PF-2545920

PF-2545920

Systematic (IUPAC) name
2-(4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxymethyl)quinoline
Identifiers
CAS Number	1292799-56-4
PubChem	CID 11581936
DrugBank	DB08387
ChemSpider	9756702
UNII	R9Y8EY0G42
ChEMBL	CHEMBL1642569
Chemical data
Formula	C25H20N4O
Molar mass	392.453 g/mol
SMILES n3c1ccccc1ccc3COc5ccc(cc5)-c2nn(C)cc2-c4ccncc4
InChI InChI=1S/C25H20N4O/c1-29-16-23(18-12-14-26-15-13-18)25(28-29)20-7-10-22(11-8-20)30-17-21-9-6-19-4-2-3-5-24(19)27-21/h2-16H,17H2,1H3 Key:AZEXWHKOMMASPA-UHFFFAOYSA-N
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PF-2545920 is a drug developed by Pfizer for the treatment of schizophrenia. It acts as a phosphodiesterase inhibitor selective for the PDE10A subtype.^[1] 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.^[2] Older PDE_10A inhibitors such as papaverine have been shown to produce antipsychotic effects in animal models,^[3] 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.^[4] 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.^[5]

References

1. Verhoest PR, Chapin DS, Corman M, et al. (2009). "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". J. Med. Chem. 52 (16): 5188–96. doi:10.1021/jm900521k. PMID 19630403.
2. Verhoest 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.
3. 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. doi:10.1016/j.neuropharm.2006.04.013 PMID 16780899
4. 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
5. Carmen Drahl. Rethinking Schizophrenia. Chemical & Engineering News 2008 Sep 15; 86(37):38-40