Submitted by san2025 on January 12, 2022 - 9:33pm
Title | Evolution of a thienopyrimidine antitubercular relying on medicinal chemistry and metabolomics insights. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Li S-G, Vilchèze C, Chakraborty S, Wang X, Kim H, Anisetti M, Ekins S, Rhee KY, Jacobs WR, Freundlich JS |
Journal | Tetrahedron Lett |
Volume | 56 |
Issue | 23 |
Pagination | 3246-3250 |
Date Published | 2015 Jun 03 |
ISSN | 0040-4039 |
Abstract | The metabolic instability of an antitubercular small molecule CD117 was addressed through iterative alteration of a key sulfide substituent and interrogation of the effect on growth inhibition of cultured Mycobacterium tuberculosis. This process was informed by studies of the intramycobacterial metabolism of CD117 and its inactive carboxylic acid derivative. Isoxazole 4e and thiazole 4m demonstrated significant gains in mouse liver microsomal stability with slight losses in whole-cell activity. This work illustrates the challenges of antitubercular hit evolution, requiring a balance of chemical and biological insights. |
DOI | 10.1016/j.tetlet.2015.02.129 |
Alternate Journal | Tetrahedron Lett |
PubMed ID | 26257441 |
PubMed Central ID | PMC4527344 |
Grant List | R01 AI026170 / AI / NIAID NIH HHS / United States R37 AI026170 / AI / NIAID NIH HHS / United States R44 TR000942 / TR / NCATS NIH HHS / United States |