Research Article | Volume: 4, Issue: 6, June, 2014

Exploring the Synthesis of New 1-(4-Substitutedphenylamino) imidazo[1,5-a]indol-3-one Derivatives as Cyclized Analogs of Leucettines

Guillaume Burgya b Emmanuelle Limantona François Carreauxa Emilie Durieub Laurent Meijerb and Jean-Pierre Bazureaua   

Open Access   

Published:  Jun 28, 2014

DOI: 10.7324/JAPS.2014.40604
Abstract

New 1-arylaminoimidazo[1,5-a]indol-3-ones were synthesized as cyclized derivatives of leucettine L41, a low molecular weight inhibitor of the DYRKs/CLKs protein kinases with potential applications in Alzheimer's disease and Down syndrome. In this first approach, access to the desired 1-aminoimidazo[1,5-a]indol-3-ones involved 5 steps and was explored with a series of various primary amines and polar secondary amines in order to introduce molecular diversity on N-1 position. The 5 step synthesis of the 1-arylaminoimidazo[1,5-a]indol-3-ones was achieved and the limiting step of this process was the final cyclization via a sulphur/nitrogen displacement from methylsulfanyl thiourea intermediates. Good results were obtained for isothioureas derived from primary amines. The 1-arylaminoimidazo[1,5-a]indol-3-ones were evaluated on a panel of five protein kinases (DYRK1A, CK1, CDK5/p25, GSK3α/β and CLK1).


Keyword:     Imidazo[15-A]Indol-3-One thiourea isothiorurea intramolecular sulphur/ nitrogen displacement protein kinase DYRKs CLKs Leucettines.


Citation:

Jean-Pierre BAZUREAU., Exploring the Synthesis of New 1-(4- Substitutedphenylamino) imidazo[1,5-a]indol-3-one Derivatives as Cyclized Analogs of Leucettines. J App Pharm Sci, 2014; 4 (06): 025-032.

Copyright:The Author(s). This is an open access article distributed under the Creative Commons Attribution Non-Commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HTML Full Text

Reference

Article Metrics
819 Views 40 Downloads 859 Total

Year

Month

Related Search

By author names

Citiaion Alert By Google Scholar

Name Required
Email Required Invalid Email Address

Comment required