| http://purl.uniprot.org/citations/23566269 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23566269 | http://www.w3.org/2000/01/rdf-schema#comment | "D-Amino acid oxidase (DAAO) catalyzes the oxidation of d-amino acids including d-serine, a coagonist of the N-methyl-d-aspartate receptor. We identified a series of 4-hydroxypyridazin-3(2H)-one derivatives as novel DAAO inhibitors with high potency and substantial cell permeability using fragment-based drug design. Comparisons of complex structures deposited in the Protein Data Bank as well as those determined with in-house fragment hits revealed that a hydrophobic subpocket was formed perpendicular to the flavin ring by flipping Tyr224 in a ligand-dependent manner. We investigated the ability of the initial fragment hit, 3-hydroxy-pyridine-2(1H)-one, to fill this subpocket with the aid of complex structure information. 3-Hydroxy-5-(2-phenylethyl)pyridine-2(1H)-one exhibited the predicted binding mode and demonstrated high inhibitory activity for human DAAO in enzyme- and cell-based assays. We further designed and synthesized 4-hydroxypyridazin-3(2H)-one derivatives, which are equivalent to the 3-hydroxy-pyridine-2(1H)-one series but lack cell toxicity. 6-[2-(3,5-Difluorophenyl)ethyl]-4-hydroxypyridazin-3(2H)-one was found to be effective against MK-801-induced cognitive deficit in the Y-maze."xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.org/dc/terms/identifier | "doi:10.1021/jm400095b"xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/author | "Harada K."xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/author | "Matsumoto Y."xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/author | "Takeuchi M."xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/author | "Yamaguchi T."xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/author | "Sakashita H."xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/author | "Nakanishi K."xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/author | "Warizaya M."xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/author | "Namatame I."xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/author | "Niimi T."xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/author | "Orita M."xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/author | "Hamajima T."xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/author | "Hondo T."xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/name | "J Med Chem"xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/pages | "3582-3592"xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/title | "4-Hydroxypyridazin-3(2H)-one derivatives as novel D-amino acid oxidase inhibitors."xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://purl.uniprot.org/core/volume | "56"xsd:string |
| http://purl.uniprot.org/citations/23566269 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23566269 |
| http://purl.uniprot.org/citations/23566269 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23566269 |
| http://purl.uniprot.org/uniprot/#_P14920-mappedCitation-23566269 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23566269 |
| http://purl.uniprot.org/uniprot/P14920 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/23566269 |