GB1368716A - Cephalosporin compounds - Google Patents

Abstract

1368716 α-Sulphoacylamino-cephalosporins TAKEDA YAKUHIN KOGYO KK 28 July 1972 [29 July 1971] 35475/72 Addition to 1300692 Heading C2A Novel α-sulphoacylamino-cephalosporins having the Formula (I) and salts thereof, wherein R<SP>1</SP> is hydrogen or an aliphatic, aromatic or heterocyclic group and R<SP>2</SP> is a heterocyclic group are prepared by either (a) reacting a corresponding α-sulphoacylaminocephalosporanic acid (or a derivative thereof wherein the acetoxy group in the 3-acetoxymethyl group is replaced by a group which is similarly capable of nucleophilic replacement by a heterocyclic thiol group) with a heterocyclic thiol of formula R<SP>2</SP>SH; or (b) acylating a corresponding 3 - heterocyclic - thiomethyl - 7- aminocephalosporanic acid with the appropriate α-sulphocarboxylic acid or an N-acylating derivative thereof. The group R<SP>2</SP> may be a 5- or 6- membered monocyclic or fused heterocycle containing one to three hetero atoms selected from N, S and O, e.g. a pyrimidine, pyridine, tetrazole, thiazole or thiadiazole ring, optionally substituted, e.g. by NO 2 , NH 2 , SH, Cl, Br, CH 3 or C 2 H 5 , and/or partly saturated. The nitrogen atom may be quaternary. The group R<SP>1</SP> may be C 1 -C 10 alkyl, phenyl or substituted (e.g. halo) phenyl, tolyl, naphthyl or thienyl. Groups capable of nucleophilic displacement at the 3- position include halogen, thiol, hydroxy, acyloxy and substituted acyloxy groups. The N- acylating derivatives of the acid are typically the halides, acid anhydrides, active esters and azides. Reaction (a) is preferably carried out in a polar solvent at alkaline pH in the presence of potassium thiocyanate. Acid reactants may be used in the form of their salts or easily decomposable esters. Pharmaceutical compositions having antibiotic activity against Gram-positive and Gramnegative bacteria comprise a cephalosporin of Formula (I) or a non-toxic salt thereof and a pharmaceutically acceptable carrier or diluent.