title: Phosphodiesterase inhibitors. Part 6: design, synthesis, and structure-activity relationships of PDE4-inhibitory pyrazolo[1,5-a]pyridines with anti-inflammatory activity.
abstract: We previously identified KCA-1490 [(-)-6-(7-methoxy-2-trifluoromethyl-pyrazolo[1,5-a]pyridin-4-yl)-5-methyl-4,5-dihydro-3-(2H)-pyridazinone], a dual PDE3/4 inhibitor. In the present study, we found highly potent selective PDE4 inhibitors derived from the structure of KCA-1490. Among them, N-(3,5-dichloropyridin-4-yl)-7-methoxy-2-(trifluoromethyl)pyrazolo[1,5-a]pyridine-4-carboxamide (2a) had good anti-inflammatory effects in an animal model.
authors.affiliation: Discovery Research Laboratories, Kyorin Pharmaceutical Co., Ltd., Nogi-machi, Shimotsuga-gun, Tochigi, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kojima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takita
authors.forename: Tatsunobu
authors.initials: T
authors.lastname: Sumiya
authors.forename: Koji
authors.initials: K
authors.lastname: Ochiai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Iwase
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kishi
authors.forename: Akira
authors.initials: A
authors.lastname: Ohinata
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yageta
authors.forename: Tokutaro
authors.initials: T
authors.lastname: Yasue
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kohno
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D020128:Inhibitory Concentration 50; D023421:Models, Animal; D015394:Molecular Structure; D058988:Phosphodiesterase 4 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D058988:Phosphodiesterase 4 Inhibitors; D011720:Pyrazoles; D011725:Pyridines
keywords: Anti-inflammatory; PDE4 inhibitor; Pyrazolo[1,5-a]pyridine; Pyridine