Patent ZA-846606-B (ZA)
Title: Cephalosporin derivatives and a process for their preparation
Inventor: FLEISCHMANN KLAUS
IPC: A61K31/545
Filed: 1984-08-24
Abstract: for the Contracting States : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE 1. A cephem derivative of the formula I  see diagramm : EP0135142,P13,F1  and its physiologically acceptable acid addition salts, in which R**1 denotes hydrogen, R**2 denotes C1 -C4 -alkyl which is monosubstituted to hexasubstituted by fluorine, A denotes a pyridinium radical  see diagramm : EP0135142,P13,F2  which can be substituted by C3 -C6 -cycloalkyl or by 2 alkyl groups in ortho positions which are linked to form a trimethylene to pentamethylene ring in which a ring carbon atom can be replaced by an oxygen or sulfur atom and which can, at the same time as the oxygen or sulfur atom, additionally contain a double bond and in which the R**2O groups is in the syn-position. for the Contracting State : AT 1. A process for preparing a cephem derivative of the formula I  see diagramm : EP0135142,P15,F1  and its physiologically acceptable acid addition salts, in which R**1 denotes hydrogen, R**2 denotes C1 -C4 -alkyl which is monosubstituted to hexasubstituted by fluorine, A denotes a pyridinium radical  see diagramm : EP0135142,P15,F2  which can be substituted by C3 -C6 -cycloalkyl or by 2 alkyl groups in ortho positions which are linked to form a trimethylene to pentamethylene ring in which a ring carbon atom can be replaced by an oxygen or sulfur atom and which can, at the same time as the oxygen or sulfur atom, additionally contain a double bond and in which the R**2O groups is in the syn-position, which comprises a) reacting a compound of the formula II  see diagramm : EP0135142,P15,F3  or its salts or a reactive derivative of the compound II in which R**1 and R**2 have the abovementioned meanings and R**3 denotes an amino or a protected amino group, and R**4 denotes a group which can be replaced by those bases which correspond to the radicals A of the formula I, with these bases and alpha) splitting off any protective group present and beta) if necessary, converting the product obtained into a physiologically acceptable acid addition salts, or b) reacting a compound of the formula III  see diagramm : EP0135142,P15,F4  in which R**4 has the meaning mentioned in formula II and R**5 denotes an amino group or a protected amino group, or its reactive derivatives, with the base from which the radical A defined in formula I is derived, to form a compound of the formula IV  see diagramm : EP0135142,P16,F5  in which R**5 and A have the abovementioned meanings, splitting off any amino-protecting group present and reacting the compound IV in which R**5 denotes an amino group, either as such or in the form of an acid addition salt or of a reactive derivative, with a 2-(2-aminothiazol-4-yl)-2-syn-oxyiminoacetic acid of the formula V see diagramm : EP0135142,P16,F6  in which R**1, R**2 and R**3 have the abovementioned meanings, or with a derivative of this compound which is activated at the carbonyl group, and alpha) splitting off any protective group present and beta) if necessary, converting the product obtained into a physiologically acceptable acid addition salt.