X-ray crystal structure of 4-deoxy-3'-bromopyrido(1',2'-1,2)imidazo(5,4-c)rifamycin S.

Abstract

This paper reports the determination of the X-ray molecular structure of 4-deoxy-3''-bromopyrido[1'',2''-1,2]-imidazo[5,4-c]rifamycin S, carried out in order to unequivocally define the general structure of a new series of rifamycin SV derivatives, which are potent antibacterial agents and are not absorbed at the gastroenteric level. They were prepared by condensing 2-aminopyridine derivatives to 3-bromorifamycin S. The solid state X-ray study confirmed the structure proposed on the basis of 1H NMR studies in solution. The newly formed pyridoimidazo system is in a mesomeric betaine form, the pyrido N being positively charged and the imidazo N being negatively charged. This feature is believed responsible for the pharmacokinetic behavior of these new drugs, one of which, denoted as rifamycin L 105 or rifaximin, is actually under clinical trial as a topical intestinal disinfectant.