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 IC(50) of 10.6 microM.
authors.affiliation: Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA.
authors.forename: Jialin
authors.initials: J
authors.lastname: Mao
authors.forename: Hyungjin
authors.initials: H
authors.lastname: Eoh
authors.forename: Rong
authors.initials: R
authors.lastname: He
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Wang
authors.forename: Baojie
authors.initials: B
authors.lastname: Wan
authors.forename: Scott G
authors.initials: SG
authors.lastname: Franzblau
authors.forename: Dean C
authors.initials: DC
authors.lastname: Crick
authors.forename: Alan P
authors.initials: AP
authors.lastname: Kozikowski
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014166:Transferases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: C532525:2-methyl-3-(4-fluorophenyl)-5-(4-methoxy-phenyl)-4H-pyrazolo(1,5-a)pyrimidin-7-one; D000995:Antitubercular Agents; D011720:Pyrazoles; D011743:Pyrimidines; D014166:Transferases; C109461:deoxyxylulose-5-phosphate synthase
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