Novel Pyrimidines as Antitubercular Agents.

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.

authors

Inoyama D,Paget SD,Russo R,Kandasamy S,Kumar P,Singleton E,Occi J,Tuckman M,Zimmerman MD,Ho HP,Perryman AL,Dartois V,Connell N,Freundlich JS

doi

10.1128/AAC.02063-17

subject

Has Abstract

pub_date

2018-02-23 00:00:00

issue

3

eissn

0066-4804

issn

1098-6596

pii

AAC.02063-17

journal_volume

62

pub_type

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