Design and synthesis of 3-fluoro-2-oxo-3-phenylpropionic acid derivatives as potent inhibitors of 4-hydroxyphenylpyruvate dioxygenase from pig liver.
Several rationally designed analogs of 3-fluoro-2-oxo-3-phenylpropionic acid were chemically synthesized, and the reactions of the hydrate form of these compounds with 4-hydroxyphenylpyruvate dioxygenase from pig liver as inhibitors were examined. Compounds 14a and 14b were found to be potent competitive inhibitors of the enzyme with Ki values of 10 and 22 microM, respectively.
Ling
T S
TS
Department of Chemistry, Tunghai Christian University, Taichung, Taiwan, People's Republic of China.
Shiu
S
S
Yang
D Y
DY
D015111:4-Hydroxyphenylpyruvate Dioxygenase / Q000037:antagonists & inhibitors*; D000818:Animals; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000494:pharmacology; D010667:Phenylpyruvic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine
C121622:3-fluoro-3-(4-nitrophenyl)pyruvic acid; C121621:3-fluoro-3-phenylpyruvic acid; D004791:Enzyme Inhibitors; D010666:Phenylpropionates; D010667:Phenylpyruvic Acids; D015111:4-Hydroxyphenylpyruvate Dioxygenase