PF-2545920

Drugbox
IUPAC_name = 2-(4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxymethyl)quinoline

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PubChem = 11581936
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C=25|H=20|N=4|O=1
molecular_weight = 392.453 g/mol
smiles = n3c1ccccc1ccc3COc5ccc(cc5)-c2nn(C)cc2-c4ccncc4
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PF-2545920 is a drug developed by Pfizer for the treatment of schizophrenia. It acts as a selective phosphodiesterase inhibitor selective for the PDE_10A subtype. The PDE_10A enzyme is expressed primarily in the brain, mostly in the striatum, nucleus accumbens and olfactory tubercle, and is thought to be particularly important in regulating the activity of dopamine-sensitive medium spiny neurons in the striatum which are known to be targets of conventional antipsychotic drugs. [Vorhoest PR, Proulx C. Pfizer Global Research & Development. Succinate Salt of 2-(4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxymethyl)quinoline. WIPO Patent WO 2008/084299 A1.] Older PDE_10A inhibitors such as papaverine have been shown to produce antipsychotic effects in animal models, [Siuciak JA, Chapin DS, Harms JF, Lebel LA, McCarthy SA, Chambers L, Shrikhande A, Wong S, Menniti FS, Schmidt CJ. Inhibition of the striatum-enriched phosphodiesterase PDE10A: a novel approach to the treatment of psychosis. "Neuropharmacology". 2006 Aug;51(2):386-96. PMID 16780899] and more potent and selective PDE_10A inhibitors are a current area of research for novel antipsychotic drugs which act through a different pathway to conventional dopamine or 5HT_2A antagonist drugs and may have a more favourable side effects profile. [Schmidt CJ, Chapin DS, Cianfrogna J, Corman ML, Hajos M, Harms JF, Hoffman WE, Lebel LA, McCarthy SA, Nelson FR, Proulx-LaFrance C, Majchrzak MJ, Ramirez AD, Schmidt K, Seymour PA, Siuciak JA, Tingley FD 3rd, Williams RD, Verhoest PR, Menniti FS. Preclinical characterization of selective phosphodiesterase 10A inhibitors: a new therapeutic approach to the treatment of schizophrenia. "Journal of Pharmacology and Experimental Therapeutics". 2008 May;325(2):681-90. PMID 18287214] PF-2545920 is currently one of the furthest advanced PDE_10A inhibitors in development and has progressed through to Phase II clinical trials in humans. [ [http://pubs.acs.org/cen/science/86/8637sci2.html Carmen Drahl. Rethinking Schizophrenia. "Chemical & Engineering News" 2008 Sep 15; 86(37):38-40] ]

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