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Updating {{drugbox}} (no changed fields - added verified revid - updated 'ChemSpiderID_Ref', 'DrugBank_Ref', 'UNII_Ref', 'ChEMBL_Ref', 'ChEBI_Ref', 'KEGG_Ref', 'StdInChI_Ref', 'StdInChIKey_Ref', 'DrugBank_Ref', 'ChEBI_Ref') per [[WP:CHEMVALID|Chem/Dr
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{{Short description|Chemical compound}}
{{Drugbox
{{Drugbox
| Verifiedfields = changed
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| verifiedrevid = 425127279
| Watchedfields = changed
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| IUPAC_name = 3-chloro-4-fluorophenyl-[4-fluoro-4-<nowiki>[[</nowiki>(5-methylpyrimidin-2-ylmethyl)amino]methyl]piperidin-1-yl]methanone
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| verifiedrevid = 451554460
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| image = F-15599-structure.png
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| IUPAC_name = 3-Chloro-4-fluorophenyl-[4-fluoro-4-<nowiki>[[</nowiki>(5-methylpyrimidin-2-ylmethyl)amino]methyl]piperidin-1-yl]methanone
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| image = F-15,599.svg


<!--Clinical data-->
<!--Clinical data-->
| tradename =
| tradename =
| pregnancy_category =
| pregnancy_category =
| legal_status = Uncontrolled
| legal_status = Investigational
| routes_of_administration = Oral
| routes_of_administration = Oral


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| metabolism =
| metabolism =
| elimination_half-life =
| elimination_half-life =
| excretion =
| excretion =


<!--Identifiers-->
<!--Identifiers-->
| CAS_number = ?
| IUPHAR_ligand = 3924
| CAS_number_Ref = {{cascite|correct|CAS}}
| ATC_prefix = none
| CAS_number=635323-95-4
| ATC_suffix =
| UNII_Ref = {{fdacite|correct|FDA}}
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| PubChem = ?
| UNII = 83481Y1YCX
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 9916065
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| PubChem = 11741361


<!--Chemical data-->
<!--Chemical data-->
| C=19 | H=22 | Cl=1 | F=2 | N=4 | O=1
| C=19 | H=22 | Cl=1 | F=2 | N=4 | O=1
| molecular_weight = 395.854 g/mol
| smiles = Cc3cnc(nc3)CNCC(F)(CC2)CCN2C(=O)c(cc1Cl)ccc1F
| smiles = Cc3cnc(nc3)CNCC(F)(CC2)CCN2C(=O)c(cc1Cl)ccc1F
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C19H21ClF2N4O/c1-13-9-24-17(25-10-13)11-23-12-19(22)4-6-26(7-5-19)18(27)14-2-3-16(21)15(20)8-14/h2-3,8-10,23H,4-7,11-12H2,1H3
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = WAAXKNFGOFTGLP-UHFFFAOYSA-N
}}
}}


