An atom economic synthesis and AChE inhibitory activity of novel dispiro 7-aryltetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole and 4-aryloctahydroindolizine N-methylpiperidin-4-one hybrid heterocycles

Eur J Med Chem. 2013 Jul:65:240-8. doi: 10.1016/j.ejmech.2013.04.050. Epub 2013 May 9.

Abstract

The 1,3-dipolar cycloaddition of azomethine ylides generated in situ from acenaphthenequinone and α-amino acids viz. 1,3-thiazolone-4-carboxylic acid and piperidine-2-carboxylic acid to a series of 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones afforded novel spiro[5.2″]acenaphthene-1″-onespiro[6.3']-5'-arylmethylidene-1'-methylpiperidin-4'-one-7-aryltetrahydro-1H-pyrrolo[1,2-c][1,3]thiazoles and spiro[2.2″]acenaphthene-1″-onespiro[3.3']-5'-arylmethylidene-1'-methylpiperidin-4'-one-4-aryloctahydroindolizines respectively in quantitative yields. These compounds were evaluated for their AChE inhibitory activity and compound 3c was found to be the most potent with IC50 1.86 μmol/L.

Keywords: 1,3-Dipolar cycloaddition; 1H-pyrrolo[1,2-c][1,3]thiazole; AChE inhibition; Azomethine ylide; Spiro-heterocycles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Electrophorus
  • Models, Molecular
  • Molecular Structure
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • Cholinesterase Inhibitors
  • Piperidines
  • Pyrroles
  • Thiazoles
  • pyrrolo(1,2-c)(1,3)thiazole
  • Acetylcholinesterase