GB1392849A - Penicillins their production and their medicinal use - Google Patents

Abstract

1392849 Penicillins BAYER AG 23 Oct 1972 [23 Oct 1971 22 Nov 1971 25 March 1972 25 July 1972] 48699/72 Heading C2C [Also in Division C3] Penicillins of the general formula or their salts in which C* is a carbon atom constituting a centre of chirality; A is a radical of one of the general formulµ (in which general formulµ X is Y is Q 1 is or a radical of formula and Q 2 is or a radical of formula wherein R is a straight-chain or branched alkyl radical with up to 5 carbon atoms; R 1 is a hydrogen atom or an alkyl, cycloalkyl, alkenyl or cycloalkenyl radical with up to 10 carbon atoms, or a vinyl, arylvinyl, mono-, di- or trihalo C 1-6 alkyl radical, or an H 2 N-, R-NH-, (R) 2 =N-, aryl -NH-, or aryl C 1-6 alkylamino radical or an alkoxy*, or aralkoxy* radical with up to 8 carbon atoms, or a cycloalkoxy* radical with up to 7 carbon atoms, or an aryloxy*, R-O-V-, R-S-V-, (R) 2 =N-CO-V- or a radical of formulµ V is a divalent organic radical with 1 to 3 carbon atoms; n is 0, 1, or 2; R 2 and R 3 which may be the same or different are each a hydrogen atom or an alkyl or alkenyl radical having up to 8 carbon atoms or a vinyl, allyl or propenyl radical, or a cycloalkyl or cycloalkenyl radical having up to 6 carbon atoms; or a mono di-, or tri-halogeno C 1-6 alkyl or aryl radical; R 4 , R 5 and R 6 which may be the same or different are each a hydrogen, nitro, nitrile, (R) 2 =N-, (R) 2 = N-CO-, R-CO-NH-, R-O-CO-, R-CO-O-, R, R-O, H 2 N-SO 2 -, chlorine, bromine, iodine, fluorine or trifluoromethyl radical; and G is a hydrogen atom or a radical R; with the proviso that the meanings marked* are only available if X is not an -SO 2 - radical); Z is a -CO- or -SO- radical; and B is a radical of the general formula in which R 7 , R 8 and R 9 are identical or different radicals selected from hydrogen, halogen, R-, R-O-, R-S-, R-SO-, R-SO 2 -, nitro(R 2 )=N-, R-CO-NH-, OH, and radicals and R is as above defined; and in which above general formulµ the arrow in the divalent linkage member ##Q 2 means that the linkage of two atoms by the two free valencies of this linking member is not free to take place in either direction but only in the manner indicated by the arrow are prepared by reacting a 6-amino-penicillanic acid derivative of the general formula or a product of the condensation of such a derivative with a carbonyl compound 'of formula or a silyl or disilyl derivative of the derivative of the general formulµ respectively is reacted with a compound of the general formula A-Z-W, in an anhydrous or aqueous solvent in the presence of a base, when a compound of general Formulae XIV and XV is reacted, and in an anhydrous solvent free of hydroxyl groups, with or without a base, when a compound of the general Formulµ XVI and XVII is reacted, at a temperature of - 50‹ to + 50‹ C. (wherein A, C*, G, Q 1 , Q 2 , R 1 , R 2 , X, Y, Z and B are as above defined and R 10 , R 11 and R 12 , which can be the same or different are C 1-6 alkyl and W is halogen, azide or Compounds of the above general formula wherein B is phenyl, cyclohexadienyl or hydroxyphenyl are stated to be novel. Compounds of the formula A-Z-W, and Formulµ XVIII and XIX are prepared by conventional methods. Pharmaceutical compositions having antibacterial activity useful in human and veterinary medicine comprise the above penicillins and a carrier. The compositions may be administered orally, parenterally, rectally or topically in conventional pharmaceutical forms. The following starting materials are also prepared: 3 - acetyl - 3 - (N - methylaminocarbonyl}-, 3 - methoxy - carbonyl, 3 - methylsulphonyl-, 3 - aminocarbonyl-, 3 - dimethylaminocarbonyl-, 3 - isopropoxycarbonyl-, 3 - pyrrolidyl - N- carbonyl-, 3 - piperidyl - N - carbonyl-, 3- phenylaminocarbonyl-, 3 - phenoxycarbonyl-, 3- benzoyl-, 3-furoyl-, 3-butyryl-, -, 3-formyl- 3 - pivaloyl-, 3 - cyclohexyloxycarbonyl-, 3- ethane - sulphonyl-, 3 - propionyl-, 3 - benzenesulphonyl-, 3 - methane - sulphonyl - aminocarbonyl- and 3 - thienyl - 2 - sulphonyl - imidazolidine - 1 - carbonyl chloride and the corresponding N - substituted - imidazolidin - 2- ones; 2 - chlorosulphonylthiophene; 1 - methanesulphonyl - 3 - chlorocarbonyl - 4 or -5 - methylimidazolidine - 2 - one and 1 - methanesulphonyl- 4- or 5 - methylimidazolid - 2 - one; 4 - methylimidazolidin - 2 - one; 1 - chlorocarbonyl - 2- methylsulphonylamino- and 2 - tosylamino - 4,5- dihydroimidazoles; 1 - (methylaminocarbonyl)- 3 - ethoxycarbonyl - guanidine and its N- nitroso derivative, N (1,1 -dioxo-isothiazolidin-2- yl] - carbonyl] - N - methyl - carbamic acid chloride; N - mesyl - N<SP>1</SP> - chlorocarbonylurea; 3- acetyl-, 3 - formyl-, 3 - mesyl-, and 3 - phenyl sulphonyl-, 1 - chlorocarbonyl - 2 - oxo - 1,3- diazacyclohexanes and their 1 -unsubstituted derivatives.