Nelotanserin

Nelotanserin
Clinical data
Other names	APD-125
Routes of; administration	Oral
ATC code	none;
Identifiers
	IUPAC name 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxyphenyl]-3-(2,4-difluorophenyl)urea;
CAS Number	839713-36-9 ;
PubChem CID	11683556;
ChemSpider	9858284 ;
UNII	4ZA73QEW2P;
KEGG	D09645;
CompTox Dashboard (EPA)	DTXSID40232868 ;
Chemical and physical data
Formula	C18H15BrF2N4O2
Molar mass	437.245 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Brc1cnn(C)c1-c2cc(ccc2OC)NC(=O)Nc3ccc(F)cc3F;
	InChI InChI=1S/C18H15BrF2N4O2/c1-25-17(13(19)9-22-25)12-8-11(4-6-16(12)27-2)23-18(26)24-15-5-3-10(20)7-14(15)21/h3-9H,1-2H3,(H2,23,24,26) ; Key:COSPVUFTLGQDQL-UHFFFAOYSA-N ;
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Nelotanserin (former developmental code name APD-125) is a drug developed by Arena Pharmaceuticals which acts as an inverse agonist on the serotonin receptor subtype 5-HT_2A and was under development for the treatment of insomnia.[1] It was shown to be effective and well tolerated in clinical trials,[2][3] but development was halted in December 2008 because the substance did not meet the trial's effectiveness endpoints.[4] Research continues on newer analogues which may potentially be more successful.[5] More recently, nelotanserin has been repurposed for the treatment of Lewy body disease.[6] As of 2017, it is in phase II clinical trials for this indication.[6]

References

Teegarden BR, Li H, Jayakumar H, Strah-Pleynet S, Dosa PI, Selaya SD, et al. (March 2010). "Discovery of 1-[3-(4-bromo-2-methyl-2h-pyrazol-3-yl)-4-methoxyphenyl]-3-(2,4-difluorophenyl)urea (nelotanserin) and related 5-hydroxytryptamine2A inverse agonists for the treatment of insomnia". Journal of Medicinal Chemistry. 53 (5): 1923–36. doi:10.1021/jm9007328. PMID 20143782.
Rosenberg R, Seiden DJ, Hull SG, Erman M, Schwartz H, Anderson C, et al. (December 2008). "APD125, a selective serotonin 5-HT(2A) receptor inverse agonist, significantly improves sleep maintenance in primary insomnia". Sleep. 31 (12): 1663–71. doi:10.1093/sleep/31.12.1663. PMC 2603489. PMID 19090322.
Al-Shamma HA, Anderson C, Chuang E, Luthringer R, Grottick AJ, Hauser E, et al. (January 2010). "Nelotanserin, a novel selective human 5-hydroxytryptamine2A inverse agonist for the treatment of insomnia". The Journal of Pharmacology and Experimental Therapeutics. 332 (1): 281–90. doi:10.1124/jpet.109.160994. PMID 19841476. S2CID 2759858.
"APD125 for Insomnia". Arena Pharmaceuticals, Inc. Archived from the original on 2009-08-26.
Xiong Y, Ullman B, Choi JS, Cherrier M, Strah-Pleynet S, Decaire M, et al. (August 2010). "Synthesis and in vivo evaluation of phenethylpiperazine amides: selective 5-hydroxytryptamine(2A) receptor antagonists for the treatment of insomnia". Journal of Medicinal Chemistry. 53 (15): 5696–706. doi:10.1021/jm100479q. PMID 20684606.
"Nelotanserin - Axovant Gene Therapies". Adis International Ltd. Springer Science+Business Media.

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[1] Teegarden BR, Li H, Jayakumar H, Strah-Pleynet S, Dosa PI, Selaya SD, et al. (March 2010). "Discovery of 1-[3-(4-bromo-2-methyl-2h-pyrazol-3-yl)-4-methoxyphenyl]-3-(2,4-difluorophenyl)urea (nelotanserin) and related 5-hydroxytryptamine2A inverse agonists for the treatment of insomnia". Journal of Medicinal Chemistry. 53 (5): 1923–36. doi:10.1021/jm9007328. PMID 20143782.

[2] Rosenberg R, Seiden DJ, Hull SG, Erman M, Schwartz H, Anderson C, et al. (December 2008). "APD125, a selective serotonin 5-HT(2A) receptor inverse agonist, significantly improves sleep maintenance in primary insomnia". Sleep. 31 (12): 1663–71. doi:10.1093/sleep/31.12.1663. PMC 2603489. PMID 19090322.

[3] Al-Shamma HA, Anderson C, Chuang E, Luthringer R, Grottick AJ, Hauser E, et al. (January 2010). "Nelotanserin, a novel selective human 5-hydroxytryptamine2A inverse agonist for the treatment of insomnia". The Journal of Pharmacology and Experimental Therapeutics. 332 (1): 281–90. doi:10.1124/jpet.109.160994. PMID 19841476. S2CID 2759858.

[4] "APD125 for Insomnia". Arena Pharmaceuticals, Inc. Archived from the original on 2009-08-26.

[5] Xiong Y, Ullman B, Choi JS, Cherrier M, Strah-Pleynet S, Decaire M, et al. (August 2010). "Synthesis and in vivo evaluation of phenethylpiperazine amides: selective 5-hydroxytryptamine(2A) receptor antagonists for the treatment of insomnia". Journal of Medicinal Chemistry. 53 (15): 5696–706. doi:10.1021/jm100479q. PMID 20684606.

[AdisInsight-6] "Nelotanserin - Axovant Gene Therapies". Adis International Ltd. Springer Science+Business Media.