title: Design and synthesis of novel inhibitors of human kynurenine aminotransferase-I.
abstract: Herein we report 6-ethoxy-6-oxo-5-(2-phenylhydrazono) hexanoic acid and 3-(2-carboxyethyl)-1H-indole-2-carboxylic acid derivatives as synthetically accessible leads for human kynurenine aminotransferase-I (KAT-I) inhibitors. In total, 12 compounds were synthesized and their biological activities were determined using the HPLC-UV based KAT-I inhibition assay. Of the 12 compounds synthesized, 10 were found to inhibit human KAT-I and the most active compound was found to be 5-(2-(4-chlorophenyl) hydrazono)-6-ethoxy-6-oxohexanoic acid (9a) with an IC(50) of 19.8 μM.
authors.affiliation: Faculty of Pharmacy A15, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Fady N
authors.initials: FN
authors.lastname: Akladios
authors.forename: Naveed A
authors.initials: NA
authors.lastname: Nadvi
authors.forename: Joohong
authors.initials: J
authors.lastname: Park
authors.forename: Jane R
authors.initials: JR
authors.lastname: Hanrahan
authors.forename: Vimal
authors.initials: V
authors.lastname: Kapoor
authors.forename: Mark D
authors.initials: MD
authors.lastname: Gorrell
authors.forename: W Bret
authors.initials: WB
authors.lastname: Church
mesh_terms: D002208:Caproates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D012559:Schizophrenia / Q000188:drug therapy; D000637:Transaminases / Q000037:antagonists & inhibitors*
chemical_list: C572257:5-(2-(4-chlorophenyl)hydrazono)-6-ethoxy-6-oxohexanoic acid; D002208:Caproates; D004791:Enzyme Inhibitors; D006834:Hydrazines; D000637:Transaminases; C021481:kynurenine-oxoglutarate transaminase