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Synthesis and Structure-Activity Relationships of a New Oral Cephalosporin, BMY-28100 and Related Compounds

Synthesis and Structure-Activity Relationships of a New Oral Cephalosporin, BMY-28100 and Related Compounds

T Naito, H Hoshi, S Aburaki, Y Abe, J Okumura, K Tomatsu, H Kawaguchi

J Antibiot (Tokyo). 1987 Jul;40(7):991-1005.

PMID: 3624077

Abstract:

The synthesis and structure-activity relationships of 7-[D-alpha-amino-alpha-(4-hydroxyphenyl)-acetamido]-3-[(Z)-1-propenyl]- 3-cephem-4-carboxylic acid (BMY-28100) and its analogs in the 3- and 7-side chains are described. The 3-(substituted-propenyl) groups were introduced by the Wittig reaction of the 3-phosphoniomethyl cephems which were derived from the 3-chloromethyl derivatives. The reaction gave predominantly the cis isomer regarding the 3-side chain. The cis and trans isomers showed characteristic UV and 1H NMR spectra. Most of cephems of this series were well-absorbed orally and more active both in vitro and in vivo than cephalexin and cefaclor against Gram-positive organisms. Their Gram-negative activity varied depending on the 3- and 7-substituents. Compounds with a cis-propenyl group showed the best Gram-negative activity among the 3-alkenyl analogs prepared, whereas the D-4-hydroxyphenylglycyl and D-4-hydroxy-3-methoxyphenylglycyl substitutions in the 7-side chain were found suitable to improve the Gram-negative activity of 3-cis-propenyl series of cephalosporins to the level favorably compared with that of cefaclor. The 3,4-dihydroxyphenyl analog was found to be metabolized in vivo to the 4-hydroxy-3-methoxyphenyl derivative and, therefore, showed nearly the same in vivo activity as that of the latter. BMY-28100 was selected for further evaluation and the results will be reported in the subsequent paper.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP114876721	Cefprozil (Z)-Isomer		114876-72-1	Price
AP34876352	Cephalexin Related Compound D		34876-35-2	Price

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