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Synthetic studies on selective type 4 phosphodiesterase (PDE 4) inhibitors. 1. Structure-activity relationships and pharmacological evaluation of 1,8-naphthyridin-2(1H)-one derivatives. 2002

Kazuhisa Takayama, and Masahiro Iwata, and Hiroyuki Hisamichi, and Yoshinori Okamoto, and Motonori Aoki, and Akira Niwa
Institute for Drug Discovery Reserch, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan. takaya_k@yamanouchi.co.jp

In order to develop novel and orally active phosphodiesterase (PDE) 4 inhibitors, random screening was performed using our chemical library to find YM-10335 possessing the 1,8-naphthyridin-2(1H)-one skeleton which is a completely different structure from rolipram. In this report, the syntheses and structure-activity relationships of the YM-10335 derivatives were described. Some compounds showed selective inhibitory activities for PDE 4 derived from human peripheral blood cells and no effect on the other PDE types (1, 2, 3, 5). The inhibition of the tumor necrosis factor-alpha (TNF-alpha) release in vitro and the carrageenan-induced pleurisy in rats were also described.

UI MeSH Term Description Entries
D008297 Male Males
D009287 Naphthyridines A group of two-ring heterocyclic compounds consisting of a NAPHTHALENES double ring in which two carbon atoms, one per each ring, are replaced with nitrogens.
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
D010998 Pleurisy INFLAMMATION of PLEURA, the lining of the LUNG. When PARIETAL PLEURA is involved, there is pleuritic CHEST PAIN. Pleuritis,Pleurisies,Pleuritides
D002351 Carrageenan A water-soluble extractive mixture of sulfated polysaccharides from RED ALGAE. Chief sources are the Irish moss CHONDRUS CRISPUS (Carrageen), and Gigartina stellata. It is used as a stabilizer, for suspending COCOA in chocolate manufacture, and to clarify BEVERAGES. Carrageenin,iota-Carrageenan,kappa-Carrageenan,lambda-Carrageenan,iota Carrageenan,kappa Carrageenan,lambda Carrageenan
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
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015105 3',5'-Cyclic-AMP Phosphodiesterases Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP. 3',5'-Cyclic AMP 5'-Nucleotidohydrolase,3',5'-Cyclic-Nucleotide Phosphodiesterase,CAMP Phosphodiesterase,3',5' Cyclic AMP Phosphodiesterase,3',5'-Cyclic AMP Phosphodiesterase,3',5'-Cyclic Nucleotide Phosphodiesterase,3',5'-Cyclic-AMP Phosphodiesterase,3',5'-Nucleotide Phosphodiesterase,3,5-Cyclic AMP 5-Nucleotidohydrolase,3,5-Cyclic AMP Phosphodiesterase,3',5' Cyclic AMP 5' Nucleotidohydrolase,3',5' Cyclic AMP Phosphodiesterases,3',5' Cyclic Nucleotide Phosphodiesterase,3',5' Nucleotide Phosphodiesterase,3,5 Cyclic AMP 5 Nucleotidohydrolase,3,5 Cyclic AMP Phosphodiesterase,5'-Nucleotidohydrolase, 3',5'-Cyclic AMP,5-Nucleotidohydrolase, 3,5-Cyclic AMP,AMP 5'-Nucleotidohydrolase, 3',5'-Cyclic,AMP 5-Nucleotidohydrolase, 3,5-Cyclic,AMP Phosphodiesterase, 3',5'-Cyclic,AMP Phosphodiesterase, 3,5-Cyclic,Nucleotide Phosphodiesterase, 3',5'-Cyclic,Phosphodiesterase, 3',5'-Cyclic AMP,Phosphodiesterase, 3',5'-Cyclic Nucleotide,Phosphodiesterase, 3',5'-Cyclic-AMP,Phosphodiesterase, 3',5'-Cyclic-Nucleotide,Phosphodiesterase, 3',5'-Nucleotide,Phosphodiesterase, 3,5-Cyclic AMP,Phosphodiesterase, CAMP,Phosphodiesterases, 3',5'-Cyclic-AMP

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