| Literature DB >> 29311070 |
Daigo Inoyama1,2, Steven D Paget1,2, Riccardo Russo3,2, Srinivasan Kandasamy1,2, Pradeep Kumar3,2, Eric Singleton3,2, James Occi3,2, Margareta Tuckman3,2, Matthew D Zimmerman4, Hsin Pin Ho4, Alexander L Perryman1,2, Véronique Dartois4, Nancy Connell3,2, Joel S Freundlich5,3,2.
Abstract
Mycobacterium tuberculosis infection is responsible for a global pandemic. New drugs are needed that do not show cross-resistance with the existing front-line therapeutics. A triazine antitubercular hit led to the design of a related pyrimidine family. The synthesis of a focused series of these analogs facilitated exploration of their in vitro activity, in vitro cytotoxicity, and physiochemical and absorption-distribution-metabolism-excretion properties. Select pyrimidines were then evaluated for their pharmacokinetic profiles in mice. The findings suggest a rationale for the further evolution of this promising series of antitubercular small molecules, which appear to share some similarities with the clinical compound PA-824 in terms of activation, while highlighting more general guidelines for the optimization of small-molecule antitubercular agents.Entities:
Keywords: Mycobacterium tuberculosis; antitubercular; pharmacokinetics; pyrimidine
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Year: 2018 PMID： 29311070 PMCID： PMC5826157 DOI： 10.1128/AAC.02063-17
Source DB: PubMed Journal: Antimicrob Agents Chemother ISSN： 0066-4804 Impact factor: 5.191