Structure-activity relationships of compounds targeting mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase

Jialin Mao; Hyungjin Eoh; Rong He; Yuehong Wang; Baojie Wan; Scott G. Franzblau; Dean C. Crick; Alan P. Kozikowski

doi:10.1016/j.bmcl.2008.08.034

Structure-activity relationships of compounds targeting mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase

Jialin Mao, Hyungjin Eoh, Rong He, Yuehong Wang, Baojie Wan, Scott G. Franzblau, Dean C. Crick, Alan P. Kozikowski

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

We report on a target-based approach to identify possible Mycobacterium tuberculosis DXS inhibitors from the structure of a known transketolase inhibitor. A small focused library of analogs was assembled in order to begin elucidating some meaningful structure-activity relationships of 3-(4-chloro-phenyl)-5-benzyl-4H-pyrazolo[1,5-a]pyrimidin-7-one. Ultimately we found that 2-methyl-3- (4-fluorophenyl)-5-(4-methoxy-phenyl)-4H-pyrazolo[1,5-a]pyrimidin-7-one, although still weak, was able to inhibit M. tuberculosis DXS with an IC₅₀ of 10.6 μM.

Original language	English (US)
Pages (from-to)	5320-5323
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	19
DOIs	https://doi.org/10.1016/j.bmcl.2008.08.034
State	Published - Oct 1 2008
Externally published	Yes

Keywords

DXS
Drug design
Enzyme
SAR
Tuberculosis

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2008.08.034

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title = "Structure-activity relationships of compounds targeting mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase",

abstract = "We report on a target-based approach to identify possible Mycobacterium tuberculosis DXS inhibitors from the structure of a known transketolase inhibitor. A small focused library of analogs was assembled in order to begin elucidating some meaningful structure-activity relationships of 3-(4-chloro-phenyl)-5-benzyl-4H-pyrazolo[1,5-a]pyrimidin-7-one. Ultimately we found that 2-methyl-3- (4-fluorophenyl)-5-(4-methoxy-phenyl)-4H-pyrazolo[1,5-a]pyrimidin-7-one, although still weak, was able to inhibit M. tuberculosis DXS with an IC50 of 10.6 μM.",

keywords = "DXS, Drug design, Enzyme, SAR, Tuberculosis",

author = "Jialin Mao and Hyungjin Eoh and Rong He and Yuehong Wang and Baojie Wan and Franzblau, {Scott G.} and Crick, {Dean C.} and Kozikowski, {Alan P.}",

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AU - Mao, Jialin

AU - Eoh, Hyungjin

AU - He, Rong

AU - Wang, Yuehong

AU - Wan, Baojie

AU - Franzblau, Scott G.

AU - Crick, Dean C.

AU - Kozikowski, Alan P.

PY - 2008/10/1

Y1 - 2008/10/1

N2 - We report on a target-based approach to identify possible Mycobacterium tuberculosis DXS inhibitors from the structure of a known transketolase inhibitor. A small focused library of analogs was assembled in order to begin elucidating some meaningful structure-activity relationships of 3-(4-chloro-phenyl)-5-benzyl-4H-pyrazolo[1,5-a]pyrimidin-7-one. Ultimately we found that 2-methyl-3- (4-fluorophenyl)-5-(4-methoxy-phenyl)-4H-pyrazolo[1,5-a]pyrimidin-7-one, although still weak, was able to inhibit M. tuberculosis DXS with an IC50 of 10.6 μM.

AB - We report on a target-based approach to identify possible Mycobacterium tuberculosis DXS inhibitors from the structure of a known transketolase inhibitor. A small focused library of analogs was assembled in order to begin elucidating some meaningful structure-activity relationships of 3-(4-chloro-phenyl)-5-benzyl-4H-pyrazolo[1,5-a]pyrimidin-7-one. Ultimately we found that 2-methyl-3- (4-fluorophenyl)-5-(4-methoxy-phenyl)-4H-pyrazolo[1,5-a]pyrimidin-7-one, although still weak, was able to inhibit M. tuberculosis DXS with an IC50 of 10.6 μM.

KW - DXS

KW - Drug design

KW - Enzyme

KW - SAR

KW - Tuberculosis

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ER -

Structure-activity relationships of compounds targeting mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase

Abstract

Keywords

ASJC Scopus subject areas

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