标题:Design and synthesis of furyl/thineyl pyrroloquinolones based on natural alkaloid perlolyrine, lead to the discovery of potent and selective PDE5 inhibitors
作者:Zheng, Hongbo; Li, Lin; Sun, Bin; Gao, Yun; Song, Wei; Zhao, Xiaoyu; Gao, Yanhui; Xie, Zhiyu; Zhang, Nianzhao; Ji, Jianbo; Yuan, H 更多
作者机构:[Zheng, Hongbo; Li, Lin; Sun, Bin; Gao, Yun; Song, Wei; Zhao, Xiaoyu; Gao, Yanhui; Xie, Zhiyu; Zhang, Nianzhao; Ji, Jianbo; Lou, Hongxiang] Shandong U 更多
通讯作者:Lou, HX
通讯作者地址:[Lou, HX]Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Key Lab Nat Prod & Chem Biol,Dept Nat Prod Chem, Jinan 250012, Shandong, Peoples R China.
来源:EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版年:2018
卷:150
页码:30-38
DOI:10.1016/j.ejmech.2018.02.039
关键词:PDE5 inhibitors; Pyrroloquinolones; Bioavailability; Male erectile; dysfunction (MED)
摘要:Based on perlolyrine (1), a natural alkaloid with weak PDE5 potency from the traditional Chinese aphrodisiac plant Tribulus terrestris L., a series alpha-substituted tetrahydro-beta-carboline (TH beta C) derivatives were synthesized via T(+)BF4(-)-mediated oxidative C-H functionalization of N-aryl TH beta Cs with diverse potassium trifluoroborates. Following Winterfeldt oxidation afforded the corresponding furyl/thienyl pyrroloquinolones, of which 5-ethylthiophene/ethylfuran derivatives 20a-b were identified as the most potent and selective PDE5 inhibitors. Among the enantiomers, (S)-20a and (S)-20b (IC50 = 0.52 and 0.39 nM) were found to be more effective than their (R)-antipode, display favorable pharmacokinetic profiles, exert in vitro vasorelaxant effects on the isolated thoracic aorta, and exhibit in vivo efficacy in the anesthetized rabbit erectile model. (C) 2018 Elsevier Masson SAS. All rights reserved.
收录类别:SCOPUS;SCIE
WOS核心被引频次:1
Scopus被引频次:1
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85042709806&doi=10.1016%2fj.ejmech.2018.02.039&partnerID=40&md5=c1e78192d36b38dd588183e4713ca072
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