Design, synthesis, and evaluation of 2-aryl-7-(3',4'-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel PDE-4 inhibitors.
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).
Kim
Ikyon
I
Medicinal Chemistry Research Center, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
Song
Jong Hwan
JH
Park
Chang Min
CM
Jeong
Joon Won
JW
Kim
Hyung Rae
HR
Ha
Jin Ryul
JR
No
Zaesung
Z
Hyun
Young-Lan
YL
Cho
Young Sik
YS
Sook Kang
Nam
N
Jeon
Dong Ju
DJ
D000818:Animals; D018360:Crystallography, X-Ray; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D051379:Mice; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology
D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4