134479-98-4Relevant academic research and scientific papers
Synthesis and total 1H- and 13C-NMR assignment of cephem derivatives for use in ADEPT approaches
Blau, Lorena,Menegon, Renato Farina,Ferreira, Elizabeth Igne,Ferreira, Antonio Gilberto,Boffo, Elisangela Fabiana,Tavares, Leila Aley,Heleno, Vladimir Constantino Gomes,Chung, Man-Chin
, p. 841 - 854 (2008/09/18)
We report the synthesis and total NMR characterization of 5-thia-1-azabicyclo-[4.2.0]oct-2-ene-2-carboxylic acid-3-[[[(4″- nitrophenoxy)carbonyl]oxy]-methyl]-8-oxo-7-[(2-thienyloxoacetyl)amino] -diphenylmethyl ester-5-dioxide (5), a new cephalosporin derivative. This compound can be used as the carrier of a wide range of drugs containing an amino group. The preparation of the intermediate product, 5-thia-1-azabicyclo[4.2.0] oct-2-ene-2-carboxylic acid-3-[methyl 4-(6-methoxyquinolin-8-ylamino) pentylcarbamate]-8-oxo-7-[(2-thienyloxoacetyl)amino]-diphenylmethyl ester-5-dioxide (6), as well as the synthesis of the antimalarial primaquine prodrug 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid-3-[methyl 4-(6-methoxyquinolin-8-ylamino)pentylcarbamate]-8-oxo-7-[(2-thienyloxoacetyl) amino]- 5-dioxide (7) are also described, together with their total 1H- and 13C-NMR assignments.
Synthesis of Acylhydrazido-Substituted Cephems. Design of Cephalosporin-Vinca Alkaloid Prodrugs: Substrates for an Antibody-Targeted Enzyme
Jungheim, Louis N.,Shepherd, Timothy A.,Meyer, Damon L.
, p. 2334 - 2340 (2007/10/02)
Cephalosporin 20 substituted at the C-3' position with the potent oncolytic agent desacetylvinblastine hydrazide (3) was synthesized as a potential prodrug for the treatment of solid tumors.The design of this novel prodrug was based on the knowledge that hydrolysis of a cephalosporin's β-lactam bond can result in the expulsion of the C-3' substituent.Proper selection of the linkage used to join the cephem to the vinca, e.g. 8 vs 20, provided a releasable form of the drug as well as a chemically stable prodrug.We envisioned the conversion of prodrug to free vinca to be mediated by an immunoconjugate, consisting of a β-lactamase enzyme covalently attached to a monoclonal antibody, which has been prelocalized at the tumor.Treatment of candidate prodrugs with the P99 β-lactamase enzyme isolated from Enterobacter cloacae 265A efficiently catalyzed their conversion to the free drug form.A study of model compounds 11 and 18 indicated that cephem 1-β-sulfoxide 18 was a better substrate for the enzyme than its sulfide counterpart 11.This finding prompted the synthesis of cephem sulfoxide 20 which was efficiently accomplished via condensation of desacetylvinblastine hydrazide with the cephalothin derived cephem 3'-p-nitrophenyl carbonate 15.
