title: SAR studies of 3-cyclopropanecarbonyloxy-2-cyclohexen-1-one as inhibitors of 4-hydroxyphenylpyruvate dioxygenase.
abstract: Various 3-cyclopropanecarbonyloxy-2-cyclohexen-1-one 1 derivatives have been synthesized and tested as inhibitors of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) from pig liver. The inhibition results indicated that well-positioned dicarbonyl groups as well as the cyclopropyl group of 1 were essential for potent inhibition. Substitution at the 2-position of the ring system has a significant effect on inhibitor potency, while the 5-position can undergo substantial variations and retain inhibitor potency. In the compounds examined, 2-chloro substituted 12 is the best inhibitor of all with IC(50) of 15 nM, the rest of the synthesized analogues were less potent inhibitors than the parent compound.
authors.affiliation: Department of Chemistry, Tunghai University, 181, Taichung-Kang Rd. Sec. 3, Taichung, Taiwan 40704, ROC.
authors.forename: Yung-Lung
authors.initials: YL
authors.lastname: Lin
authors.forename: Chung-Shieh
authors.initials: CS
authors.lastname: Wu
authors.forename: Shean-Woei
authors.initials: SW
authors.lastname: Lin
authors.forename: Jian-Lin
authors.initials: JL
authors.lastname: Huang
authors.forename: Yang-Sheng
authors.initials: YS
authors.lastname: Sun
authors.forename: Ding-Yah
authors.initials: DY
authors.lastname: Yang
mesh_terms: D015111:4-Hydroxyphenylpyruvate Dioxygenase / Q000037:antagonists & inhibitors*; D000818:Animals; D003510:Cyclohexanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003512:Cyclohexanones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D053138:Cyclohexenes; D003521:Cyclopropanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008099:Liver / Q000201:enzymology; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: C473418:3-cyclopropanecarbonyloxy-2-cyclohexen-1-one; D003510:Cyclohexanes; D003512:Cyclohexanones; D053138:Cyclohexenes; D003521:Cyclopropanes; D004791:Enzyme Inhibitors; C052568:cyclohexene; C030797:cyclopropane; D015111:4-Hydroxyphenylpyruvate Dioxygenase