H3R antagonist 1 hydrochloride

• CAT Number: I046296
• CAS Number: 2319790-07-1
• Molecular Formula: C19H24ClN3O3
• Molecular Weight: 377.87
• Purity: ≥95%
• Synonyms: 3-(1,3-benzodioxol-5-yl)-5-[(1-cyclobutylpiperidin-4-yl)methyl]-1,2,4-oxadiazole;hydrochloride
• InChI: InChI=1S/C19H23N3O3.ClH/c1-2-15(3-1)22-8-6-13(7-9-22)10-18-20-19(21-25-18)14-4-5-16-17(11-14)24-12-23-16;/h4-5,11,13,15H,1-3,6-10,12H2;1H
• InChIKey: AUFJPTAYJFKWNF-UHFFFAOYSA-N
• SMILES: C1CC(C1)N2CCC(CC2)CC3=NC(=NO3)C4=CC5=C(C=C4)OCO5.Cl

H3R antagonist 1 hydrochloride is a histamine receptor 3 (H3R) inverse agonist extracted from patent WO2013107336A1, compound example 2.
Treatment with H3R antagonist 1 hydrochloride, which is a H3R inverse agonist, promotes oligodendrocyte precursor cell (OPC) differentiation in a dose-dependent manner, at EC50=25 nM. Western blot reveals a significant increase in expression levels of two markers of mature oligodendrocytes, myelin-associated glycoprotein (MAG) and myeline basic protein (MBP) in differentiating oligodendrocytes after treatment with H3R antagonist 1 hydrochloride, which suggests that treatment with H3R antagonist 1 hydrochloride drives more OPCs to differentiate. H3R antagonist 1 hydrochloride increases the Forskolin-stimulated cAMP level in the primary oligodendrocyte precursor cells in a dose-dependent manner[1].
The ability of H3R antagonist 1 hydrochloride-1 to enhance in vivo remyelination is determined with the Cuprizone/Rapamycin-induced demyelination model. Mice are treated with Cuprizone diet combined with intraperitoneal injections of Rapamycin for 5 weeks followed by 9 days of compound administration. Cuprizone diet plus intraperitoneal injections of Rapamycin induced severe demyelination in both corpus callosum and cortex and treatment with H3R antagonist 1 hydrochloride (30 mg/kg, 9 days) significantly increases density of myelin specific Black-gold II staining in the lesion of corpus callosum and cortex in forebrain, compared to vehicle control group[1].

Reference

[1]. WANG, Rong, et al. THERAPEUTIC USES. WO2013107336A1.