Patent GB-1455693-A (GB)
Title: 2,3-lower alkylenepenam-3-carboxylic acid derivatives and processes for the preparation thereof
IPC: C07D499/90
Filed: 1973-11-14
Abstract: 1455693 2,3 - Alkylene penan - 3 - carboxylic acid derivatives, their preparation and use FUJISAWA PHARMACEUTICAL CO Ltd 14 Nov 1973 [22 Nov 1972 27 Nov 1972 15 Dec 1972 24 Jan 1973 (2) 2 Aug 1973 (3)] 51759/73 Heading C2C Compounds of the formula wherein R<SP>1</SP> is an amino or substituted amino group, R<SP>2</SP> is a carboxylic or protected carboxylic acid group, R<SP>3</SP> is a C 1-6  alkyl group, R<SP>4</SP> is a C 1-3  alkylene group, and X is -S- or or salts thereof may be obtained by reacting a compound of the formula wherein Y is the residue of an acid, with a base. The reaction is generally carried out by employing equimolar quantities of the base and the starting material in a solvent, or, if the base which is used is a liquid, it may also be used as the solvent. Preferred radicals R<SP>1</SP>, many of which are specified, include (1-halophenylimino - 1 - C 1-6  alkanoylthiomethyl amino, C 1-6  alkoxycarbonylamino, phenyl (C 1-6 ) alkoxycarbonylamino, C 1-6  alkylthio (C 1-6 ) alkanoylamino, phenyl (C 1-6 ) alkanoylamino, phenoxy (C 1-6 ) alkanoylamino, 3-phenylureido, phenylglyoxylamido, phenylthiocarbamoylamino, phenyl and amino substituted C 1-6  alkanoylamino, phenyl and hydroxy substituted C 1-6  alkanoylamino, phenyl and C 1-6  alkoxycarbonylamino substituted C 1-6  alkanoylamino, phenyl and C 1-6  alkanoyloxy substituted C 1-6  alkanoylamino, phenyl and semicarbazono substituted C 1-6  alkanoylamino, halophenylthioureido, phthalimido, C 1-6  alkanoylaminobenzene-sulphonamido, phenyl and halophenoxy substituted C 1-6  alkanoylamino, halophenyl (C 1-6 ) alkanoylamino, 3-halophenyl-5-C 1-6  alkylisoxazol-4-ylcarbonamido, thienyl (C 1-6 ) alkanoylamino, tetrazolyl - C 1-6  - alkanoylamino, thiadiazolyl - C 1-6  alkanoylamino, thiadiazolylthio (C 1-6 ) alkanoylamino and halobenztriazolyl (C 1-6 ) alkanoylamino. The protected carboxy group R<SP>2</SP> may be, for example, an ester, acid amide, acid anhydride or a salt group. Compounds wherein X is may be prepared by oxidizing the corresponding compounds wherein X is -S-, or alternatively compounds wherein X is -S- may be obtained by reduction of the corresponding S-oxides; compounds wherein R<SP>1</SP> is an acylamino moiety may be obtained by acylation of the corresponding amine, the product may be transacylated, e.g. by reaction with an iminohalogenating agent and an iminoetherifying agent, and the protective acyl group may subsequently be removed by conventional methods. When the acylamino radical includes a hydroxy or amino group, these may be protected and freed by known procedures. Compounds of the formula wherein R<SP>5</SP> is an aryl or substituted aryl group, may be obtained by reacting a compound of the formula with semicarbazide or a salt thereof, and compounds of the formula wherein R<SP>6</SP> is an aryl or substituted aryl group and R<SP>7</SP> is an acyl radical, may be prepared by reacting a compound of the formula with an acylating agent under reducing conditions. Protective groups for the radical R<SP>2</SP> may be introduced and subsequently eliminated by known methods. The products possess antimicrobial properties and they may be formulated as pharmaceutical compositions in a conventional manner.