SB-334867

• CAT Number: I002847
• CAS Number: 249889-64-3
• Molecular Formula: C17H14ClN5O2
• Molecular Weight: 355.78
• Purity: ≥95%
• Synonyms: 1-(2-methyl-1,3-benzoxazol-6-yl)-3-(1,5-naphthyridin-4-yl)urea;hydrochloride
• InChI: InChI=1S/C17H13N5O2.ClH/c1-10-20-12-5-4-11(9-15(12)24-10)21-17(23)22-14-6-8-18-13-3-2-7-19-16(13)14;/h2-9H,1H3,(H2,18,21,22,23);1H
• InChIKey: BKZHSJNLPPAJKB-UHFFFAOYSA-N
• SMILES: CC1=NC2=C(O1)C=C(C=C2)NC(=O)NC3=C4C(=NC=C3)C=CC=N4.Cl

SB-334867 (SB 334867A) is an excellent,selective and blood–brain barrier permeable orexin-1 (OX1) receptor antagonist, shows selectivity over OX2 (pKb=7.4), 100-fold over 5-HT2B, 5-HT2C with pKi values of 5.4 and 5.3, respectively[1]. SB-334867 reduces ethanol consumption and inhibits the acquisition of morphine-induced sensitization to locomotor activity in vivo[2][3].
SB-334867 (100 pM– 10 μM) inhibits the orexin-A (10 nM) and orexin-B (100 nM)-induced calcium responses in a concentration-dependent manner, with apparent pKb values of 7.27±0.04 and 7.23±0.03, but has no effect on the calcium response elicited by UTP (3 μM), which activates an endogenous purinergic receptor in CHO-OX1 and CHO-OX2 cells[4].
SB-334867 (intraperitoneal injection; 20 mg/kg; 20 days) administers 15 min before morphine injection can significantly decrease the effect of the morphine challenge dose in mice in comparison with the sporadically morphine-treated group[2].SB334867 (intraperitoneal injection; 3, 10 and 30 mg/kg) significantly reduces ethanol intake relative to vehicle and does not effect water consumption in female P rats[3].SB334867 (intraperitoneal injection; 3, 10 and 30 mg/kg) reduces ethanol consumption at the 30 mg/kg dose, high dose suppresses sucrose intake relative to vehicle, and it results in lower blood ethanol concentrations (BECs) relative to both the 10 and 30 mg/kg doses[3].

Reference

[1]. Porter RA, et al. 1,3-Biarylureas as selective non-peptide antagonists of the orexin-1 receptor.Bioorg Med Chem Lett. 2001 Jul 23;11(14):1907-10.
 [Content Brief]

[2]. Łupina M, et al. SB-334867 (an Orexin-1 Receptor Antagonist) Effects on Morphine-Induced Sensitization in Mice-a View on Receptor Mechanisms.
 [Content Brief]

[3]. Anderson RI, et al. Orexin-1 and orexin-2 receptor antagonists reduce ethanol self-administration in high-drinking rodent models.Front Neurosci. 2014 Feb 25;8:33.
 [Content Brief]

[4]. Smart D, et al. SB-334867-A: the first selective orexin-1 receptor antagonist.Br J Pharmacol. 2001 Mar;132(6):1179-82.
 [Content Brief]