Chiral DNA gyrase inhibitors. 2. Asymmetric synthesis and biological activity of the enantiomers of 9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H- pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid (ofloxacin)

L A Mitscher; P N Sharma; D T Chu; L L Shen; A G Pernet

doi:10.1021/jm00395a017

Chiral DNA gyrase inhibitors. 2. Asymmetric synthesis and biological activity of the enantiomers of 9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H- pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid (ofloxacin)

J Med Chem. 1987 Dec;30(12):2283-6. doi: 10.1021/jm00395a017.

Authors

L A Mitscher¹, P N Sharma, D T Chu, L L Shen, A G Pernet

Affiliation

¹ Department of Medicinal Chemistry, Kansas University, Lawrence 66045.

PMID: 2824776
DOI: 10.1021/jm00395a017

Abstract

A short and efficient synthesis, starting with (R)- and (S)-alaninol, of the two optical antipodes of the quinolone antimicrobial agent ofloxacin has been devised. Testing in vitro of the products against a range of bacteria and in an assay system incorporating purified DNA gyrase from different bacterial species demonstrates that the S-(-) enantiomer is substantially the more active.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / pharmacology
Ofloxacin
Oxazines / chemical synthesis*
Oxazines / pharmacology
Stereoisomerism
Topoisomerase II Inhibitors*

Substances

Anti-Bacterial Agents
Oxazines
Topoisomerase II Inhibitors
Ofloxacin