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{{Short description|Drug formerly in development}}

{{Drugbox
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| Watchedfields = changed
| verifiedrevid = 424942725
| verifiedrevid = 424942725
| IUPAC_name = 2-(4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxymethyl)quinoline
| IUPAC_name = 2-(4-(1-Methyl-4-pyridin-4-yl-1''H''-pyrazol-3-yl)phenoxymethyl)quinoline
| image = PF2545920.png
| image = PF-2545920.svg


<!--Clinical data-->
<!--Clinical data-->
| tradename =
| tradename =
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category =
| pregnancy_category =
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status =
| legal_status = Investigational
| routes_of_administration =
| routes_of_administration =


<!--Pharmacokinetic data-->
<!--Pharmacokinetic data-->
| bioavailability =
| bioavailability =
| protein_bound =
| protein_bound =
| metabolism =
| metabolism =
| elimination_half-life =
| elimination_half-life =
| excretion =
| excretion =


<!--Identifiers-->
<!--Identifiers-->
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number =
| CAS_number = 898562-94-2
| ATC_prefix =
| ATC_suffix =
| ATC_prefix = None
| ATC_suffix =
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1642569
| ChEMBL = 1642569
| PubChem = 11581936
| PubChem = 11581936
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = R9Y8EY0G42
| UNII = R9Y8EY0G42
| KEGG = D11171
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank =
| DrugBank = DB08387
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 9756702
| synonyms = PF-2545920


<!--Chemical data-->
<!--Chemical data-->
| C=25 | H=20 | N=4 | O=1
| C=25 | H=20 | N=4 | O=1
⚫
| SMILES = n3c1ccccc1ccc3COc5ccc(cc5)-c2nn(C)cc2-c4ccncc4
| molecular_weight = 392.453 g/mol
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
⚫
| smiles = n3c1ccccc1ccc3COc5ccc(cc5)-c2nn(C)cc2-c4ccncc4
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = AZEXWHKOMMASPA-UHFFFAOYSA-N
}}
}}


