title: Synthesis and evaluation of carbon-linked analogs of dual orexin receptor antagonist filorexant.
abstract: Analogs of the dual orexin receptor antagonist filorexant were prepared. Replacement of the ether linkage proved highly sensitive toward modification with an acetylene linkage providing compounds with the best in vitro and in vivo potency profiles.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. Electronic address: scott_d_kuduk@merck.com.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Kuduk
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Skudlarek
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Christina N
authors.initials: CN
authors.lastname: Di Marco
authors.affiliation: Department of In Vitro Pharmacology, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Bruno
authors.affiliation: Department of In Vitro Pharmacology, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Pausch
authors.affiliation: Department of In Vitro Pharmacology, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: O'Brien
authors.affiliation: Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Tamara D
authors.initials: TD
authors.lastname: Cabalu
authors.affiliation: Department of In Vivo Pharmacology, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Stevens
authors.affiliation: Department of In Vivo Pharmacology, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Brunner
authors.affiliation: Department of In Vivo Pharmacology, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Tannenbaum
authors.affiliation: Department of Neuroscience, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Gotter
authors.affiliation: Department of Neuroscience, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Winrow
authors.affiliation: Department of Neuroscience, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Renger
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Coleman
mesh_terms: D000114:Acetylene / Q000737:chemistry*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors / Q000172:deficiency / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C501103:Cd200r1 protein, mouse; C497459:Hcrtr1 protein, mouse; C573816:MK-6096; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D010880:Piperidines; D011743:Pyrimidines; D000114:Acetylene
keywords: Antagonist; Insomnia; Orexin