GB1387251A - Antibiotics - Google Patents

Abstract

1387251 Penicillins SUMITOMO CHEMICAL CO Ltd 29 Dec 1971 [29 Dec 1970 (2)] 60428/71 Heading C2C Novel penicillins having the general Formula (I) and non-toxic salts thereof, wherein A is a substituted or unsubstituted fused aromatic carbocyclic or heterocyclic ring wherein the hetero atom is nitrogen; R is hydrogen or C 1 to C 8 alkyl; X is O or S; Y is hydrogen, C 1 to C 8 alkyl, C 1 to C 8 alkanoyl or C 1 to C 8 alkoxycarbonyl; and Z is phenyl or thienyl, are prepared by either (1) reacting 6-aminopenicillanic acid or an ester thereof, with a carboxylic acid of Formula (II) or its N-acylating reactive derivative, or (2) reacting a 6-(α-amino substituted-acetamido)- penicillanic acid of Formula (V) or an ester thereof, with a carboxylic acid of Formula (IV) or its N-acylating reactive derivative, and (3) if necessary, subsequently converting the ester group to carboxyl. The fused ring A may be a benzene ring or a 6-membered N-containing hetero aromatic ring, e.g. pyridine or pyrimidine, and may be substituted by one or more of lower alkyl, lower alkoxy, lower alkoxycarbonyl, hydroxyl, halogen, haloalkyl, nitro, lower alkylsulphonyl, mercapto, lower alkylthio, lower alkylenedioxy, lower alkylene, amino, lower alkylamino or di-(lower alkyl)amino, wherein lower means that the group has 1 to 8 carbons. Amino groups may be conventionally protected. Preferred salts are those of K, Na, Ca, Ba, Mg, substituted or unsubstituted ammonium and arginine. The preparative process is carried out in a polar, non-polar or aqueous solvent in the presence of a base. The penicillanic acid is preferably in the form of a trialkylsilyl, trichloroethyl, alkanoyloxymethyl or phenacyl ester, being de-esterified after the amidation process by reduction or hydrolysis. D - (-) - α - (4 - Hydroxyquinoline - 3 - carbonamido)-phenylacetic acid is prepared by reacting 4 - hydroxyquinoline - 3 - carboxylic acid with D-(-)-α-phenylglycine ethyl ester hydrochloride in the presence of phosgene and triethylamine and subsequently hydrolysing the ester. By an analogous procedure, D-(-)-α-(7-methyl-4- hydroxy - 1,8 - naphthyridine - 3 - carbonamido)- phenylacetic acid, and D-(-)-α-(2-methyl-6,7- methylenedioxy - 4 - hydroxyquinoline - 3- carbonamido)-phenylacetic acid are prepared using 7-methyl-4-hydroxy-1,8-naphthyridine-3- carboxylic acid, and 2-methyl-6,7-methylenedioxy-4-hydroxyquinoline-3-carboxylic acid respectively, in place of the 4-hydroxyquinoline- 3-carboxylic acid. Pharmaceutical compositions having antibacterial activity against gram-positive and -negative bacteria and especially against Pseudomonas sp. comprise a penicillin of Formula (I) as defined above, or a non-toxic salt thereof together with a pharmaceutical carrier.