discovery of nivasorexant, an orexin-1 receptor antagonist

link to J. Med. Chem. article:

This video describes the discovery of nivasorexant, a selective orexin-1 receptor antagonists for the treatment of obsessive compulsive disorders. The content of this video was reported by scientists of Idorsia Pharmaceuticals in Allschwil, Switzerland as a Drug Annotation article in the Journal of Medicinal Chemistry. The discovery project started with an advanced compound from previous research, a dual orexin receptor antagonist with poor selectivity between OX1 and OX2. Selectivity for OX1 was refined through improved understanding of the SAR of the series. Research culminated in a compound that was orally available with good brain exposure and efficacy in a rat model for behavioral disorders. Nivasorexant completed phase I trials but failed to meet its primary endpoint in a phase II trial for eating disorders.

This video was created for academic purposes. The creator of the video has no financial stake in the sponsor of the research described in this video.

[kuyayan]

Fascinating! Randomly (and happily) suggested this video. I happen to regularly read NIH articles too. Subscribed!!

[AlistairKarim]

Got to this video randomly, simply from my recommended tab. And, actually, it's a hell of a lot interesting. Neurochemistry is alien tech to me, but I've dealt at one point with some disorder concerning the hypothalamus. I would easily bet that even if it's useless for eating disorders, simply having an effective orexin antagonist on the market will find its problem and its client. It's a rather rare receptor to target, only modafinil and derivatives come to mind.

[joshyu]

I don't remember ever seeing a drug with brain to plasma ratio greater than 1. If this is true, it's incredible.

[andywong]

Is there any possibility that you can introduce some prodrug design and synthesis work?