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Design, synthesis, and evaluation of 2-aryl-7-(3',4'-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel PDE-4 inhibitors. 2010

Ikyon Kim, and Jong Hwan Song, and Chang Min Park, and Joon Won Jeong, and Hyung Rae Kim, and Jin Ryul Ha, and Zaesung No, and Young-Lan Hyun, and Young Sik Cho, and Nam Sook Kang, and Dong Ju Jeon
Medicinal Chemistry Research Center, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.

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).

UI MeSH Term Description Entries
D010726 Phosphodiesterase Inhibitors Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases. Phosphodiesterase Antagonists,Phosphodiesterase Inhibitor,Phosphoric Diester Hydrolase Inhibitors,Antiphosphodiesterases,Inhibitor, Phosphodiesterase
D011720 Pyrazoles Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D004353 Drug Evaluation, Preclinical Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D054703 Cyclic Nucleotide Phosphodiesterases, Type 4 A cyclic nucleotide phosphodiesterase subfamily that is found predominantly in inflammatory cells and may play a role in the regulation of CELL-MEDIATED IMMUNITY. The enzyme family includes over twenty different variants that occur due to multiple ALTERNATIVE SPLICING of the mRNA of at least four different genes. Cyclic Nucleotide Phosphodiesterase PDE4 Family,Cyclic Nucleotide Phosphodiesterases, Type 4A,Cyclic Nucleotide Phosphodiesterases, Type 4A5,Cyclic Nucleotide Phosphodiesterases, Type 4B,Cyclic Nucleotide Phosphodiesterases, Type 4C,Cyclic Nucleotide Phosphodiesterases, Type 4D,Cyclic Nucleotide Phosphodiesterases, Type 4D3,PDE4 Phosphodiesterases,PDE4D3 Phosphodiesterase,Phosphodiesterase 4,Phosphodiesterase 4A,Phosphodiesterase 4B,Phosphodiesterase 4C,Phosphodiesterase 4D,Phosphodiesterase IV,Phosphodiesterase-4,Type 4 Cyclic Nucleotide Phosphodiesterase,cAMP-Specific Phosphodiesterase 4A5,Phosphodiesterase 4A5, cAMP-Specific,Phosphodiesterase, PDE4D3,Phosphodiesterases, PDE4,cAMP Specific Phosphodiesterase 4A5
D058988 Phosphodiesterase 4 Inhibitors Compounds that specifically inhibit PHOSPHODIESTERASE 4. PDE-4 Inhibitor,PDE4 Inhibitor,Phosphodiesterase 4 Inhibitor,Phosphodiesterase Type 4 Inhibitor,PDE-4 Inhibitors,PDE4 Inhibitors,Phosphodiesterase Type 4 Inhibitors,4 Inhibitor, Phosphodiesterase,Inhibitor, PDE-4,Inhibitor, PDE4,Inhibitor, Phosphodiesterase 4,Inhibitors, PDE-4,Inhibitors, PDE4,Inhibitors, Phosphodiesterase 4,PDE 4 Inhibitor,PDE 4 Inhibitors

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