BM635 is the hit compound of a promising anti-TB compound class. Herein we report systematic variationsaround the central pyrrole core of BM635 and we describe the design, synthesis, biologicalevaluation, pharmacokinetic analysis, as well as in vivo TB mouse efficacy studies of novel BM635 analoguesthat show improved physicochemical properties. This hit-to-lead campaign led to the identificationof a new analogue, 4-((1-isopropyl-5-(4-isopropylphenyl)-2-methyl-1H-pyrrol-3-yl)methyl)morpholine (17), that shows excellent activity (MIC ¼ 0.15 mM; SI ¼ 133) against drug-sensitive Mycobacteriumtuberculosis strains, as well as efficacy in a murine model of TB infection
In vivo potent BM635 analogue with improved drug-like properties
Consalvi, Sara;
2018-01-01
Abstract
BM635 is the hit compound of a promising anti-TB compound class. Herein we report systematic variationsaround the central pyrrole core of BM635 and we describe the design, synthesis, biologicalevaluation, pharmacokinetic analysis, as well as in vivo TB mouse efficacy studies of novel BM635 analoguesthat show improved physicochemical properties. This hit-to-lead campaign led to the identificationof a new analogue, 4-((1-isopropyl-5-(4-isopropylphenyl)-2-methyl-1H-pyrrol-3-yl)methyl)morpholine (17), that shows excellent activity (MIC ¼ 0.15 mM; SI ¼ 133) against drug-sensitive Mycobacteriumtuberculosis strains, as well as efficacy in a murine model of TB infectionI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
