Medicinal Chemistry Research Center, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
Bioorg Med Chem Lett. 2010 Feb 1;20(3):922-6. doi: 10.1016/j.bmcl.2009.12.070. Epub 2009 Dec 23.
Described herein is design, synthesis, and biological evaluation of novel series of 2-aryl-7-(3',4'-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines acting as inhibitors of type 4 phosphodiesterase (PDE4) which is known as a good target for the treatment of asthma and COPD. For this purpose, structure optimization was conducted with the aid of structure-based drug design using the known X-ray crystallography. Also, biological effects of these compounds on the target enzyme were evaluated by using in vitro assays, leading to the potent and selective PDE-4 inhibitor (IC(50)<10nM).
本文描述了新型 2-芳基-7-(3',4'- 二烷氧基苯基)-吡唑并[1,5-a]嘧啶类化合物的设计、合成和生物学评价，这些化合物作为磷酸二酯酶 4（PDE4）抑制剂，可用于治疗哮喘和 COPD 等疾病。为此，采用基于结构的药物设计方法，借助已知的 X 射线晶体学，进行了结构优化。此外，还通过体外测定法评估了这些化合物对靶酶的生物学效应，得到了高效且选择性的 PDE-4 抑制剂（IC50<10nM）。
