SE373142

1,211,694. Cephalosporins. GLAXO LABORATORIES Ltd. 4 Dec., 1967 [15 Dec., 1966], No. 56301/66. Heading C2A. [Also in Division A5] The invention comprises 7 - acylamido - 3 - methyl (or 3-substituted methyl)-ceph-3-em-4- carboxylic acids having an N-linked polyazole ring substituent on the acylamido group at the 7-position and/or on the methyl group at the 3-position, salts and esters thereof; and the corresponding 7-amino compounds. The polyazole ring contains at least three N atoms in the ring. Preferred are the 1-(71-acylamido-41-carboxyceph - 31 - em - 31 - yl methyl) - 1,2,3- triazoles and -1,2,3-triazolines and particularly triazolines of Formula III wherein R is H or acyl and the groups Y are cyano or methoxycarbonyl groups, e.g. 4,5- dimethoxycarbonyl-1-(41- carboxy - 71 - phenylacetamido - ceph - 31 - em - 31- yl methyl)- 1,2,3-thiazole; and salts and esters thereof. The compounds are prepared by reacting a dipolarophile with a cephalosporanic acid, salt or ester, the acid having the Formula II wherein R is H or acyl which may contain an azido group; and X is an acetoxy group, an azido group or H, at least one of R and X providing the compound of Formula II with at least one azido group, to obtain a compound having at least one polyazole ring substituent, whereafter, when R is H, the resulting compound may be acylated. The ester may be a diphenylmethyl, stannyl or silyl ester. The dipolarophiles are substances which react with groups having a dipole and may be classified as (a) acetylenic, i.e. of structure R1C#CR2, where R1 and R2 may be the same or differe group or atom, e.g. H, cyano, ester such methoxycarbonyl or acyl, e.g. benzoyl; (b) ethylenic, i.e. R5.R6C = CR7R8, wherein R5, R6, R7 and R8 may be the same or different and may be H, cyano, ester, e.g. methoxy carbonyl, acyl or carboxy; (c) cyano compounds other than those of (a) and (b) particularly cyanogen and alkoxy carbonyl cyanides. The azide and dipolarophile are reacted in an organic solvent at 15‹ to 150‹ C. A wide range of specific acyl groups for R of Formulµ II and III is listed. The silyl or stannyl ester group is removed by treatment with a compound containing active hydrogen, e.g. water, acidified or basified water, alcohols, phenols, ureas and amides. Specifications 1,012,943, 1,054,806, 1,082,943 and 1,082,962 are referred to.