title: Discovery of furan-2-carbohydrazides as orally active glucagon receptor antagonists.
abstract: Furan-2-carbohydrazides were found as orally active glucagon receptor antagonists. Starting from the hit compound 5, we successfully determined the structure activity relationships of a series of derivatives obtained by modifying the acidity of the phenol. We identified the ortho-nitrophenol as a good scaffold for glucagon receptor inhibitory activity. Our efforts have led to the discovery of compound 7l as a potent glucagon receptor antagonist with good bioavailability and satisfactory long half-life.
authors.affiliation: Dainippon Sumitomo Pharma. Co. Ltd, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan. Electronic address: futoshi-hasegawa@ds-pharma.co.jp.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Hasegawa
authors.affiliation: Dainippon Sumitomo Pharma. Co. Ltd, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Niidome
authors.affiliation: Dainippon Sumitomo Pharma. Co. Ltd, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Migihashi
authors.affiliation: Dainippon Sumitomo Pharma. Co. Ltd, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Murata
authors.affiliation: Dainippon Sumitomo Pharma. Co. Ltd, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Negoro
authors.affiliation: Dainippon Sumitomo Pharma. Co. Ltd, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Dainippon Sumitomo Pharma. Co. Ltd, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Kato
authors.affiliation: Dainippon Sumitomo Pharma. Co. Ltd, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Fujii
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D051381:Rats; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D001549:Benzamides; D006834:Hydrazines; D018027:Receptors, Glucagon
keywords: Furan-2-carbohydrazide; Glucagon; Glucagon receptor antagonist; Hyperglucagonemia; Type 2 diabetes