Nonracemic synthesis of GK-GKRP disruptor AMG-3969

J Org Chem. 2014 Apr 18;79(8):3684-7. doi: 10.1021/jo500336e. Epub 2014 Apr 10.

Abstract

A nonracemic synthesis of the glucokinase-glucokinase regulatory protein disruptor AMG-3969 (5) is reported. Key features of the synthetic approach are an asymmetric synthesis of the 2-alkynyl piperazine core via a base-promoted isomerization and a revised approach to the synthesis of the aminopyridinesulfonamide with an improved safety profile.

MeSH terms

  • Benzyl Compounds / chemical synthesis*
  • Benzyl Compounds / chemistry
  • Carbamates / chemical synthesis*
  • Carbamates / chemistry
  • Carrier Proteins / antagonists & inhibitors*
  • Carrier Proteins / chemistry
  • Indicators and Reagents / chemistry
  • Isomerism
  • Molecular Structure
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry

Substances

  • 1-benzyl-3-(1-propyn-1-yl)piperazine
  • 1-benzyl-3-(2-propyn-1-yl)-2,5-piperazinedione
  • 2-(4-(4-((6-amino-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol
  • Benzyl Compounds
  • Carbamates
  • Carrier Proteins
  • Indicators and Reagents
  • Piperazines
  • Pyridines
  • Sulfonamides
  • glucokinase regulatory protein
  • tert-butyl(5-(chlorosulfonyl)-2-pyridinyl)carbamate