Elaboration of a proprietary thymidylate kinase inhibitor motif towards anti-tuberculosis agents.

Authors :: Song L
Risseeuw MDP
Froeyen M
Karalic I
Goeman J
Cappoen D
Van der Eycken J
Cos P
Munier-Lehmann H
Van Calenbergh S
Source :: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2016 Nov 01; Vol. 24 (21), pp. 5172-5182. Date of Electronic Publication: 2016 Aug 24.
Publication Year :: 2016
Abstract: We report the design and synthesis of a series of non-nucleoside MtbTMPK inhibitors (1-14) based on the gram-positive bacterial TMPK inhibitor hit compound 1. A practical synthesis was developed to access these analogues. Several compounds show promising MtbTMPK inhibitory potency and allow the establishment of a structure-activity relationship, which is helpful for further optimization.<br /> (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Subjects :: Antitubercular Agents chemical synthesis
Antitubercular Agents chemistry
Dose-Response Relationship, Drug
Humans
Microbial Sensitivity Tests
Models, Molecular
Molecular Structure
Mycobacterium tuberculosis enzymology
Nucleoside-Phosphate Kinase metabolism
Piperidines chemical synthesis
Piperidines chemistry
Protein Kinase Inhibitors chemical synthesis
Protein Kinase Inhibitors chemistry
Structure-Activity Relationship
Antitubercular Agents pharmacology
Mycobacterium tuberculosis drug effects
Nucleoside-Phosphate Kinase antagonists & inhibitors
Piperidines pharmacology
Protein Kinase Inhibitors pharmacology

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