title: Tetrahydroquinoline-based tricyclic amines as potent and selective agonists of the 5-HT2Creceptor.
abstract: The syntheses, structure-activity relationships (SARs), and biological activities of tetrahydroquinoline-based tricyclic amines as 5-HT2Creceptor agonists are reported. An early lead containing a highly unique 6,6,7-ring system was optimized for both in vitro potency and selectivity at the related 5-HT2Breceptor. Orally bioactive, potent, and selective 6,6,6-tricyclic 5-HT2Cagonists were identified.
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA. Electronic address: tschrader619@gmail.com.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Schrader
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Kasem
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Ren
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Konrad
authors.initials: K
authors.lastname: Feichtinger
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Bilal
authors.initials: B
authors.lastname: Al Doori
authors.affiliation: WuXi AppTec (Wuhan) Co Ltd., 666 Gaoxin Road, East Lake High-tech Development Zone, Wuhan 430075, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wei
authors.affiliation: WuXi AppTec (Wuhan) Co Ltd., 666 Gaoxin Road, East Lake High-tech Development Zone, Wuhan 430075, China.
authors.forename: Chunrui
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Huong
authors.initials: H
authors.lastname: Dang
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Minh
authors.initials: M
authors.lastname: Le
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Gatlin
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Kelli
authors.initials: K
authors.lastname: Chase
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Whelan
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Carleton
authors.initials: C
authors.lastname: Sage
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Grottick
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Graeme
authors.initials: G
authors.lastname: Semple
mesh_terms: D000284:Administration, Oral; D000588:Amines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D015394:Molecular Structure; D011804:Quinolines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D011804:Quinolines; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; C542964:1,2,3,4-tetrahydroquinoline
keywords: 5-HT(2C) agonists; CNS drugs; Lorcaserin; Tetrahydroquinoline; Tricyclic amines