Patent FR-2100682-B1 (FR)
IPC: C07D499/64
Filed: 1971-05-25
Granted: 1975-01-17
Abstract: 1301962 Ureido penicillins BAYER AG 25 May 1971 [25 May 1970 1 Feb 1971 3 Feb 1971] 16881/71 Heading C2A  The invention comprises penicillins of the general Formula (I) in which general formula A is a group having one of the general formulµ (2), (3) or (4) in which formulµ X is a hydrogen atom or an alkyl, alkenyl, cycloalkyl or cycloalkenyl group with up to ten carbon atoms, or a vinyl, arylvinyl, mono-, di- or tri-haloalkyl, alkyamino, dialkylamino, monoarylamino, arylalkylamino or aryloxy group or an alkoxy or aryloxy group, or an alkoxy or aryloxy group with up to 8 carbon atoms, or a cycloalkoxy group with up to 7 carbon atoms, or a group having one of the general formulµ (lower alkyl)-O-V-, (lower alkyl)-S-V-, N#C-V-,(lower alkyl)-O-CO-V- or in which formulµ V is a bivalent organic radical with 1 to 3 carbon atoms, lower alkyl groups have up to six carbon atoms; n is 0, 1 or 2 and R 1 , R 2  and R 3  may be the same or different and are each hydrogen, chlorine, bromine, iodine or fluorine, nitro, nitrile, di(lower alkyl)amino, di(lower alkyl)ammo-carbonyl, lower alkanoylamino, lower alkoxy carbonyl, lower alkanoyloxy, lower alkyl, lower alkoxy, sulphamyl or trifluoromethyl; Y is an alkyl, alkenyl, cycloalkyl or cycloalkenyl group with up to 10 carbon atoms, or a vinyl, propenyl, mono-, di- or tri-halo (lower alkyl) aryl or heterocyclic group, or an aralkyl group with up to 8-carbon atoms; #Z- is a divalent group having one of the formulµ in which formulµ n is 3, 4 or 5 and the arrow # means that the two free valencies of the group Z are not arbitrarily joined to the N and C atoms of the group (3) but are oriented as indicated by the arrow. Q is a divalent group, B is a group having one of the general formulµ in which formulµ R 4 , R 5  and R 6  may be the same or different and are each hydrogen, halogen, lower alkyl, lower alkoxy, lower alkylthio, lower alkylthionyl, lower alkylsulphonyl, nitro, di(lower alkyl) amino, lower alkanoylamino, hydroxy, or lower alkanoyloxy and in which the chirality centre C*can have either of the two possible R and S stereoisomeric configurations or can be a mixture of these two diastereosiomers. The invention also comprises salts of the above penicillins. A process for the production of penicillins of Formula (I) comprises reacting 6-amino-penicillanic acid or a compound of the general formula (46) or (47) in which R 7 , R 8  and R 9  are the same or different alkyl groups having up to 6 carbon atoms, at a temperature of -30‹ C. to +50‹ C. with a carboxylic acid of general formula If compounds of formula (46) or (47) are used, the reaction is carried out in an anhydrous solvent which is free of hydroxyl groups, with or without a base, and if 6-aminopenicillanic acid is used, the reaction is carried out in a solvent in the presence of a base. Various modifications of the process are described. Antibiotically active pharmaceutical compositions, which contain as active ingredient at least one penicillin of Formula (I) or a pharmaceutically acceptable salt thereof, have been prepared. Such compositions also contain a pharmaceutically acceptable carrier which may be solid or liquid. These compositions may be adapted for parenteral or oral administration and may be prepared in dosage unit form.