title: Identification of MK-1925: a selective, orally active and brain-penetrable opioid receptor-like 1 (ORL1) antagonist.
abstract: Structure-activity relationship studies directed toward improving the metabolic stability of compound 1 resulted in the identification of 3-[5-(3,5-difluorophenyl)-3-({[(1S,3R)-3-fluorocyclopentyl]amino}methyl)-4-methyl-1H-pyrazol-1-yl]propanenitrile 39 (MK-1925) as a selective, orally available and brain-penetrable opioid receptor-like 1 (ORL1) antagonist. The compound also showed in vivo efficacy after oral dosing. Therefore, compound 39 was selected to undergo further studies as a clinical candidate.
authors: Tsukuba Research Institute, Banyu Pharmaceutical Co, Ltd, Okubo-3, Tsukuba, Ibaraki 300-2611, Japan.
authors: Kensuke
authors: K
authors: Kobayashi
authors: Tomohiro
authors: T
authors: Tsujita
authors: Hirokatsu
authors: H
authors: Ito
authors: Satoshi
authors: S
authors: Ozaki
authors: Takeshi
authors: T
authors: Tani
authors: Yasuyuki
authors: Y
authors: Ishii
authors: Shoki
authors: S
authors: Okuda
authors: Kiyoshi
authors: K
authors: Tadano
authors: Takahiro
authors: T
authors: Fukuroda
authors: Hisashi
authors: H
authors: Ohta
authors: Osamu
authors: O
authors: Okamoto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009292:Narcotic Antagonists; D009570:Nitriles / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D011720:Pyrazoles / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
chemical_list: C543967:3-(5-(3,5-difluorophenyl)-3-((((1S,3R)-3-fluorocyclopentyl)amino)methyl)-4-methyl-1H-pyrazol-1-yl)propanenitrile; D009292:Narcotic Antagonists; D009570:Nitriles; D011720:Pyrazoles; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor