(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.
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.
Nitta
Aiko
A
Pharmaceutical Research Laboratories, Toray Industries Inc., 6-10-1, Tebiro, Kamakura, Kanagawa 248-8555, Japan. Aiko_Nitta@nts.toray.co.jp
Fujii
Hideaki
H
Sakami
Satoshi
S
Nishimura
Yutaka
Y
Ohyama
Tomofumi
T
Satoh
Mikiya
M
Nakaki
Junko
J
Satoh
Shiho
S
Inada
Chifumi
C
Kozono
Hideki
H
Kumagai
Hiroki
H
Shimamura
Masahiro
M
Fukazawa
Tominaga
T
Kawai
Hideki
H
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*
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