Discovery of imidazole glycerol phosphate dehydratase inhibitors through 3-D database searching.
Imidazole glycerol phosphate dehydratase (IGPD) has become an attractive target for herbicide discovery since it is present in plants and not in mammals. Currently no knowledge is available on the 3-D structure of the IGPD active site. Therefore, we used a pharmacophore model based on known inhibitors and 3-D database searches to identify new active compounds. In vitro testing of compounds from the database searches led to the identification of a class of pyrrole aldehydes as novel inhibitors of IGPD.
Schweitzer
Barbara A
BA
Monsanto Company, 800 N. Lindbergh Blvd., St. Louis, MO 63167, USA. barbara.a.schweitzer@pharmacia.com
Loida
Paul J
PJ
CaJacob
Claire A
CA
Chott
Robert C
RC
Collantes
Elizabeth M
EM
Hegde
Shridhar G
SG
Mosier
Philip D
PD
Profeta
Salvatore
S
D000447:Aldehydes / Q000032:analysis / Q000737:chemistry; D001665:Binding Sites; D016208:Databases, Factual; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006540:Herbicides / Q000737:chemistry; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008968:Molecular Conformation; D011758:Pyrroles / Q000032:analysis / Q000737:chemistry*; D014230:Triazoles / Q000737:chemistry*
D000447:Aldehydes; D004791:Enzyme Inhibitors; D006540:Herbicides; D011758:Pyrroles; D014230:Triazoles; D006836:Hydro-Lyases; C021434:imidazoleglycerolphosphate dehydratase