3-MERCAPTOTHIAZOLE OR MERCAPTOTETRAZOLE CEPHALOSPORINS AND PROCESS FOR PREPARING THE SAME

摘要

1283811 Cephalosporins ELI LILLY & CO 17 April 1970 [18 April 1969] 18471/70 Headings C2A and C2C. Novel cephalosporins having the Formula I: and pharmaceutically acceptable salts thereof, wherein R is thienyl or optionally substituted phenyl, the substituent being Cl, Br, F, CF 3 , NH 2 , NO 2 , OH, C 1 -C 3 alkyl or C 1 -C 3 alkoxy; R 1 is of formula (III) or (IV) in which Z is H or C 1 -C 3 alkyl and Q is C 1 -C 3 alkyl; and X is -OH, -NH 2 or -NHRSP2/SP, where RSP2/SP is or are prepared either (1) by reacting an appropriate 7-acylated cephalosporanic acid with a thiol of Formula (V) or (VI): wherein Z and Q are as above, to replace the acetoxy group in the 3-position with a mercaptothiazole or mercaptotetrazole group, or (2) by acylating a 7-amino-3-mercaptothiazolyl- or a 7 - amino - 3 mercaptotetrazolyl - cephalosporanic acid with an acylating agent appropriate to introduce a group in the 7-position, XSP1/SP being or -NHRSP2/SP, and, if required, converting this group to -OH or -NH 2 . Reaction (1) may be performed in aqueous solution at 50-100‹ C. in the presence of a weak base, e.g. NaHCO 3 . Reaction (2) is effected by acylation with the appropriate amino- or hydroxy-acetic acid halide or mixed anhydride, the amino or hydroxy group being in the protected form of NHRSP2/SP or The conversion of these groups to amino and hydroxy is effected by hydrolysis. D-Mandelyl chloride formate ester is prepared by reacting D-mandelic acid with formic acid to give D-mandelic acid formate ester and treating the latter with oxalyl chloride. Pharmaceutical compositions having antibiotic activity comprise cephalosporins of Formula I above wherein X is -OH or -NH 2 or non- toxic salts thereof together with a pharmaceutically acceptable excipient.