In this section, you can access to the latest technical information related to the FUTURE project topic.

Design and synthesis of furyl/thineyl pyrroloquinolones based on natural alkaloid perlolyrine, lead to the discovery of potent and selective PDE5 inhibitors

Based on perlolyrine (1), a natural alkaloid with weak PDE5 potency from the traditional Chinese aphrodisiac plant Tribulus terrestris L., a series ?-substituted tetrahydro-?-carboline (TH?C) derivatives were synthesized via T+BF4--mediated oxidative C–H functionalization of N-aryl TH?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.

» Author: Hongbo Zheng, Lin Li, Bin Sun, Yun Gao, Wei Song, Xiaoyu Zhao, Yanhui Gao, Zhiyu Xie, Nianzhao Zhang, Jianbo Ji, Huiqing Yuan, Hongxiang Lou

» Reference: European Journal of Medicinal Chemistry, Volume 150

» Publication Date: 25/04/2018

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