Mardepodect

Drug formerly in development

None

Legal statusLegal status

Investigational

Identifiers

IUPAC name

2-(4-(1-Methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxymethyl)quinoline

CAS Number

898562-94-2^N

PubChem CID

11581936

DrugBank

DB08387^N

ChemSpider

9756702^N

UNII

R9Y8EY0G42

KEGG

D11171

ChEMBL

ChEMBL1642569^N

CompTox Dashboard (EPA)

DTXSID001025873

Chemical and physical dataFormulaC₂₅H₂₀N₄OMolar mass392.462 g·mol⁻¹3D model (JSmol)

Interactive image

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)

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 PDE_10A 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 5-HT_2A antagonist drugs and may have a more favourable side effects profile.^[4] Mardepodect is currently one of the furthest advanced PDE_10A 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]

References

^ 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.
^ 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
^ 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.
^ 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.
^ Drahl, C (15 September 2008). "Rethinking Schizophrenia". Chemical & Engineering News. 86 (37): 38–40. doi:10.1021/cen-v086n037.p038.
^ "Mardepodect". AdisInsight. Springer Nature Switzerland AG.