Synonym
APD125; APD-125; APD 125; Nelotanserin
IUPAC/Chemical Name
1-(3-(4-bromo-1-methyl-1H-pyrazol-5-yl)-4-methoxyphenyl)-3-(2,4-difluorophenyl)urea
InChi Key
COSPVUFTLGQDQL-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
O=C(NC1=CC=C(F)C=C1F)NC2=CC=C(OC)C(C3=C(Br)C=NN3C)=C2
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Nelotanserin is a potent 5-HT2A inverse agonist, a moderately potent 5-HT2C partial inverse agonist and a weak 5-HT2B inverse agonist, with IC50s of 1.7, 79, 791 nM in IP accumulation assays, respectively.
In vivo activity:
Individual doses were selected for each of the four compounds to measure their effects in rat sleep pharmacology studies that were 2-fold higher than the compound’s ED50 in the DOI model. The delta power during non-REM sleep (NREMS) was significantly different between all the analogues tested and the vehicle control (Figure 3). Compound 39 (Nelotanserin) produced significant increases in delta power that persisted for the first 4 h following dosing. No significant effects were found on either waking bout length or number of waking bouts. Significant differences were found, however, in NREMS bout length. Compound 39 significantly increased NREMS bout length during the first hour following dosing, and 3 did so during the second hour. In conjunction with this increased NREM bout duration, the number of NREM bouts decreased during the first hour for compound 39 (p < 0.01) as well as for compound 15 (p < 0.05).
Reference: J Med Chem. 2010 Mar 11;53(5):1923-36. https://pubmed.ncbi.nlm.nih.gov/20143782/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
32.0 |
73.20 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
437.24
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Teegarden BR, Li H, Jayakumar H, Strah-Pleynet S, Dosa PI, Selaya SD, Kato N, Elwell KH, Davidson J, Cheng K, Saldana H, Frazer JM, Whelan K, Foster J, Espitia S, Webb RR, Beeley NR, Thomsen W, Morairty SR, Kilduff TS, Al-Shamma HA. 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. J Med Chem. 2010 Mar 11;53(5):1923-36. doi: 10.1021/jm9007328. PMID: 20143782.
In vivo protocol:
1. Teegarden BR, Li H, Jayakumar H, Strah-Pleynet S, Dosa PI, Selaya SD, Kato N, Elwell KH, Davidson J, Cheng K, Saldana H, Frazer JM, Whelan K, Foster J, Espitia S, Webb RR, Beeley NR, Thomsen W, Morairty SR, Kilduff TS, Al-Shamma HA. 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. J Med Chem. 2010 Mar 11;53(5):1923-36. doi: 10.1021/jm9007328. PMID: 20143782.
1: Monti JM. Serotonin control of sleep-wake behavior. Sleep Med Rev. 2011
Aug;15(4):269-81. doi: 10.1016/j.smrv.2010.11.003. Epub 2011 Apr 2. Review.
PubMed PMID: 21459634.
2: Teegarden BR, Li H, Jayakumar H, Strah-Pleynet S, Dosa PI, Selaya SD, Kato N,
Elwell KH, Davidson J, Cheng K, Saldana H, Frazer JM, Whelan K, Foster J, Espitia
S, Webb RR, Beeley NR, Thomsen W, Morairty SR, Kilduff TS, Al-Shamma HA.
Discovery of
1-[3-(4-bromo-2-methyl-2h-pyrazol-3-yl)-4-methoxyphenyl]-3-(2,4-difluorophenyl)ur
ea (nelotanserin) and related 5-hydroxytryptamine2A inverse agonists for the
treatment of insomnia. J Med Chem. 2010 Mar 11;53(5):1923-36. doi:
10.1021/jm9007328. PubMed PMID: 20143782.
3: Al-Shamma HA, Anderson C, Chuang E, Luthringer R, Grottick AJ, Hauser E,
Morgan M, Shanahan W, Teegarden BR, Thomsen WJ, Behan D. Nelotanserin, a novel
selective human 5-hydroxytryptamine2A inverse agonist for the treatment of
insomnia. J Pharmacol Exp Ther. 2010 Jan;332(1):281-90. doi:
10.1124/jpet.109.160994. Epub 2009 Oct 19. PubMed PMID: 19841476.
