Novel series of 3-amino-N-(4-aryl-1,1-dioxothian-4-yl)butanamides as potent and selective dipeptidyl peptidase IV inhibitors.
A series of novel 3-amino-N-(4-aryl-1,1-dioxothian-4-yl)butanamides were investigated as dipeptidyl peptidase IV (DPP-4) inhibitors. Introduction of a 4-phenylthiazol-2-yl group showed highly potent DPP-4 inhibitory activity. Among various derivatives, (3R)-3-amino-N-(4-(4-phenylthiazol-2-yl)-tetrahydro-2H-thiopyran-4-yl)-4-(2,4,5-trifluorophenyl)butanamide 1,1-dioxide (30) reduced blood glucose excursion in an oral glucose tolerance test by oral administration.
Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. aiko_nitta@nts.toray.co.jp
Aiko
A
Nitta
Hideaki
H
Fujii
Satoshi
S
Sakami
Mikiya
M
Satoh
Junko
J
Nakaki
Shiho
S
Satoh
Hiroki
H
Kumagai
Hideki
H
Kawai
D000284:Administration, Oral; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018938:Caco-2 Cells; D018819:Dipeptidyl Peptidase 4 / Q000097:blood / Q000737:chemistry* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D011485:Protein Binding; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
C579642:(3R)-3-amino-N-(4-(4-phenylthiazol-2-yl)-tetrahydro-2H-thiopyran-4-yl)-4-(2,4,5-trifluorophenyl)butanamide 1,1-dioxide; D000577:Amides; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D011714:Pyrans; D013844:Thiazoles; D018819:Dipeptidyl Peptidase 4