| abstract |
1334035 Penicillins F HOFFMANN-LA ROCHE & CO AG 20 Jan 1972 [20 Jan 1971] 2825/72 Heading C2A Novel penicillins having the general formula (I) and salts and hydrated forms thereof, wherein T is a C 2 -C 5 alkyl or alkenyl group or a cyclopropylmethyl, cyclobutylmethyl or cyclopentyl group, and A is a furyl, tetrahydrofuryl, pyrrolyl, pyrrolidinyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, 1,2,3-thiadiazolyl, pyridyl, imidazolyl, pyrazolyl, 1-oxidopyridyl, tetrahydropyranyl, pyrimidinyl, pyrazinyl, benzofuranyl, indolyl, quinolyl or isoquinolyl group which groups may be substituted by halogen, oxo, hydroxy, amino, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 alkoxycarbonyl and/or C 1 -C 3 alkanoylamino, are prepared by reacting 6- aminopenicillanic acid, the carboxyl group of which is protected, with an acid of general Formula (II) wherein A and T are as defined above, or with an N-acylating functional derivative thereof, cleaving off the protecting group and if desired, converting the product into a salt. Protection of the carboxyl group of the 6- aminopenicillanic acid may be by conversion into a readily cleavable ester, e.g. benzyl or a silyl ester, or by salt formation with an inorganic or organic base, e.g. triethylamine. N-acylating derivatives of the acid (II) may be halides, azides, anhydrides, reactive esters or amides. Alternatively, the acid itself may be used in the presence of a condensing agent, e.g. a carbodiimide or an oxazolium salt. The reaction is preferably conducted at - 40 to +5 C. in an inert solvent such as ethyl acetate, acetonitrile, dioxan, chloroform, methylene chloride, benzene or dimethylformamide. Pharmaceutical compositions having antibiotic activity against gram-positive and -negative bacteria comprise a penicillin of Formula (I) or a salt or hydrated form thereof together with a pharmaceutical carrier. |