'''F-15,599''' is a very [[potency (pharmacology)|potent]] and highly [[binding selectivity|selective]] [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]] [[full agonist]].<ref name="pmid17803293">{{cite journal | author = Maurel JL, Autin JM, Funes P, Newman-Tancredi A, Colpaert F, Vacher B | title = High-efficacy 5-HT1A agonists for antidepressant treatment: a renewed opportunity | journal = Journal of Medicinal Chemistry | volume = 50 | issue = 20 | pages = 5024–33 | year = 2007 | month = October | pmid = 17803293 | doi = 10.1021/jm070714l }}</ref><ref name="pmid19154445">{{cite journal | author = Newman-Tancredi A, Martel JC, Assié MB, ''et al.'' | title = Signal transduction and functional selectivity of F15599, a preferential post-synaptic 5-HT1A receptor agonist | journal = British Journal of Pharmacology | volume = 156 | issue = 2 | pages = 338–53 | year = 2009 | month = January | pmid = 19154445 | pmc = 2697830 | doi = 10.1111/j.1476-5381.2008.00001.x }}</ref> It displays [[functional selectivity]] by strongly activating 5-HT<sub>1A</sub> receptors in the [[prefrontal cortex]] while having little effect on [[autoreceptor]]s in the [[raphe nucleus]].<ref name="pmid17803293">{{cite journal | author = Maurel JL, Autin JM, Funes P, Newman-Tancredi A, Colpaert F, Vacher B | title = High-efficacy 5-HT1A agonists for antidepressant treatment: a renewed opportunity | journal = Journal of Medicinal Chemistry | volume = 50 | issue = 20 | pages = 5024–33 | year = 2007 | month = October | pmid = 17803293 | doi = 10.1021/jm070714l }}</ref><ref name="pmid19154445">{{cite journal | author = Newman-Tancredi A, Martel JC, Assié MB, ''et al.'' | title = Signal transduction and functional selectivity of F15599, a preferential post-synaptic 5-HT1A receptor agonist | journal = British Journal of Pharmacology | volume = 156 | issue = 2 | pages = 338–53 | year = 2009 | month = January | pmid = 19154445 | pmc = 2697830 | doi = 10.1111/j.1476-5381.2008.00001.x }}</ref> As a result, it has been touted as a preferential [[postsynaptic]] 5-HT<sub>1A</sub> receptor agonist and is being investigated as a novel potential [[antidepressant]].<ref name="pmid17803293">{{cite journal | author = Maurel JL, Autin JM, Funes P, Newman-Tancredi A, Colpaert F, Vacher B | title = High-efficacy 5-HT1A agonists for antidepressant treatment: a renewed opportunity | journal = Journal of Medicinal Chemistry | volume = 50 | issue = 20 | pages = 5024–33 | year = 2007 | month = October | pmid = 17803293 | doi = 10.1021/jm070714l }}</ref><ref name="pmid19154445">{{cite journal | author = Newman-Tancredi A, Martel JC, Assié MB, ''et al.'' | title = Signal transduction and functional selectivity of F15599, a preferential post-synaptic 5-HT1A receptor agonist | journal = British Journal of Pharmacology | volume = 156 | issue = 2 | pages = 338–53 | year = 2009 | month = January | pmid = 19154445 | pmc = 2697830 | doi = 10.1111/j.1476-5381.2008.00001.x }}</ref>
'''F-15,599''', also known as '''NLX-101''', is a [[potency (pharmacology)|potent]] and [[binding selectivity|selective]] [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]] [[full agonist]].<ref name="pmid17803293">{{cite journal |vauthors=Maurel JL, Autin JM, Funes P, Newman-Tancredi A, Colpaert F, Vacher B |title=High-efficacy 5-HT1A agonists for antidepressant treatment: a renewed opportunity |journal=Journal of Medicinal Chemistry |volume=50 |issue=20 |pages=5024–33 | date=October 2007 |pmid=17803293 |doi=10.1021/jm070714l}}</ref><ref name="pmid19154445">{{cite journal |vauthors=Newman-Tancredi A, Martel JC, Assié MB |title=Signal transduction and functional selectivity of F15599, a preferential post-synaptic 5-HT1A receptor agonist |journal=British Journal of Pharmacology |volume=156 |issue=2 |pages=338–53 | date=January 2009 |pmid=19154445 |pmc=2697830 |doi=10.1111/j.1476-5381.2008.00001.x|display-authors=etal}}</ref> It displays [[functional selectivity]] (also known as "biased agonism") by strongly activating 5-HT<sub>1A</sub> receptors in the [[postsynaptic]] [[prefrontal cortex]] while having little effect on [[somatodendritic]] [[autoreceptor]]s in the [[raphe nucleus]].<ref name=pmid17803293 /><ref name=pmid19154445 /> As a result, it has been touted as a preferential postsynaptic 5-HT<sub>1A</sub> receptor agonist and has been investigated as a novel potential [[antidepressant]].<ref name= pmid17803293/><ref name=pmid19154445 /><ref>{{cite journal |vauthors=Assié MB, Bardin L, Auclair AL |title=F15599, a highly selective post-synaptic 5-HT(1A) receptor agonist: in-vivo profile in behavioural models of antidepressant and serotonergic activity |journal=The International Journal of Neuropsychopharmacology |volume=13 |issue=10 |pages=1285–98 | date=November 2010 |pmid=20059805 |doi=10.1017/S1461145709991222|display-authors=etal|doi-access=free }}</ref>


