Synthesis of pyrimido[4,5-c]azepine- and pyrimido[4,5-c]oxepine-based γ-secretase modulators

Bioorg Med Chem Lett. 2016 Mar 15;26(6):1554-1557. doi: 10.1016/j.bmcl.2016.02.016. Epub 2016 Feb 8.

Abstract

This Letter describes an efficient ring-closing metathesis approach to 2-chloro-4-amino-pyrimido[4,5-c]azepines and 2-chloro-4-amino-pyrimido[4,5-c]oxepines. These chlorides were applied to the synthesis of several potent γ-secretase modulators (GSMs).

Keywords: 2-Chloro-pyrimido[4,5-c]azepin-4-amine; 2-Chloro-pyrimido[4,5-c]oxepin-4-amine; Ring-closing metathesis (RCM); γ-Secretase modulator (GSM).

MeSH terms

  • Amyloid Precursor Protein Secretases / metabolism*
  • Azepines / chemical synthesis
  • Azepines / chemistry
  • Azepines / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Oxepins / chemical synthesis
  • Oxepins / chemistry
  • Oxepins / pharmacology*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Azepines
  • Oxepins
  • Pyrimidines
  • Amyloid Precursor Protein Secretases