Evolution of a thienopyrimidine antitubercular relying on medicinal chemistry and metabolomics insights. Academic Article uri icon

Overview

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.

publication date

  • June 3, 2015

Identity

PubMed Central ID

  • PMC4527344

Scopus Document Identifier

  • 84939967990

Digital Object Identifier (DOI)

  • 10.1016/j.tetlet.2015.02.129

PubMed ID

  • 26257441

Additional Document Info

volume

  • 56

issue

  • 23