Synthesis,biological evaluation,and metabolic stability of acrylamide derivatives as novel CCR3 antagonists |
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| Authors: | Ippei Sato Koichiro Morihira Hiroshi Inami Hirokazu Kubota Tatsuaki Morokata Keiko Suzuki Kazuki Ohno Yosuke Iura Aiko Nitta Takayuki Imaoka Toshiya Takahashi Makoto Takeuchi Mitsuaki Ohta Shin-ichi Tsukamoto |
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| Affiliation: | 1. Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan;2. Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-0036, Japan |
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| 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. |
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