PF-2545920
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| Identifiers | |
|---|---|
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| CAS Number |
898562-94-2  |
| PubChem (CID) | 11581936 |
| DrugBank |
DB08387 |
| ChemSpider |
9756702 |
| UNII |
R9Y8EY0G42 |
| ChEMBL |
CHEMBL1642569 |
| Chemical and physical data | |
| Formula | C25H20N4O |
| Molar mass | 392.453 g/mol |
| 3D model (Jmol) | Interactive image |
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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 PDE10A 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 PDE10A inhibitors such as papaverine have been shown to produce antipsychotic effects in animal models,[3] and more potent and selective PDE10A inhibitors are a current area of research for novel antipsychotic drugs which act through a different pathway to conventional dopamine or 5HT2A antagonist drugs and may have a more favourable side effects profile.[4] PF-2545920 is currently one of the furthest advanced PDE10A inhibitors in development and has progressed through to Phase II clinical trials in humans.[5]
References
- ↑ 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.
- ↑ 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.
- ↑ 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
- ↑ 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
- ↑ Carmen Drahl. Rethinking Schizophrenia. Chemical & Engineering News 2008 Sep 15; 86(37):38-40