@article{fc5d1da61aa940e7811c3c3423cec944,
title = "Evolution of a thienopyrimidine antitubercular relying on medicinal chemistry and metabolomics insights",
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.",
keywords = "Metabolomics, Prodrug, Thienopyrimidine, Tuberculosis",
author = "Li, {Shao Gang} and Catherine Vilch{\`e}ze and Sumit Chakraborty and Xin Wang and Hiyun Kim and Monica Anisetti and Sean Ekins and Rhee, {Kyu Y.} and Jacobs, {William R.} and Freundlich, {Joel S.}",
note = "Funding Information: J.S.F. and S.E. acknowledge support from award number R44TR000942-02 {\textquoteleft}Biocomputation across distributed private datasets to enhance drug discovery{\textquoteright} from the National Institutes of Health and National Center for Advancing Translational Sciences . J.S.F. also acknowledges support from the New Jersey Health Foundation . W.R.J. acknowledges generous support from the National Institutes of Health Grant AI26170 . K.Y.R. acknowledges support from the Bill & Melinda Gates Foundation TB Drug Accelerator and Burroughs Wellcome Career Award in the Biomedical Sciences . Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd. All rights reserved.",
year = "2015",
month = may,
day = "25",
doi = "10.1016/j.tetlet.2015.02.129",
language = "English (US)",
volume = "56",
pages = "3246--3250",
journal = "Tetrahedron Letters",
issn = "0040-4039",
publisher = "Elsevier Limited",
number = "23",
}