GB1174124A - Pharmacologically Active Indolizine Compounds - Google Patents

Abstract

1,174,124. Indolizine derivatives. BEECHAM GROUP Ltd. 30 Sept., 1968 [30 June, 1967], No. 30271/67. Heading C2C. The invention comprises compounds of formula wherein R<SP>1</SP> is H, a non-toxic metal ion, ammonium, quaternary ammonium or protonated amine group, or a (possibly substituted) hydrocarbon group, R<SP>2</SP> is H, alkyl, aryl or aralkyl, R<SP>3</SP> is H, alkyl, aryl, aralkyl or acyl, and X is H, alkyl or alkoxy. These compounds are prepared by reacting 1-unsubstituted indolizines (except where R<SP>3</SP>=H) with CH 2 O+HNMe 2 to give the corresponding 1-dimethylaminomethylindolizines, converting these to the methohalides, reacting the latter with KCN to obtain the 1-cyanomethylindolizines and hydrolysing the latter with alkali; in the hydrolysis stage indolizine-1- acetamides may also be isolated. Esters may be obtained by reacting the acids with CH 2 N 2 , or the acid Na salt with (e.g.) Et 2 NC 2 H 4 Cl. The compounds where R<SP>3</SP>=H are made by substituting the 1-position of a 3-acylindolizine and thereafter hydrolysing off the acyl group with acid. Starting materials.-Indolizines unsubstituted in the 1- and 3-positions are prepared by cyclizing 1 - R<SP>2</SP>COCH 2 - 2 - methylpyridinium halides with NaHCO 3 , and the products may be acylated in the 3-position to give the corresponding 3-acylindolizines. Therapeutic compositions for parenteral, oral or topical use comprise indolizines of the above formula, which have analgesic and antiinflammatory activity.