RT Journal Article
SR Electronic
T1 A study of structure-activity relationships in 4-deoxypyrido[1',2'-1,2]imidazo[5,4-c]rifamycin SV derivatives by electron spectroscopy for chemical analysis and 1H NMR.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 103
OP 108
VO 27
IS 1
A1 L Cellai
A1 S Cerrini
A1 A Segre
A1 C Battistoni
A1 G Cossu
A1 G Mattogno
A1 M Brufani
A1 E Marchi
YR 1985
UL http://molpharm.aspetjournals.org/content/27/1/103.abstract
AB A new class of rifamycins, 4-deoxypyrido[1',2'-1,2]imidazo[5,4-c]rifamycin SV derivatives, has been synthesized. They are potent antibacterial agents and are not absorbed at the gastrointestinal level and can therefore probably be used as antibacterial intestinal disinfectants. From the present X-ray, electron spectroscopy for chemical analysis, and 1H NMR study, it appears that this peculiar pharmacokinetic behavior is mainly to be attributed to the fact that the pyridoimidazo system exists in these compounds in a mesomeric betaine form, bearing one positively and one negatively charged nitrogen. If it is assumed that rifamycins are generally absorbed by passive diffusion, the presence of the two oppositely charged nitrogens, together with the presence of the phenolic hydroxyls, means that these molecules are ionized at all pH values encountered along the gastrointestinal tract, which thus prevents their absorption. These molecules also display a strong tendency to self-associate both in solution and in the solid state, and the increase in molecular size may also play a role in preventing their absorption.