title: Synthesis, structure-activity relationship studies, and identification of novel 5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine derivatives as dual orexin receptor antagonists. Part 1.
abstract: A novel series of non-peptidic OX1R/OX2R orexin receptor antagonists was prepared by heterocyclic replacement of the dimethoxyphenyl moiety contained in the tetrahydroisoquinoline core skeleton of almorexant. Introduction of substituted imidazole moieties delivered potent dual orexin receptor antagonists with nanomolar potency for hOX1R and hOX2R suitable for further fine-tuning. The preparation of these novel orexin receptor antagonists and the outcome of preliminary structure-activity relationship studies are described in this communication.
authors: Actelion Pharmaceuticals Ltd, Drug Discovery and Preclinical Research & Development, Gewerbestrasse 16, CH-4123 Allschwil, Switzerland.
authors: Thierry
authors: T
authors: Sifferlen
authors: Ralf
authors: R
authors: Koberstein
authors: Emmanuelle
authors: E
authors: Cottreel
authors: Amandine
authors: A
authors: Boller
authors: Thomas
authors: T
authors: Weller
authors: John
authors: J
authors: Gatfield
authors: Catherine
authors: C
authors: Brisbare-Roch
authors: Francois
authors: F
authors: Jenck
authors: Christoph
authors: C
authors: Boss
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D064446:Orexin Receptors; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: C578626:HCRTR2 protein, human; D064446:Orexin Receptors; D011719:Pyrazines; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide