INDAZOLE-3-CARBOXYLIC AMIDES

• Main Authors: LASZLO MAGDANYI, PETER GOROG, LASZLO PALLOS, LUJZA ERDELYI, ANDRAS GELLERI
• Format: Patent
• Language: English
• Published: 05.12.1972
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

1301882 Indazole derivatives EGYT GYOGYSZERVEGYESZETI GYAR 31 March 1970 [1 April 1969] 15218/70 Heading C2C The invention comprises the novel 5,6-dimethoxylH-indazole derivatives of the formula wherein R1 and R2 each are H, C 1-16 alkyl, cycloalkyl or naphthyl or phenyl or aralkyl, optionally substituted by one or two C 1-4 alkyl, C 1-4 alkoxy, CF 3 radicals or halogen atoms, or together with the adjacent nitrogen atom form a 5 or 6 membered saturated heterocyclic ring, optionally containing a further N atom which may be substituted by C 1-4 alkyl, and Q is H, alkali metal atom or C 1-5 aliphatic aryl and their preparation. The compounds are prepared by reacting amides of the Formula II wherein R 3 is NH 2 or acid addition salts thereof with compounds of the formula R4ONO, wherein R4 is H or C 1-5 alkyl, or by reacting 5,6-dimethoxy-1H-indazole-3-carboxylic acid or ester thereof, or 2,3,9,10-tetramethoxy-7H,14H-diindozolo[2,3a,21,31d]pyrazine - 7,14 - dione with amines of the formula HNR1R2, and, if desired, converting the compounds thus obtained in which Q is H into alkali metal salts or N-acyl derivatives. Compounds of the above formula in which Q, R1 and R2 are H may be obtained by the hydrolysis of the corresponding nitrile. Ethyl 5,6 - dimethoxy - 1H - indazole - 3- carboxylate is prepared by reacting ethyl 2- amino - 4,5 - dimethoxy - phenylacetate with sodium nitrite in the presence of cone. hydrochloric acid, or by esterifying, 5,6-dimethoxy- 1H - indazole - 3 - carboxylic acid, obtained by hydrolysing 5,6 - dimethoxy - 1H - indazole- 3-carboxamide. The free acid may also be obtained by hydrolysing the ethyl ester. 5,6 - Dimethory - 1H - indazole - 3 - carboxylic acid chloride is made by reacting the corresponding acid with thionyl chloride. 5,6 - Dimethoxy - 1H - indazole - 3 - carbonitrile is prepared by reacting 2-amino-4,5-dimethoxyphenylacetonitrile with sodium nitrite in the presence of cone. hydrochloric acid. Pharmaceutical compositions, suitable for oral or parenteral administration, contain the above noval compounds in admixture with physiologically compatible carriers or excipients. The compounds possess anti-inflammatory, antipyretic, analgesic and anti-peristaltic activities. They also inhibit gastric and saliva secretion.