The synthesis and SAR of novel diarylsulfone 11β-HSD1 inhibitors

Autor:	Pingchen Fan, Dustin McMinn, Shichang Miao, Jinsong Liu, Ji Ma, Liang Tang, Xuelei Yan, Marc Labelle, Athena Sudom, Stefania Ursu, Michael DeGraffenreid, Yongmei Di, Xiao He, Zhulun Wang, Juan C. Jaen, Jay P. Powers, Daqing Sun, Hua Tu, Nigel Walker, Mario G. Cardozo, Qiuping Ye
Rok vydání:	2010
Předmět:	education Clinical Biochemistry Pharmaceutical Science Biochemistry Chemical synthesis Structure-Activity Relationship In vivo Drug Discovery 11-beta-Hydroxysteroid Dehydrogenase Type 1 Structure–activity relationship Animals Humans Pharmacokinetics Sulfones Enzyme Inhibitors Molecular Biology chemistry.chemical_classification biology Chemistry Organic Chemistry Biological activity humanities In vitro Enzyme Enzyme inhibitor biology.protein Molecular Medicine hormones hormone substitutes and hormone antagonists Ex vivo
Zdroj:	Bioorganicmedicinal chemistry letters. 20(23)
ISSN:	1464-3405
Popis:	In this communication, human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitory activities of a novel series of diarylsulfones are described. Optimization of this series resulted in several highly potent 11β-HSD1 inhibitors with excellent pharmacokinetic (PK) properties. Compound (S)-25 showed excellent efficacy in a non-human primate ex vivo pharmacodynamic model.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::daae63f2306af982135000129eb9d5f9 https://pubmed.ncbi.nlm.nih.gov/20971000 Zobrazit plný text záznamu Full Text from ScienceDirect