Optimization of the aminopyridopyrazinones class of PDE5 inhibitors: discovery of 3-[(trans-4-hydroxycyclohexyl)amino]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one

Autor:	Mike B. Tollefson, Joseph B. Moon, Brent V. Mischke, E. Jon Jacobsen, D. Joseph Rogier, Alan G. Benson, Maddux Todd Michael, Brad A. Acker, Jeanne M. Rumsey, John N. Freskos, Blevis-Bal Radhika M, Alan MacInnes, Yi Zheng, Steve E. Heasley, Brown David L, John K. Walker, Yvette M. Fobian, Dafydd R. Owen, Jerry W. Cubbage, Robert Hughes, Ying Yu, John M. Molyneaux, Brian R. Bond
Rok vydání:	2009
Předmět:	medicine.drug_mechanism_of_action Stereochemistry Phosphodiesterase Inhibitors Pyridines Clinical Biochemistry Pharmaceutical Science Biochemistry Chemical synthesis chemistry.chemical_compound Structure-Activity Relationship Dogs Rats Inbred SHR Drug Discovery medicine Structure–activity relationship Animals Humans Protein Isoforms Molecular Biology chemistry.chemical_classification Cyclic Nucleotide Phosphodiesterases Type 5 Cyclic Nucleotide Phosphodiesterases Type 6 biology Bicyclic molecule Chemistry Drug discovery Organic Chemistry Phosphodiesterase 5 Inhibitors Rats Enzyme Enzyme inhibitor Pyrazines biology.protein Lactam Molecular Medicine Phosphodiesterase 5 inhibitor
Zdroj:	Bioorganicmedicinal chemistry letters. 19(17)
ISSN:	1464-3405
Popis:	We describe efforts to improve the pharmacokinetic profile of the aminopyridopyrazinone class of PDE5 inhibitors. These efforts led to the discovery of 3-[(trans-4-hydroxycyclohexyl)amino]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, a potent and selective inhibitor of PDE5 with an excellent PK profile.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::56bba8721c0b4d57439e25992ba23e4b https://pubmed.ncbi.nlm.nih.gov/19631533 Zobrazit plný text záznamu Full Text from ScienceDirect