Design, synthesis, and biological evaluation of new phosphodiesterase type 4 inhibitors

The mode of interaction with enzyme is hypothesized based on the SAR data. The design, synthesis, and biological evaluation of new phosphodiesterase type 4 inhibitors, which possess new templates instead of a cyclohexane ring, are described. The mode of interaction with the enzyme is discussed based...

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Veröffentlicht in:Bioorganic & medicinal chemistry 2004-10, Vol.12 (19), p.5063-5078
Hauptverfasser: Ochiai, Hiroshi, Odagaki, Yoshihiko, Ohtani, Tazumi, Ishida, Akiharu, Kusumi, Kensuke, Kishikawa, Katuya, Yamamoto, Susumu, Takeda, Hiroshi, Obata, Takaaki, Kobayashi, Kaoru, Nakai, Hisao, Toda, Masaaki
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Sprache:eng
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Zusammenfassung:The mode of interaction with enzyme is hypothesized based on the SAR data. The design, synthesis, and biological evaluation of new phosphodiesterase type 4 inhibitors, which possess new templates instead of a cyclohexane ring, are described. The mode of interaction with the enzyme is discussed based on the structure–activity relationship (SAR) data obtained for the synthesized inhibitors. Furthermore, the roles of three pharmacophores, a catechol moiety, a nitrile moiety, and acidic moieties, are discussed using in silico docking studies. More detailed biological evaluations of selected compounds are also presented.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2004.07.040