Mardepodect

Mardepodect (developmental code name PF-2545920) is a drug which was 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 5-HT2A antagonist drugs and may have a more favourable side effects profile.[4] Mardepodect is currently one of the furthest advanced PDE10A inhibitors in development and has progressed through to Phase II clinical trials in humans.[5] In 2017, development of mardepodect for the treatment of schizophrenia and Huntington's disease was discontinued.[6]

Mardepodect
Clinical data
Other namesPDF-2545920
ATC code
  • None
Legal status
Legal status
  • Investigational
Identifiers
IUPAC name
  • 2-(4-(1-Methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxymethyl)quinoline
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC25H20N4O
Molar mass392.462 g·mol−1
3D model (JSmol)
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 N
  • Key:AZEXWHKOMMASPA-UHFFFAOYSA-N N
 NY (what is this?)  (verify)

References
  1. Verhoest PR, Chapin DS, Corman M, Fonseca K, Harms JF, Hou X, et al. (August 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". Journal of Medicinal Chemistry. 52 (16): 5188–96. doi:10.1021/jm900521k. PMID 19630403.
  2. CA 2673435 C, Vorhoest, Patrick Robert & Proulx, Caroline, "Succinate salt of 2-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl) phenoxy)methyl)quinoline", published 2008-07-17
  3. Siuciak JA, Chapin DS, Harms JF, Lebel LA, McCarthy SA, Chambers L, et al. (August 2006). "Inhibition of the striatum-enriched phosphodiesterase PDE10A: a novel approach to the treatment of psychosis". Neuropharmacology. 51 (2): 386–96. doi:10.1016/j.neuropharm.2006.04.013. PMID 16780899. S2CID 13447370.
  4. Schmidt CJ, Chapin DS, Cianfrogna J, Corman ML, Hajos M, Harms JF, et al. (May 2008). "Preclinical characterization of selective phosphodiesterase 10A inhibitors: a new therapeutic approach to the treatment of schizophrenia" (PDF). The Journal of Pharmacology and Experimental Therapeutics. 325 (2): 681–90. doi:10.1124/jpet.107.132910. PMID 18287214. S2CID 12103458.
  5. Drahl, C (15 September 2008). "Rethinking Schizophrenia". Chemical & Engineering News. 86 (37): 38–40. doi:10.1021/cen-v086n037.p038.
  6. "Mardepodect". AdisInsight. Springer Nature Switzerland AG.
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