Literature DB >> 29752182

Discovery of a bicyclo[4.3.0]nonane derivative DS88790512 as a potent, selective, and orally bioavailable blocker of transient receptor potential canonical 6 (TRPC6).

Keisuke Motoyama1, Tsutomu Nagata2, Jun Kobayashi3, Akifumi Nakamura4, Naoki Miyoshi3, Miho Kazui5, Ken Sakurai6, Tomoko Sakakura6.   

Abstract

In this study, we aimed to synthesize a novel blocker of transient receptor potential canonical 6 (TRPC6). The sp2 carbon atoms of the aminoindane skeleton of the known inhibitor were replaced with sp3 carbon atoms to increase the molecular complexity, measured by fraction sp3 (Fsp3). The representative compound, a bicyclo[4.3.0]nonane derivative DS88790512, inhibited TRPC6 with an IC50 value of 11 nM. Notably, DS88790512 exhibited excellent selectivity against hERG and hNaV1.5 channels, and was identified as an orally bioavailable compound.
Copyright © 2018 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Bicyclic molecule; Fsp(3); Ion channel; Na(V)1.5; hERG

Mesh：

Substances：

Year:  2018        PMID： 29752182     DOI： 10.1016/j.bmcl.2018.03.056

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  7 in total

Review 1.  TRPC channels: Structure, function, regulation and recent advances in small molecular probes.

Authors:  Hongbo Wang; Xiaoding Cheng; Jinbin Tian; Yuling Xiao; Tian Tian; Fuchun Xu; Xuechuan Hong; Michael X Zhu
Journal:  Pharmacol Ther       Date:  2020-01-28       Impact factor: 12.310

2.  In vivo selective inhibition of TRPC6 by antagonist BI 749327 ameliorates fibrosis and dysfunction in cardiac and renal disease.

Authors:  Brian Leei Lin; Damian Matera; Julia F Doerner; Nan Zheng; Donato Del Camino; Sumita Mishra; Hong Bian; Svetlana Zeveleva; Xiaoguang Zhen; Nathaniel T Blair; Jayhong A Chong; David P Hessler; Djahida Bedja; Guangshuo Zhu; Grace K Muller; Mark J Ranek; Lynn Pantages; Mary McFarland; Matthew R Netherton; Angela Berry; Diane Wong; Georg Rast; Hu Sheng Qian; Steven M Weldon; Jay J Kuo; Achim Sauer; Chris Sarko; Magdalene M Moran; David A Kass; Steven S Pullen
Journal:  Proc Natl Acad Sci U S A       Date:  2019-04-26       Impact factor: 11.205

Review 3.  Canonical transient receptor potential channels and their modulators: biology, pharmacology and therapeutic potentials.

Authors:  Yuan-Yuan Gao; Wen Tian; Hui-Nan Zhang; Yang Sun; Jing-Ru Meng; Wei Cao; Xiao-Qiang Li
Journal:  Arch Pharm Res       Date:  2021-03-24       Impact factor: 4.946

Review 4.  Canonical Transient Receptor Potential (TRPC) Channels in Nociception and Pathological Pain.

Authors:  Zhi-Chuan Sun; Sui-Bin Ma; Wen-Guang Chu; Dong Jia; Ceng Luo
Journal:  Neural Plast       Date:  2020-03-21       Impact factor: 3.599

5.  Benzothiazole Amides as TRPC3/6 Inhibitors for Gastric Cancer Treatment.

Authors:  Yingjie Wei; Mengxian Zhang; Zhenbin Lyu; Guolin Yang; Tian Tian; Mingmin Ding; Xiaodong Zeng; Fuchun Xu; Pengyu Wang; Fangfang Li; Yixuan Liu; Zhengyu Cao; Jing Lu; Xuechuan Hong; Hongbo Wang
Journal:  ACS Omega       Date:  2021-03-24

6.  Schwarzinicine A inhibits transient receptor potential canonical channels and exhibits overt vasorelaxation effects.

Authors:  Yin-Ying Mak; Bi-Juin Loong; Paul Millns; Claudia C Bauer; Robin S Bon; Yvonne Mbaki; Fong-Kai Lee; Kuan-Hon Lim; Cin Kong; Sue-Mian Then; Kang-Nee Ting
Journal:  Phytother Res       Date:  2022-05-10       Impact factor: 6.388

Review 7.  Transient Receptor Potential Canonical (TRPC) Channels: Then and Now.

Authors:  Xingjuan Chen; Gagandeep Sooch; Isaac S Demaree; Fletcher A White; Alexander G Obukhov
Journal:  Cells       Date:  2020-08-28       Impact factor: 6.600
  7 in total

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