177943-33-8

Basic information

• Product Name: (S)-3-aMino-1-hydroxy-3,4-dihydroquinolin-2(1H)-one hydrochloride
• Synonyms: (S)-3-aMino-1-hydroxy-3,4-dihydroquinolin-2(1H)-one hydrochloride;(3S)-3-Amino-1-hydroxy-3,4-dihydroquinolin-2(1H)-one;L-3-Amino-3,4-dihydro-1-hydroxycarbstyril hydrochloride;PF04859989 hydrochloride;PF-04859989 hydrochloride;PF-4859989 hydrochloride;PF-04859989
• CAS NO: 177943-33-8
• Molecular Formula: C₉H₁₀N₂O₂*ClH
• Molecular Weight: 214.64884
• Mol File: 177943-33-8.mol
• Article Data: 1

Chemical Properties

• Appearance: white to beige/
• Storage Temp.: room temp
• Solubility: H2O: soluble20mg/mL, clear
• CAS DataBase Reference: (S)-3-aMino-1-hydroxy-3,4-dihydroquinolin-2(1H)-one hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-3-aMino-1-hydroxy-3,4-dihydroquinolin-2(1H)-one hydrochloride(177943-33-8)
• EPA Substance Registry System: (S)-3-aMino-1-hydroxy-3,4-dihydroquinolin-2(1H)-one hydrochloride(177943-33-8)

Safety Data

• Hazardous Substances Data: 177943-33-8(Hazardous Substances Data)

Usage

Biochem/physiol Actions

PF-04859989 is a brain-penetrable irreversible inhibitor of kynurenine amino transferase II (KAT II), the enzyme responsible for most of the brain synthesis of kynurenic acid, which has been implicated in several psychiatric and neurological disorders, including schizophrenia and bipolar disorder, and thought to impair cognitive function. PF-04859989 has IC50 values of 23 nM for hKAT II and 263 nM for rKAT II. PF-04859989 is ~1000-fold selective for KAT II over human KAT I, KAT III, and KAT IV. PF-04859989 prevented ketamine-induced disruption of performance in memory tasks in both rodents and nonhuman primates.

Upstream product

• 1991-82-8 (2S)-2-amino-3-(2-nitrophenyl)propanoic acid 

Relevant articles and documents

Discovery of brain-penetrant, irreversible kynurenine aminotransferase ii inhibitors for schizophrenia

Kynurenine aminotransferase (KAT) II has been identified as a potential new target for the treatment of cognitive impairment associated with schizophrenia and other psychiatric disorders. Following a high-throughput screen, cyclic hydroxamic acid PF-04859989 was identified as a potent and selective inhibitor of human and rat KAT II. An X-ray crystal structure and 13C NMR studies of PF-04859989 bound to KAT II have demonstrated that this compound forms a covalent adduct with the enzyme cofactor, pyridoxal phosphate (PLP), in the active site. In vivo pharmacokinetic and efficacy studies in rat show that PF-04859989 is a brain-penetrant, irreversible inhibitor and is capable of reducing brain kynurenic acid by 50% at a dose of 10 mg/kg (sc). Preliminary structurea€"activity relationship investigations have been completed and have identified the positions on this scaffold best suited to modification for further optimization of this novel series of KAT II inhibitors.