855405-22-0Relevant academic research and scientific papers
Generation and exploration of new classes of antitubercular agents: The optimization of oxazolines, oxazoles, thiazolines, thiazoles to imidazo[1,2-a]pyridines and isomeric 5,6-fused scaffolds
Moraski, Garrett C.,Markley, Lowell D.,Chang, Mayland,Cho, Sanghyun,Franzblau, Scott G.,Hwang, Chang Hwa,Boshoff, Helena,Miller, Marvin J.
supporting information; experimental part, p. 2214 - 2220 (2012/05/20)
Tuberculosis (TB) is a devastating disease resulting in a death every 20 s. Thus, new drugs are urgently needed. Herein we report ten classes of compounds - oxazoline, oxazole, thiazoline, thiazole, pyrazole, pyridine, isoxazole, imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine and imidazo[1,2-c]pyrimidine - which have good (micromolar) to excellent (sub-micromolar) antitubercular potency. The 5,6-fused heteroaromatic compounds were the most potent with MIC's as low as 37Rv, clinically relevant drug sensitive, multi- and extensively resistant Mtb strains as well as having good in vitro metabolic stability.
Structure-activity relationship of new anti-tuberculosis agents derived from oxazoline and oxazole benzyl esters
Moraski, Garrett C.,Chang, Mayland,Villegas-Estrada, Adriel,Franzblau, Scott G.,M?llmann, Ute,Miller, Marvin J.
experimental part, p. 1703 - 1716 (2010/06/19)
During the syntheses and studies of natural iron chelators (mycobactins), we serendipitously discovered that a simple, small molecule, oxazoline-containing intermediate 3 displayed surprising anti-tuberculosis activity (MIC of 7.7?μM, average). Herein we
N -((1-benzyl-1 H -1,2,3-triazol-4-yl)methyl)arylamide as a new scaffold that provides rapid access to antimicrotubule agents: Synthesis and evaluation of antiproliferative activity against select cancer cell lines
Stefely, Jonathan A.,Palchaudhuri, Rahul,Miller, Patricia A.,Peterson, Rebecca J.,Moraski, Garrett C.,Hergenrother, Paul J.,Miller, Marvin J.
supporting information; experimental part, p. 3389 - 3395 (2010/09/04)
A series of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamides was synthesized by copper-catalyzed azide-alkyne cycloaddition (CuAAC) and afforded inhibitors of cancer cell growth. For example, compound 13e had an IC 50 of 46 nM against MCF-7 human breast tumor cells. Structure-activity relationship (SAR) studies demonstrated that (i) meta-phenoxy substitution of the N-1-benzyl group is important for antiproliferative activity and (ii) a variety of heterocyclic substitutions for the aryl group of the arylamide are tolerated. In silico COMPARE analysis of antiproliferative activity against the NCI-60 human tumor cell line panel revealed a correlation to clinically useful antimicrotubule agents such as paclitaxel and vincristine. This in silico correlation was supported by (i) in vitro inhibition of tubulin polymerization, (ii) G2/M-phase arrest in HeLa cells as assessed by flow cytometry, and (iii) perturbation of normal microtubule activity in HeLa cells as observed by confocal microscopy. The results demonstrate that N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamide is a readily accessible small molecule scaffold for compounds that inhibit tubulin polymerization and tumor cell growth.
