AChE inhibitor: a regio- and stereo-selective 1,3-dipolar cycloaddition for the synthesis of novel substituted 5,6-dimethoxy spiro[5.3']-oxindole-spiro-[6.3″]-2,3-dihydro-1H-inden-1″-one-7-(substituted aryl)-tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole

Mohamed Ashraf Ali; Rusli Ismail; Tan Soo Choon; Raju Suresh Kumar; Hasnah Osman; Natarajan Arumugam; Abdulrahman I Almansour; Karthikeyan Elumalai; Abhimanyu Singh

doi:10.1016/j.bmcl.2011.10.087

AChE inhibitor: a regio- and stereo-selective 1,3-dipolar cycloaddition for the synthesis of novel substituted 5,6-dimethoxy spiro[5.3']-oxindole-spiro-[6.3″]-2,3-dihydro-1H-inden-1″-one-7-(substituted aryl)-tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole

Bioorg Med Chem Lett. 2012 Jan 1;22(1):508-11. doi: 10.1016/j.bmcl.2011.10.087. Epub 2011 Nov 20.

Authors

Mohamed Ashraf Ali¹, Rusli Ismail, Tan Soo Choon, Raju Suresh Kumar, Hasnah Osman, Natarajan Arumugam, Abdulrahman I Almansour, Karthikeyan Elumalai, Abhimanyu Singh

Affiliation

¹ Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia. asraf80med@rediffmail.com

PMID: 22142546
DOI: 10.1016/j.bmcl.2011.10.087

Abstract

Pyrrolothiazolyloxindole analogues share vital pharmacological properties, considered useful in Alzheimer's disease (AD). The aim of this study was synthesis and evaluate pyralothiazolyloxindole analogues if possess acetyl cholinesterase (AChE) inhibitory activity. The easily accessible one-pot synthesis of these compounds resulted to be significantly less difficult and expensive than that of donepezil. Several compounds possess anti-cholinesterase activity in the order of micro and sub-micromolar. Particularly, compound was the most potent inhibitors of the series against acetyl cholinesterase enzyme with IC(50) 0.11μmol/L.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase / chemistry*
Alzheimer Disease / drug therapy
Alzheimer Disease / metabolism
Azo Compounds / chemistry
Chemistry, Pharmaceutical / methods
Cholinesterase Inhibitors / chemical synthesis*
Cholinesterase Inhibitors / pharmacology*
Donepezil
Drug Design
Humans
Indans / pharmacology
Indoles / chemistry
Inhibitory Concentration 50
Magnetic Resonance Spectroscopy / methods
Models, Chemical
Models, Molecular
Molecular Conformation
Piperidines / pharmacology
Spiro Compounds / chemical synthesis*
Spiro Compounds / pharmacology
Structure-Activity Relationship
Temperature
Thiazoles / chemistry
Thiosemicarbazones / chemistry
Triazoles / chemical synthesis*
Triazoles / pharmacology

Substances

Azo Compounds
Cholinesterase Inhibitors
Indans
Indoles
Piperidines
Spiro Compounds
Thiazoles
Thiosemicarbazones
Triazoles
azomethine
Donepezil
Acetylcholinesterase