IPSU是一种选择性，有口服活性和脑渗透性的OX2R拮抗剂，pKi值为7.85。
CAS：1373765-19-5
分子式：C23H27N5O2
分子量：405.49
纯度：98%
存储：Store at -20°C

Background:

IPSU is a selective, orally available and brain penetrant OX2R antagonist with a pKi of 7.85.

Orexin receptor antagonists represent attractive targets for the development of drugs for the treatment of insomnia. IPSU binds rapidly and reaches equilibrium very quickly in binding and/or functional assays[2].

IPSU has low blood clearance, shows high maximal blood exposure and AUC after oral dosing. It exhibits an acceptable absolute oral bioavailability and a brain/blood concentration ratio that indicated favorable brain penetration. IPSU increases sleep when dosed during the mouse active phase (lights off); IPSU induces sleep primarily by increasing NREM sleep. IPSU shows a fast onset of action, with a clear increase in total sleep time during the first hour afterdosing. The effect lasts 4-5 h, after which time the total sleep time per hour is the same as on vehicle day [1].

[1]. Betschart C, et al. Identification of a novel series of orexin receptor antagonists with a distinct effect on sleeparchitecture for the treatment of insomnia. J Med Chem. 2013 Oct 10;56(19):7590-607. [2]. Callander GE, et al. Kinetic properties of "dual" orexin receptor antagonists at OX1R and OX2R orexin receptors. Front Neurosci. 2013 Dec 3;7:230. [3]. Hoyer D, et al. Distinct effects of IPSU and suvorexant on mouse sleep architecture.