title: Novel 4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)methylbenzofuran derivatives as selective alpha(2C)-adrenergic receptor antagonists.
abstract: The synthesis of a series of 4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)methyl-2-arylbenzofuran and 4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)methylbenzofuran-2-carboxamide derivatives as novel alpha(2C)-adrenergic receptor antagonists are described. Their affinity at three different human alpha(2)-adrenergic receptors is reported, and some of these compounds exhibited high affinity for the alpha(2C)-adrenergic receptor with high subtype selectivity. Among them, compound 10e has been found to show the anti-L-dopa-induced dyskinetic activity in marmosets. The structure-activity relationship of these compounds is also discussed.
authors.affiliation: Pharmaceutical Research Center, Kyowa Hakko Kogyo Co. Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan. koji.hagihara@kyowa.co.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Hagihara
authors.forename: Hajime
authors.initials: H
authors.lastname: Kashima
authors.forename: Kyoichiro
authors.initials: K
authors.lastname: Iida
authors.forename: Junichi
authors.initials: J
authors.lastname: Enokizono
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Uchida
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nonaka
authors.forename: Masako
authors.initials: M
authors.lastname: Kurokawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Shimada
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology*; D002144:Callithrix; D015259:Dopamine Agents / Q000494:pharmacology; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology; D006801:Humans; D007202:Indicators and Reagents; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D007980:Levodopa / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2; D013329:Structure-Activity Relationship
chemical_list: C519724:4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)methylbenzofuran; C547774:ADRA2C protein, human; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D001572:Benzofurans; D015259:Dopamine Agents; D007202:Indicators and Reagents; D007546:Isoquinolines; D018341:Receptors, Adrenergic, alpha-2; D007980:Levodopa