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 journalArticle

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 languageEnglish (US)
Pages (from-to)5320-5323
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number19
DOIs
StatePublished - Oct 1 2008
Externally publishedYes

Fingerprint

Transketolase
Structure-Activity Relationship
Mycobacterium tuberculosis
Inhibitory Concentration 50
Libraries
xylulose-5-phosphate
2-methyl-3-(4-fluorophenyl)-5-(4-methoxy-phenyl)-4H-pyrazolo(1,5-a)pyrimidin-7-one

Keywords

  • Drug design
  • DXS
  • Enzyme
  • SAR
  • Tuberculosis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Structure-activity relationships of compounds targeting mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase. / Mao, Jialin; Eoh, Hyungjin; He, Rong; Wang, Yuehong; Wan, Baojie; Franzblau, Scott G.; Crick, Dean C.; Kozikowski, Alan P.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 18, No. 19, 01.10.2008, p. 5320-5323.

Research output: Contribution to journalArticle

Mao, Jialin ; Eoh, Hyungjin ; He, Rong ; Wang, Yuehong ; Wan, Baojie ; Franzblau, Scott G. ; Crick, Dean C. ; Kozikowski, Alan P. / Structure-activity relationships of compounds targeting mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase. In: Bioorganic and Medicinal Chemistry Letters. 2008 ; Vol. 18, No. 19. pp. 5320-5323.
@article{7ec2fc0c975b412d9d11c7b583b8d810,
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 = "Drug design, DXS, 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.}",
year = "2008",
month = "10",
day = "1",
doi = "10.1016/j.bmcl.2008.08.034",
language = "English (US)",
volume = "18",
pages = "5320--5323",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "19",

}

TY - JOUR

T1 - Structure-activity relationships of compounds targeting mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase

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 - Drug design

KW - DXS

KW - Enzyme

KW - SAR

KW - Tuberculosis

UR - http://www.scopus.com/inward/record.url?scp=52049084364&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=52049084364&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2008.08.034

DO - 10.1016/j.bmcl.2008.08.034

M3 - Article

VL - 18

SP - 5320

EP - 5323

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 19

ER -