[1,2,5]Oxadiazolo[3,4-b]pyrazine-5,6-diamine Derivatives as Mitochondrial Uncouplers for the Potential Treatment of Nonalcoholic Steatohepatitis.

Clicks: 164
ID: 92796
2020
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #86 of 122 articles by views in Journal of medicinal chemistry

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 122 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Small molecule mitochondrial uncouplers are emerging as a new class of molecules for the treatment of nonalcoholic steatohepatitis. We utilized BAM15, a potent protonophore that uncouples the mitochondria without depolarizing the plasma membrane, as a lead compound for structure-activity profiling. Using oxygen consumption rate as an assay for determining uncoupling activity, changes on the 5- and 6-position of the oxadiazolopyrazine core were introduced. Our studies suggest that unsymmetrical aniline derivatives bearing electron withdrawing groups are preferred compared to the symmetrical counterparts. In addition, alkyl substituents are not tolerated, and the N-H proton of the aniline ring is responsible for the protonophore activity. In particular, compound 10b had an EC50 value of 190 nM in L6 myoblast cells. In an in vivo model of NASH, 10b decreased liver triglyceride levels and showed improvement in fibrosis, inflammation, and plasma ALT. Taken together, our studies indicate that mitochondrial uncouplers have potential for the treatment of NASH.
Reference Key
childress2020125oxadiazolo34bpyrazine56diaminejournal Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Childress, Elizabeth S;Salamoun, Joseph;Hargett, Stefan;Alexopoulos, Stephanie;Chen, Sing-Young;Shah, Divya P;Santiago-Rivera, Jose;Garcia, Christopher;Dai, Yumin;Tucker, Simon P;Hoehn, Kyle;Santos, Webster L;
Journal Journal of medicinal chemistry
Year 2020
DOI
10.1021/acs.jmedchem.9b01440
URL
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.