150215-30-8Relevant articles and documents
7-acylamino-3-heteroarylthio-3-cephem carboxylic acid antibiotics and prodrugs thereof
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, (2008/06/13)
The present invention relates to a cephem prodrug having formula III or formula IV: or a pharmaceutically acceptable salt thereof, wherein R′1is selected from the group consisting of hydrogen and —C(O)CH(NH2)CH3and R′2is selected from the group consisting of hydrogen and an acyl group that is cleaved by an enzyme found in mammals, with the proviso that, when either R′1or R′2is hydrogen, the other is not. A, B, L, G, E, and J are each independently nitrogen or carbon such that the respective rings are selected from the group consisting of provided that the group —CH2—S—CH2CH2NHR′2is attached only to a carbon atom of said heterocyclic group, and Q is selected from the group consisting of nitrogen and —CX, wherein X is selected from the group consisting of hydrogen and chlorine.
Practical preparation of (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetic acid: A side-chain of the fourth generation of cephem antibiotics
Tatsuta,Miura,Gunji,Tamai,Yoshida,Inagaki,Kurita
, p. 1701 - 1707 (2007/10/02)
A Z-isomer (4) of 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)acetic acid, which is the common acyl moiety of clinically useful cephem antibiotics, has been prepared from the aminoisoxazoles through the skeletal rearrangement in several routes. Reaction of 3-amino-5-methoxyisoxazole (7) with alkoxycarbonyl isothiocyanates gave methyl 2-(5-alkoxycarbonylamino-1,2,4-thiadiazol-3-yl)acetates (8), which were converted into the target compound 4 through the reaction of the corresponding keto ester with O-methylhydroxylamime. Compound 4 was prepared similarly from 3-aminoisoxazole (10). Also, O-methylation of 2-hydroxyimino-2-(5-methoxycarbonylamino-1,2,4-thiazol-3-yl)acetate (15) with methyl iodide or dimethyl sulfate in the presence of barium oxide and barium hydroxide octahydrate was found to afford exclusively the desired Z-isomer (14a) of methyl 2-(5-methoxycarbonylamino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)aceta te, which was led to 4.