Novel Pyrimidines as Antitubercular Agents.

Autor:	Inoyama D; Department of Pharmacology, Physiology and Neuroscience, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.; Ruy V. Lourenço Center for the Study of Emerging and Re-Emerging Pathogens, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA., Paget SD; Department of Pharmacology, Physiology and Neuroscience, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.; Ruy V. Lourenço Center for the Study of Emerging and Re-Emerging Pathogens, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA., Russo R; Division of Infectious Disease, Department of Medicine, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.; Ruy V. Lourenço Center for the Study of Emerging and Re-Emerging Pathogens, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA., Kandasamy S; Department of Pharmacology, Physiology and Neuroscience, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.; Ruy V. Lourenço Center for the Study of Emerging and Re-Emerging Pathogens, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA., Kumar P; Division of Infectious Disease, Department of Medicine, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.; Ruy V. Lourenço Center for the Study of Emerging and Re-Emerging Pathogens, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA., Singleton E; Division of Infectious Disease, Department of Medicine, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.; Ruy V. Lourenço Center for the Study of Emerging and Re-Emerging Pathogens, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA., Occi J; Division of Infectious Disease, Department of Medicine, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.; Ruy V. Lourenço Center for the Study of Emerging and Re-Emerging Pathogens, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA., Tuckman M; Division of Infectious Disease, Department of Medicine, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.; Ruy V. Lourenço Center for the Study of Emerging and Re-Emerging Pathogens, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA., Zimmerman MD; Public Health Research Institute, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA., Ho HP; Public Health Research Institute, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA., Perryman AL; Department of Pharmacology, Physiology and Neuroscience, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.; Ruy V. Lourenço Center for the Study of Emerging and Re-Emerging Pathogens, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA., Dartois V; Public Health Research Institute, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA., Connell N; Division of Infectious Disease, Department of Medicine, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.; Ruy V. Lourenço Center for the Study of Emerging and Re-Emerging Pathogens, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA., Freundlich JS; Department of Pharmacology, Physiology and Neuroscience, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA freundjs@rutgers.edu.; Division of Infectious Disease, Department of Medicine, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.; Ruy V. Lourenço Center for the Study of Emerging and Re-Emerging Pathogens, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2018 Feb 23; Vol. 62 (3). Date of Electronic Publication: 2018 Feb 23 (Print Publication: 2018).
DOI:	10.1128/AAC.02063-17
Abstrakt:	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. (Copyright © 2018 American Society for Microbiology.)
Databáze:	MEDLINE
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