选择性磷酸二酯酶4B（PDE4B）抑制剂的发现。
Discovery of selective PDE4B inhibitors.
作者信息
Naganuma Kenji, Omura Akifumi, Maekawara Naomi, Saitoh Masahiro, Ohkawa Naoto, Kubota Takashi, Nagumo Hiromitsu, Kodama Toshiyuki, Takemura Masayoshi, Ohtsuka Yuji, Nakamura Junji, Tsujita Ryuichi, Kawasaki Koh, Yokoi Hirotsugu, Kawanishi Masashi
机构信息
Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
出版信息
Bioorg Med Chem Lett. 2009 Jun 15;19(12):3174-6. doi: 10.1016/j.bmcl.2009.04.121. Epub 2009 May 3.
In this study the first PDE4B selective inhibitor is described. Optimization of lead 2-arylpyrimidine derivatives afforded a series of potent PDE4B inhibitors with >100-fold selectivity over the PDE4D isozyme. With a good pharmacokinetic profile, a selected compound exhibited potent anti-inflammatory effects in vivo and showed less emesis compared with Cilomilast.
在本研究中，描述了首个PDE4B选择性抑制剂。对先导化合物2-芳基嘧啶衍生物进行优化，得到了一系列对PDE4D同工酶具有大于100倍选择性的强效PDE4B抑制剂。一种选定的化合物具有良好的药代动力学特征，在体内表现出强效抗炎作用，且与西洛司特相比呕吐反应较少。
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