Design, synthesis, and evaluation of 2-aryl-7-(3 ',4 '-dialkoxyphenyl)-pyrazolo [1,5-a]pyrimidines as novel PDE-4 inhibitors

作者：Kim Ikyon; Song Jong Hwan; Park Chang Min; Jeong Joon Won; Kim Hyung Rae; Ha Jin Ryul; No Zaesung; Hyun Young Lan; Cho Young Sik; Kang Nam Sook^*; Jeon Dong Ju

来源：Bioorganic & Medicinal Chemistry Letters, 2010, 20(3): 922-926.

DOI：10.1016/j.bmcl.2009.12.070

• PDE-4 inhibitor
• SBDD
• COPD
• Asthma

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) < 10 nM).

• 出版日期2010-2-1