title: Design, synthesis, and evaluation of 2-aryl-7-(3',4'-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel PDE-4 inhibitors.
abstract: 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).
authors.affiliation: Medicinal Chemistry Research Center, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
authors.forename: Ikyon
authors.initials: I
authors.lastname: Kim
authors.forename: Jong Hwan
authors.initials: JH
authors.lastname: Song
authors.forename: Chang Min
authors.initials: CM
authors.lastname: Park
authors.forename: Joon Won
authors.initials: JW
authors.lastname: Jeong
authors.forename: Hyung Rae
authors.initials: HR
authors.lastname: Kim
authors.forename: Jin Ryul
authors.initials: JR
authors.lastname: Ha
authors.forename: Zaesung
authors.initials: Z
authors.lastname: No
authors.forename: Young-Lan
authors.initials: YL
authors.lastname: Hyun
authors.forename: Young Sik
authors.initials: YS
authors.lastname: Cho
authors.forename: Nam
authors.initials: N
authors.lastname: Sook Kang
authors.forename: Dong Ju
authors.initials: DJ
authors.lastname: Jeon
mesh_terms: 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
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4