'''PF-2545920''' is a drug developed by [[Pfizer]] for the treatment of [[schizophrenia]]. It acts as a [[phosphodiesterase inhibitor]] selective for the PDE<sub>10A</sub> subtype. The PDE<sub>10A</sub> 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.<ref>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.</ref> Older PDE<sub>10A</sub> inhibitors such as [[papaverine]] have been shown to produce antipsychotic effects in animal models,<ref>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</ref> and more potent and selective PDE<sub>10A</sub> inhibitors are a current area of research for novel antipsychotic drugs which act through a different pathway to conventional dopamine or 5HT<sub>2A</sub> antagonist drugs and may have a more favourable side effects profile.<ref>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</ref> PF-2545920 is currently one of the furthest advanced PDE<sub>10A</sub> inhibitors in development and has progressed through to Phase II [[clinical trials]] in humans.<ref>[http://pubs.acs.org/cen/science/86/8637sci2.html Carmen Drahl. Rethinking Schizophrenia. ''Chemical & Engineering News'' 2008 Sep 15; 86(37):38-40]</ref>
'''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|PDE<sub>10A</sub>]] subtype.<ref>{{cite journal | vauthors = Verhoest PR, Chapin DS, Corman M, Fonseca K, Harms JF, Hou X, Marr ES, Menniti FS, Nelson F, O'Connor R, Pandit J, Proulx-Lafrance C, Schmidt AW, Schmidt CJ, Suiciak JA, Liras S | display-authors = 6 | title = 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 = Journal of Medicinal Chemistry | volume = 52 | issue = 16 | pages = 5188–96 | date = August 2009 | pmid = 19630403 | doi = 10.1021/jm900521k }}</ref> The PDE<sub>10A</sub> 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.<ref>{{cite patent | country = CA | number = 2673435 C | status = | title = Succinate salt of 2-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl) phenoxy)methyl)quinoline | pubdate = 2008-07-17 | fdate = 2007-12-03 | pridate = 2006-12-21 | invent1 = Vorhoest | inventor1-first = Patrick Robert | invent2 = Proulx | inventor2-first = Caroline | assign1 = | assign2 = |class = | url = http://www.google.co.in/patents/CA2673435A1}}</ref> Older PDE<sub>10A</sub> inhibitors such as [[papaverine]] have been shown to produce antipsychotic effects in animal models,<ref>{{cite journal | vauthors = Siuciak JA, Chapin DS, Harms JF, Lebel LA, McCarthy SA, Chambers L, Shrikhande A, Wong S, Menniti FS, Schmidt CJ | display-authors = 6 | title = Inhibition of the striatum-enriched phosphodiesterase PDE10A: a novel approach to the treatment of psychosis | journal = Neuropharmacology | volume = 51 | issue = 2 | pages = 386–96 | date = August 2006 | pmid = 16780899 | doi = 10.1016/j.neuropharm.2006.04.013 | s2cid = 13447370 }}</ref> and more potent and selective PDE<sub>10A</sub> inhibitors are a current area of research for novel antipsychotic drugs which act through a different pathway to conventional dopamine or [[5-HT2A receptor|5-HT<sub>2A</sub>]] antagonist drugs and may have a more favourable side effects profile.<ref>{{cite journal | vauthors = 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, Williams RD, Verhoest PR, Menniti FS | display-authors = 6 | title = Preclinical characterization of selective phosphodiesterase 10A inhibitors: a new therapeutic approach to the treatment of schizophrenia | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 325 | issue = 2 | pages = 681–90 | date = May 2008 | pmid = 18287214 | doi = 10.1124/jpet.107.132910 | s2cid = 12103458 | url = http://jpet.aspetjournals.org/content/jpet/325/2/681.full.pdf }}</ref> Mardepodect is currently one of the furthest advanced PDE<sub>10A</sub> inhibitors in development and has progressed through to Phase II [[clinical trials]] in humans.<ref>{{cite journal | last1 = Drahl | first1 = C | title = Rethinking Schizophrenia | journal = Chemical & Engineering News | date = 15 September 2008 | volume = 86 | issue = 37 | pages = 38–40 | doi = 10.1021/cen-v086n037.p038}}</ref> In 2017, development of mardepodect for the treatment of schizophrenia and [[Huntington's disease]] was discontinued.<ref name="AdisInsight">{{cite web |url= https://adisinsight.springer.com/drugs/800025561|title=Mardepodect | work = AdisInsight | publisher = Springer Nature Switzerland AG }}</ref>


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== References ==

{{reflist}}

⚫
==References==
<references/>


{{Phosphodiesterase inhibitors}}
{{Phosphodiesterase inhibitors}}


⚫
[[Category:Abandoned drugs]]
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[[Category:Drugs developed by Pfizer]]
⚫
[[Category:Phenol ethers]]
[[Category:Phosphodiesterase inhibitors]]
[[Category:Phosphodiesterase inhibitors]]
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[[Category:Pyrazoles]]
[[Category:4-Pyridyl compounds]]
[[Category:Quinolines]]
[[Category:Quinolines]]
⚫
[[Category:Phenol ethers]]
⚫
[[Category:Pyrazoles]]
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[[Category:Pyridines]]
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[[Category:Pfizer]]

Latest revision as of 01:45, 22 August 2024

Mardepodect
Clinical data
Other namesPF-2545920
ATC code
  • None
Legal status
Legal status
  • Investigational
Identifiers
  • 2-(4-(1-Methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxymethyl)quinoline
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC25H20N4O
Molar mass392.462 g·mol−1
3D model (JSmol)
  • n3c1ccccc1ccc3COc5ccc(cc5)-c2nn(C)cc2-c4ccncc4
  • 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
 ☒NcheckY (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 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]

References

[edit]
  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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