2. Academic Validation
  3. Discovery of triazole aminopyrazines as a highly potent and selective series of PI3Kδ inhibitors

Discovery of triazole aminopyrazines as a highly potent and selective series of PI3Kδ inhibitors

  • Bioorg Med Chem Lett. 2017 Feb 1;27(3):679-687. doi: 10.1016/j.bmcl.2016.11.004.
Ina Terstiege 1,  Matthew Perry 2,  Jens Petersen 3,  Christian Tyrchan 2,  Tor Svensson 2,  Helena Lindmark 3,  Linda Öster 3
Affiliations

Affiliations

  • 1 Respiratory, Inflammation & Autoimmunity, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, 43183, Sweden. Electronic address: Ina.Terstiege@astrazeneca.com.
  • 2 Respiratory, Inflammation & Autoimmunity, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, 43183, Sweden.
  • 3 Discovery Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, 43183, Sweden.
PMID: 28017532 DOI: 10.1016/j.bmcl.2016.11.004
Abstract

A novel class of potent PI3Kδ inhibitors with >1000-fold selectivity against Other class I PI3K isoforms is described. Optimization of the substituents on a triazole aminopyrazine scaffold, emerging from an in-house PI3Kα program, turned moderately selective PI3Kδ compounds into highly potent and selective PI3Kδ inhibitors. These efforts resulted in a series of aminopyrazines with PI3Kδ IC50⩽1nM in the Enzyme assay, some of the most selective PI3Kδ inhibitors published to date, with a cell potency in a JeKo-cell assay of 20-120nM.

Keywords

Aminopyrazine; Inflammation; PI3Kδ inhibitor; Phosphoinositide 3-kinase.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-122593
    99.62%, PI3Kδ Inhibitor