Premium
(1,3‐Diphenyl‐1 H ‐Pyrazol‐4‐yl)‐Methylamine Analogues as Inhibitors of Dipeptidyl Peptidases
Author(s) -
Hsu Tsu,
Chen ChiungTong,
Tsai TingYueh,
Cheng JaiHong,
Wu SuYing,
Chang ChungNien,
Chien ChiaHui,
Yeh KaiChia,
Huang YuWen,
Huang ChenLung,
Huang ChungYu,
Wu SsuHui,
Chiang YiKun,
Wang MinHsien,
Chao YuSheng,
Chen Xin,
Jiaang WeirTorn
Publication year - 2009
Publication title -
journal of the chinese chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.329
H-Index - 45
eISSN - 2192-6549
pISSN - 0009-4536
DOI - 10.1002/jccs.200900152
Subject(s) - chemistry , methylamine , methylamines , pyrazole , ring (chemistry) , stereochemistry , biochemistry , organic chemistry
A number of pyrazole compounds reported in literatures elicit anti‐hyperglycemic effects. By modifying the side chain of the heterocyclic skeleton, a new chemical class of DPP‐IV inhibitors structurally derived from the (pyrazol‐4‐yl)‐methylamine scaffold have been discovered and evaluated the biological activities of these inhibitors against DPP‐IV, DPP8, DPP‐II and FAP. The SAR studies showed the (1,3‐diphenyl‐1 H ‐pyrazol‐4‐yl)‐methylamines with 2,4‐dichloro substituents at the 3‐phenyl ring selectively preferred as DPP‐IV inhibitors, whereas with difluoro substituents at the 3‐phenyl ring selectively preferred as DPP8 inhibitors. The binding mode of representative compound 15h at the active site of DPP‐IV was predicted by computer model. In additional, 15h exhibited the ability to significantly decrease the glucose excursion in mice.