Bioorganic and Medicinal Chemistry Letters
Bioorganic and Medicinal Chemistry Letters
5 years ago

Substituted α-mercaptoketones, new types of specific neprilysin inhibitors

Substituted α-mercaptoketones, new types of specific neprilysin inhibitors
New neprilysin inhibitors containing an α-mercaptoketone HSC(R1R2)CO group, as zinc ligand were designed. Two parameters were explored for potency optimization: the size of the inhibitor which could interact with the S1, S1′ or S2′ domain of the enzyme and the nature of the substituents R1, R2 of the mercaptoketone group. Introduction of a cyclohexyl chain in R1, R2 position and a (3-thiophen)benzyl group in position R3 (compound 12n) yielded to the most potent inhibitor of this series with a Ki value of 2±0.3nM. This result suggests that this new inhibitor interacts within the S1, S1′ domain of NEP allowing a pentacoordination of the catalytic Zn2+ ion by the mercaptoketone moiety.

Publisher URL: www.sciencedirect.com/science

DOI: S0960894X17306479

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.