Title of article :
Synthesis, biological evaluation, and metabolic stability of acrylamide derivatives as novel CCR3 antagonists Original Research Article
Author/Authors :
Ippei Sato، نويسنده , , Koichiro Morihira، نويسنده , , Hiroshi Inami، نويسنده , , Hirokazu Kubota، نويسنده , , Tatsuaki Morokata، نويسنده , , Keiko Suzuki، نويسنده , , Kazuki Ohno، نويسنده , , Yosuke Iura، نويسنده , , Aiko Nitta، نويسنده , , Takayuki Imaoka، نويسنده , , Toshiya Takahashi، نويسنده , , Makoto Takeuchi، نويسنده , , Mitsuaki Ohta، نويسنده , , Shin-ichi Tsukamoto، نويسنده ,
Abstract :
Our laboratory has identified several acrylamide derivatives with potent CCR3 inhibitory activity. In the present study, we evaluated the in vitro metabolic stability (CLint; mL/min/kg) of these compounds in human liver microsomes (HLMs), and assessed the relationship between their structures and CLint values. Among the compounds identified, N-{(3R)-1-[(6-fluoro-2-naphthyl)methyl]pyrrolidin-3-yl}-2-[1-(2-hydroxybenzoyl)piperidin-4-ylidene]acetamide (30j) was found to be a potent inhibitor (IC50 = 8.4 nM) with a high metabolic stability against HLMs.
Keywords :
Acrylamide derivatives , Allergic diseases , Clint , CCR3 antagonists
