) formation of dimethylamino compounds by reacting the amine with aqueous formaldehyde and formic acid; (5) formation of mono- or di-alkylamino compounds by reacting an R-substituted-o-halobenzonitrile with a lower alkanol using hydrogen chloride, reacting the imino-ether with an amine HNR2R3, and condensing the o-halo-benzamidine with a hydrazine H2N.NHR1; (6) N-methylation of the indazole ring using dimethyl sulphate. 2-Bromo-5-trifluoromethyl-benzonitrile is prepared by the action of cuprous cyanide solution on the corresponding diazonium salt; 2-nitro-4-trifluoromethyl-benzonitrile, 4-chloro-2-iodo-benzonitrile and 5-bromo-2-nitro-benzonitrile are prepared similarly. 4-Fluoro-2-iodo-aniline is prepared by iodination, and on treatment with cuprous cyanide yields 2-cyano-4-fluoro-aniline. 2-Cyano-5-trifluoromethylaniline and 4-bromo-2-cyano-aniline are prepared by reduction of the corresponding nitro compounds. Pharmaceutical compositions comprise compounds I and their pharmaceutic acceptable acid addition salts together with pharmaceutical carriers. Oral and parenteral administration using solid (tablets, powders, capsules, troches, lozenges) and liquid (capsules, ampoules, suspensions) preparations is mentioned. The compounds have muscle relaxant, tranquillizing, analgesic and antipyretic action.