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PDBsum entry 3hqw
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Hydrolase/hydrolase inhibitor
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PDB id
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3hqw
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References listed in PDB file
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Key reference
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Title
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Discovery of a novel class of phosphodiesterase 10a inhibitors and identification of clinical candidate 2-[4-(1-Methyl-4-Pyridin-4-Yl-1h-Pyrazol-3-Yl)-Phenoxymethyl]-Quinoline (pf-2545920) for the treatment of schizophrenia.
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Authors
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P.R.Verhoest,
D.S.Chapin,
M.Corman,
K.Fonseca,
J.F.Harms,
X.Hou,
E.S.Marr,
F.S.Menniti,
F.Nelson,
R.O'Connor,
J.Pandit,
C.Proulx-Lafrance,
A.W.Schmidt,
C.J.Schmidt,
J.A.Suiciak,
S.Liras.
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Ref.
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J Med Chem, 2009,
52,
5188-5196.
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PubMed id
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Abstract
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By utilizing structure-based drug design (SBDD) knowledge, a novel class of
phosphodiesterase (PDE) 10A inhibitors was identified. The structure-based drug
design efforts identified a unique "selectivity pocket" for PDE10A inhibitors,
and interactions within this pocket allowed the design of highly selective and
potent PDE10A inhibitors. Further optimization of brain penetration and
drug-like properties led to the discovery of
2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline
(PF-2545920). This PDE10A inhibitor is the first reported clinical entry for
this mechanism in the treatment of schizophrenia.
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