Patent GB-1059562-A (GB)
Title: Derivatives of cephalosporin c
Inventor: COCKER JOHN DEREK
IPC: C07D501/36
Filed: 1962-09-24
Abstract: Relates to 3-methyldithiocarbamates of cephalosporanic acid derivatives of formula <FORM:1059562/C2/1> in which R2 and R3 are each hydrogen or R2 is hydrogen and R3 is acyl or a triarylsubstituted alkyl; or R2 and R3 together form a divalent acyl derived from a dicarboxylic acid; R4 is hydrogen or an aliphatic, araliphatic or aryl group and R5 is aliphatic, araliphatic or aryl; or R4 and R5 together form a divalent group; and non-toxic salts thereof.  The compounds are produced by reacting in a polar medium a compound of formula <FORM:1059562/C2/2> in which R1 is acyl and R2 and R3 have the above meanings; or a salt thereof, with a nucleophilic compound of formula <FORM:1059562/C2/3> in which M is an alkali metal or ammonium and R4 and R5 have the above meanings.  The medium is water or water and a water-miscible solvent such as acetone; the temperature is 15 DEG  to 70 DEG  C. and the solution may be buffered at pH 5.0 to 8.0. Examples relate to the preparation of 7-(benzylthioacetamido) - cephalosporanic acid N,N-dimethyl dithiocarbamate; 7-(allythio-acetamido) cephalosporanic acid N,N-dimethyl-dithiocarbamate; 7 - (n - butylthioacetamido)-cephalosporanic acid N,N-dimethyldithiocarbamate; 7 - (phenylacetamido) - cephalosporanic acid N,N - dimethyldithiocarbamate; 7-(pentanoylamido) - cephalosporanic acid N,N - di -methyldithiocarbamate; 7 - (b  - phenylpropionamido) - cephalosporanic acid N,N - dimethyl dithiocarbamate; 7 - (thienyl - 31 - acetamido) -cephalosporanic acid N,N - dimethyldithiocarbamate; 7 - (thienyl-21-acetamido)-cephalosporanic acid N,N-dimethyldithiocarbamate; and 7 - (phenylacetamido) - cephalosporanic acid piperidino-dithiocarbamate.  Specified salts are the alkali metal salts and salts with amines such as cyclohexylamine. The compounds are active against gram positive and gram negative microorganisms and are more stable in vivo than cephalosporin C. They are formulated into pharmaceutical compositions (see Division A5).ALSO:Pharmaceutical compositions having anti-bacterial activity comprise a carrier and a cephalosporanic acid derivative of formula. <FORM:1059562/A5-A6/1> wherein R2 and R3 are each hydrogen or R2 is hydrogen and R3 is acyl or a triarylsubstituted alkyl; or R2 and R3 together form a divalent acyl derived from a dicarboxylic acid; R4 is hydrogen or aliphatic, aroliphatic or aryl and R5 is aliphatic, araliphatic or aryl; or R4 and R5 together form a divalent group; or a non-toxic salt thereof.  The salt may be an alkali metal salt or a salt with an amine such as cyclohexyl-amine.  Typical active ingredients are 7-(benzylthio acetamide)-cephalosporanic acid, N,N-diemthyl dithiocarbamate; 7-(allylthioacetomido) cephalosporanic acid N,N-dimethyldithiocarbamate; 7-(n-butylthioacetomido)-aphalosporanic acid N,N-dimethyldithio-carbamate; and 7-(phenylacetamido) cephalosporanic acid piperidino dithiocarbomate. The compositions may be oral e.g. tablets or capsules, parenteral e.g. injectable solutions or suspensions, and rectol e.g. suppositories.  Other antibiotics such as penicillin G and/or the tetracyclines may be present.