Phosphodiesterase inhibitors. Part 2: Design, synthesis, and structure–activity relationships of dual PDE3/4-inhibitory pyrazolo[1,5-a]pyridines with anti-inflammatory and bronchodilatory activity

Autor:	Koji Ochiai, David R. Adams, Hitomi Zushi, Naoki Ando, Tokutaro Yasue, Kazuhiko Iwase, Akira Ohinata, Yasushi Kohno, Tetsuya Kishi, Kazunori Fukuchi
Rok vydání:	2011
Předmět:	Pyridines Stereochemistry medicine.drug_class Guinea Pigs Clinical Biochemistry Phosphodiesterase 3 Drug Evaluation Preclinical Pharmaceutical Science Ibudilast Pharmacology Phosphodiesterase 3 Inhibitors Inhibitory postsynaptic potential Biochemistry Anti-inflammatory Structure-Activity Relationship Drug Discovery medicine Animals Molecular Biology Roflumilast Therapeutic window Dose-Response Relationship Drug Molecular Structure Chemistry Anti-Inflammatory Agents Non-Steroidal Organic Chemistry Phosphodiesterase Stereoisomerism Cyclic Nucleotide Phosphodiesterases Type 3 Bronchodilator Agents Cyclic Nucleotide Phosphodiesterases Type 4 Rats Design synthesis Drug Design Pyrazoles Molecular Medicine Phosphodiesterase 4 Inhibitors medicine.drug
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 21:5451-5456
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2011.06.118
Popis:	A structural survey of pyrazolopyridine-pyridazinone phosphodiesterase (PDE) inhibitors was made with a view to optimization of their dual PDE3/4-inhibitory activity for respiratory disease applications. These studies identified (−)-6-(7-methoxy-2-trifluoromethylpyrazolo[1,5-a]pyridine-4-yl)-5-methyl-4,5-dihydro-3-(2H)-pyridazinone (KCA-1490, compound 2ac) as a compound with potent combined bronchodilatory and anti-inflammatory activity and an improved therapeutic window over roflumilast.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8e45d34f54d9955a24410feaa86d5169 https://doi.org/10.1016/j.bmcl.2011.06.118 Zobrazit plný text záznamu Full Text from ScienceDirect