In cognitive tests in rodent, F-15,599 attenuates memory deficits elicited by the NMDA receptor antagonist PCP, suggesting that it may improve cognitive function in disorders such as schizophrenia.<ref>{{cite journal |vauthors=Depoortère R, Auclair AL, Bardin L, Colpaert FC, Vacher B, Newman-Tancredi A |title=F15599, a preferential post-synaptic 5-HT1A receptor agonist: activity in models of cognition in comparison with reference 5-HT1A receptor agonists |journal=European Neuropsychopharmacology |volume=20 |issue=9 |pages=641–54 | date=September 2010 |pmid=20488670 |doi=10.1016/j.euroneuro.2010.04.005|s2cid=22222213 }}</ref>
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== See also ==

A subsequent study showed that F-15,599 reduces breathing irregularity and apneas observed in mice with mutations of the MeCP2 gene.<ref>{{cite journal |vauthors=Levitt ES, Hunnicutt BJ, Knopp SJ, Williams JT, Bissonnette JM |title=A selective 5-HT1a receptor agonist improves respiration in a mouse model of Rett syndrome |journal=Journal of Applied Physiology |volume=115 |issue=11 |pages=1626–33 | date=December 2013 |pmid=24092697 |doi=10.1152/japplphysiol.00889.2013 |pmc=3882741}}</ref> Dysruption of MeCP2 gene expression underlies [[Rett syndrome]], a debilitating neurodevelopmental [[orphan disease]].

F-15,599 was discovered and initially developed by [[Pierre Fabre Group|Pierre Fabre Médicament]], a French pharmaceuticals company. In September 2013, F-15,599 was out-licensed to [[Neurolixis]], a California-based biotechnology company. Neurolixis announced that it intends to re-purpose F-15,599 for the treatment of [[Rett syndrome]].<ref>http://neurolixis.com/images/stories/nlx_pf_license_23sept13.pdf{{full citation needed|date=June 2015}}</ref> and obtained [[orphan drug]] designation from the United States [[Food and Drug Administration]] (FDA)<ref>{{Cite web|url=http://www.accessdata.fda.gov/scripts/opdlisting/oopd/OOPD_Results_2.cfm?Index_Number=410613|title=Enforcement Reports|access-date=2014-03-03|archive-date=2015-02-24|archive-url=https://web.archive.org/web/20150224233953/http://www.accessdata.fda.gov/scripts/opdlisting/oopd/OOPD_Results_2.cfm?Index_Number=410613|url-status=dead}}</ref> and from the European Commission for this indication.<ref>{{Cite web|url=http://ec.europa.eu/health/documents/community-register/html/o1242.htm|title = Public Health - European Commission}}</ref>

Researchers at the [[University of Bristol]] are investigating the activity of F-15599 in animal models of Rett Syndrome, with support from the International Rett Syndrome Foundation.<ref>{{Cite web|url=http://www.bristol.ac.uk/news/2014/april/rett-syndrome-research.html|title = April: Rett syndrome research &#124; News and features &#124; University of Bristol}}</ref> In June 2015, the Rett Syndrome Research Trust awarded a grant to Neurolixis to advance F-15599 to clinical development.<ref>{{Cite web|url=https://rettsyndrome.wordpress.com/2015/06/24/rsrt-awards-530000-to-neurolixis-for-clinical-development-of-nlx-101/|title = RSRT Awards $530,000 to Neurolixis for Clinical Development of NLX-101|date = 24 June 2015}}</ref>

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==See also==
* [[Befiradol]] (F-13,640)
* [[Befiradol]] (F-13,640)
* [[Eptapirone]] (F-11,440)
* [[Eptapirone]] (F-11,440)


== References ==
==References==
{{Reflist}}
{{Reflist|2}}


==External links==
* [http://adisinsight.springer.com/drugs/800041224 F-15599 - AdisInsight]


{{Antidepressants}}
{{Antidepressants}}
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[[Category:Piperidines]]
[[Category:Piperidines]]
[[Category:Pyrimidines]]
[[Category:Pyrimidines]]
[[Category:Amides]]
[[Category:Benzamides]]
[[Category:Organochlorides]]
[[Category:Chloroarenes]]
[[Category:Organofluorides]]
[[Category:Organofluorides]]
[[Category:5-HT1A agonists]]

[[Category:Fluoroarenes]]

{{nervous-system-drug-stub}}
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