Mardepodect

Mardepodect
Clinical data
Other names	PF-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	898562-94-2 ;
PubChem CID	11581936;
DrugBank	DB08387 ;
ChemSpider	9756702 ;
UNII	R9Y8EY0G42;
KEGG	D11171;
ChEMBL	ChEMBL1642569 ;
CompTox Dashboard (EPA)	DTXSID001025873 ;
Chemical and physical data
Formula	C25H20N4O
Molar mass	392.462 g·mol−1
3D 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 ; Key:AZEXWHKOMMASPA-UHFFFAOYSA-N ;
	(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.

[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.

[AdisInsight-6] "Mardepodect". AdisInsight. Springer Nature Switzerland AG.

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Mardepodect

See also

References