title: (3R)-3-amino-4-(2,4,5-trifluorophenyl)-N-{4-[6-(2-methoxyethoxy)benzothiazol-2-yl]tetrahydropyran-4-yl}butanamide as a potent dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.
abstract: Novel series of 3-amino-N-(4-aryl-1,1-dioxothian-4-yl)butanamides and 3-amino-N-(4-aryltetrahydropyran-4-yl)butanamides were synthesized and evaluated as dipeptidyl peptidase IV (DPP-IV) inhibitors. Derivatives incorporating the 6-substituted benzothiazole group showed highly potent DPP-IV inhibitory activity. Oral administration of (3R)-3-amino-4-(2,4,5-trifluorophenyl)-N-{4-[6-(2-methoxyethoxy)benzothiazol-2-yl]tetrahydropyran-4-yl}butanamide (12u) reduced blood glucose excursion in an oral glucose tolerance test.
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries Inc., 6-10-1, Tebiro, Kamakura, Kanagawa 248-8555, Japan. Aiko_Nitta@nts.toray.co.jp
authors.forename: Aiko
authors.initials: A
authors.lastname: Nitta
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sakami
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Ohyama
authors.forename: Mikiya
authors.initials: M
authors.lastname: Satoh
authors.forename: Junko
authors.initials: J
authors.lastname: Nakaki
authors.forename: Shiho
authors.initials: S
authors.lastname: Satoh
authors.forename: Chifumi
authors.initials: C
authors.lastname: Inada
authors.forename: Hideki
authors.initials: H
authors.lastname: Kozono
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kumagai
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shimamura
authors.forename: Tominaga
authors.initials: T
authors.lastname: Fukazawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Kawai
mesh_terms: D000284:Administration, Oral; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005746:Gastric Emptying; D052216:Glucagon-Like Peptide 1 / Q000737:chemistry; D005951:Glucose Tolerance Test; D006801:Humans; D020128:Inhibitory Concentration 50; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008956:Models, Chemical; D011714:Pyrans / Q000737:chemistry*
chemical_list: C540065:3-amino-4-(2,4,5-trifluorophenyl)-N-(4-(6-(2-methoxyethoxy)benzothiazol-2-yl)tetrahydropyran-4-yl)butanamide; D052160:Benzothiazoles; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004791:Enzyme Inhibitors; D011714:Pyrans; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4