| 摘要 |
1480027 Cephalosporin derivatives BRISTOLMYERS CO 20 May 1975 [24 May 1974 (2)] 21509/75 Heading C2C Novel compounds I having the D configuration in the 7-side chain (X is 3-hydroxy-pyridazin-6-yl or tetrazolo- [4,5 - b]pyridazin - 6 - yl; R=2- or 3-thienyl or phenyl optionally substituted by Cl, Br, F, CF 3 , NH 2 , NO 2 , OH, 1-4 C alkyl or 1-4 C alkoxy) and salts and easily hydrolysed esters thereof are prepared by reaction of the corresponding 7-amino derivatives with an acylating agent RCH(OH)COOH or a reactive derivative thereof in which the hydroxy group may be protected or by reaction of the corresponding 3 - acetoxymethyl derivatives with 6 - mercapto - 3 - hydroxy - pyridazine or 6 - mercapto-tetrazolo-[4,5-b]pyridazine. The 7-amino derivatives are prepared by conventional methods. Other intermediates isolated are 3-chloro-6- hydroxy - pyridazine (A), prepared by hydrolysis of the 3,6-dichloro derivative; 3-hydroxy-6- mercapto - pyridarine (B), prepared by reaction of (A) with KSH or of 3,6-dihydroxypyridazine with P 2 S 5 ; 3,6-dihydroxy-pyridazine (C), prepared by reaction of maleic anhydride with hydrazine; 3,6-dichloro-pyridazine (D), prepared by reaction of (C) with POCl 3 ; 3 - chloro - 6 - hydrazinopryidazine (E), prepared by reaction of (D) with hydrazine hydrate; 6 - chloro - tetrazolo[4,5 - b]pyridazine (F), prepared by reaction of (E) with NaNO 2 ; 6 - mercapto - tetrazolo[4,5 - b]pyridazine (G), prepared by reaction of (F) with KSH; and D - mandelic acid carboxy anhydride (H), prepared by reaction of phosgene with D(-)- mandelic acid. Pharmaceutical compositions having antibacterial activity comprise a compound I together with a suitable diluent and/or carrier. |
