title: Substituted cyclopentanes, tetrahydrofurans and pyrrolidines as orexin-1-receptor antagonists for treatment of various CNS disorders (WO2015/055994; WO2015/124932; WO2015/124934).
abstract: The three patent applications WO2015/055994, WO2015/124932 and WO2015/124934 from Takeda Pharmaceuticals describe antagonists for the orexin-1 receptor, based on saturated substituted five-membered carbo- or heterocycles. According to the patent applications, the compounds have utility in therapeutic areas such as schizophrenia and other psychotic disorders, anxiety or addiction disorders, among others. The patent applications together describe almost 300 examples, and for most of them activity data, determined by Fluorescence Imaging Plate Reader (FLIPR) technology on the orexin-1 as well as the orexin-2 receptor, are disclosed. Structurally, the building blocks used to prepare the compounds are reminiscent of other orexin antagonist programs recently disclosed in the literature. However, the templates used are novel in the orexin antagonist field and are probably the key feature for the selectivity of the derivatives towards the orexin-1 receptor.
authors.affiliation: a Drug Discovery, Chemistry Technologies and Lead Discovery , Actelion Pharmaceuticals Ltd ., Allschwil , Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Boss
authors.affiliation: b Drug Discovery, CNS Pharmacology , Actelion Pharmaceuticals Ltd ., Allschwil , Switzerland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Roch
mesh_terms: D000818:Animals; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D003517:Cyclopentanes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D005663:Furans / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D000068796:Orexin Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D064446:Orexin Receptors / Q000187:drug effects* / Q000378:metabolism; D010330:Patents as Topic; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D003517:Cyclopentanes; D005663:Furans; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D011759:Pyrrolidines
keywords: G-protein coupled receptors (GPCR); Orexin-1-selective antagonists (1SORAs); Takeda Pharmaceutical Co; addiction; anxiety; schizophrenia