A-971432

A-971432
	Ball and stick structure of A-971432
Identifiers
	IUPAC name 1-(4-((3,4-Dichlorobenzyl)oxy)benzyl)azetidine-3-carboxylic acid;
CAS Number	1240308-45-5;
PubChem CID	46872626;
ChemSpider	35523147 ;
CompTox Dashboard (EPA)	DTXSID301045800 ;
Chemical and physical data
Formula	C18H17Cl2NO3
Molar mass	366.24 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1C(CN1CC2=CC=C(C=C2)OCC3=CC(=C(C=C3)Cl)Cl)C(=O)O;
	InChI InChI=1S/C18H17Cl2NO3/c19-16-6-3-13(7-17(16)20)11-24-15-4-1-12(2-5-15)8-21-9-14(10-21)18(22)23/h1-7,14H,8-11H2,(H,22,23); Key:WAAWETUDFSIYSD-UHFFFAOYSA-N;
	(what is this?)

A-971432 is an orally bioavailable selective agonist of sphingosine-1-phosphate receptor 5 (S1PR5) discovered at AbbVie.^[1] It was discovered using high-throughput chemistry.^[2] S1P5 agonists have been proposed as an innovative mechanism for the treatment of neurodegenerative disorders such as Alzheimer's disease and lysosomal storage disorders such as Niemann–Pick disease.^[3] Stimulation of S1PR5 with A-971432 has been shown to preserve blood-brain barrier integrity and exert a therapeutic effect in an animal model of Huntington’s disease.^[4]

References

^ WO application 2010093704, AbbVie, "Preparation of 1-benzylazetidine-3-carboxylic acid derivatives as agonists and antagonists of the S1P5 receptor", published 2010-08-19
^ Hobson AD, Harris CM, van der Kam EL, Turner SC, Abibi A, Aguirre AL, Bousquet P, Kebede T, Konopacki DB, Gintant G, Kim Y, Larson K, Maull JW, Moore NS, Shi D, Shrestha A, Tang X, Zhang P, Sarris KK (Nov 2015). "Discovery of A-971432, An Orally Bioavailable Selective Sphingosine-1-Phosphate Receptor 5 (S1P5) Agonist for the Potential Treatment of Neurodegenerative Disorders". Journal of Medicinal Chemistry. 58 (23): 9154–70. doi:10.1021/acs.jmedchem.5b00928. PMID 26509640.
^ Van der Kam E, Turner S, van Bergeij J, Mueller R, Mezler M, Bespalov A, Hobson A, Harris CM, Rendenbach-Mueller B, Schoemaker H (Jun 2014). "The use of selective sphingosine-1-phosphate receptor 5 agonists for the treatment of neurodegenerative disorders such as alzheimer's disease and lysosomal storage diseases such as niemann-pick c disease". Alzheimer's & Dementia. 10 (4): P281. doi:10.1016/j.jalz.2014.07.153.
^ Di Pardo A, Castaldo S, Amico E, Pepe G, Marracino F, Capocci L, Giovannelli A, Madonna M, van Bergeijk J, Buttari F, van der Kam E, Maglione V (Apr 2018). "Stimulation of S1PR5 with A-971432, a selective agonist, preserves blood-brain barrier integrity and exerts therapeutic effect in an animal model of Huntington's disease". Human Molecular Genetics. 27 (14): 2490–2501. doi:10.1093/hmg/ddy153. PMID 29688337.