PF-04859989 HCl

• CAT Number: I008666
• CAS Number: 177943-33-8
• Molecular Formula: C7H6BrCl2NO2
• Molecular Weight: 286.93
• Purity: 98%
• Synonyms: PF-04859989 HCl; PF-04859989HCl; PF-04859989; PF 04859989; PF04859989.;2-(Bromomethyl)-1-chloro-3-nitrobenzene HCl
• Target: KAT II Inhibitor
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Storage: 0 - 4 °C for short term, or -20 °C for long term
• Related CAS: 56433-01-3 (PF-04859989);
• Analysis method: HPLC
• IUPAC Name: (3S)-3-amino-1-hydroxy-3,4-dihydroquinolin-2-one;hydrochloride
• InChI: InChI=1S/C7H5BrClNO2.ClH/c8-4-5-6(9)2-1-3-7(5)10(11)12;/h1-3H,4H2;1H
• InChIKey: MVBWOEUQKOAQOW-UHFFFAOYSA-N
• SMILES: O=[N+](C1=C(CBr)C(Cl)=CC=C1)[O-].[H]Cl

PF-04859989 HCl(CAT: I008666) is a brain-penetrable irreversible inhibitor of kynurenine aminotransferase II (KAT II), the enzyme responsible for most of the brain synthesis of kynurenic acid. By inhibiting KAT II, PF-04859989 HCl modulates the levels of kynurenic acid in the brain. This compound has been implicated in several psychiatric and neurological disorders, such as schizophrenia and bipolar disorder. The modulation of kynurenic acid levels affects neurotransmission and synaptic plasticity by acting as an antagonist at N-methyl-D-aspartate (NMDA) and alpha-7 nicotinic acetylcholine receptors. PF-04859989 HCl shows potential applications in drug development for these conditions and related areas.

Reference

1. Bioorg Med Chem Lett. 2013 Apr 1;23(7):1961-6. doi: 10.1016/j.bmcl.2013.02.039.
Epub 2013 Feb 15.

PF-04859989 as a template for structure-based drug design: identification of new
pyrazole series of irreversible KAT II inhibitors with improved lipophilic
efficiency.

Dounay AB(1), Anderson M, Bechle BM, Evrard E, Gan X, Kim JY, McAllister LA,
Pandit J, Rong S, Salafia MA, Tuttle JB, Zawadzke LE, Verhoest PR.

Author information:
(1)Pfizer Worldwide Research and Development, Neuroscience Medicinal Chemistry,
Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA.


The structure-based design, synthesis, and biological evaluation of a new
pyrazole series of irreversible KAT II inhibitors are described herein. The
modification of the inhibitor scaffold of 1 and 2 from a dihydroquinolinone core
to a tetrahydropyrazolopyridinone core led to discovery of a new series of
potent KAT II inhibitors with excellent physicochemical properties. Compound 20
is the most potent and lipophilically efficient of these new pyrazole analogs,
with a k(inact)/K(i) value of 112,000 M(-1)s(-1) and lipophilic efficiency
(LipE) of 8.53. The X-ray crystal structure of 20 with KAT II demonstrates key
features that contribute to this remarkable potency and binding efficiency.