A-ring modifications on the triazafluorenone core structure and their mGluR1 antagonist properties

T K Sasikumar; Li Qiang; Duane A Burnett; William J Greenlee; Cheng Li; Mariagrazia Grilli; Rosalia Bertorelli; Gianluca Lozza; Angelo Reggiani

doi:10.1016/j.bmcl.2010.03.004

A-ring modifications on the triazafluorenone core structure and their mGluR1 antagonist properties

Bioorg Med Chem Lett. 2010 Apr 15;20(8):2474-7. doi: 10.1016/j.bmcl.2010.03.004. Epub 2010 Mar 10.

Authors

T K Sasikumar¹, Li Qiang, Duane A Burnett, William J Greenlee, Cheng Li, Mariagrazia Grilli, Rosalia Bertorelli, Gianluca Lozza, Angelo Reggiani

Affiliation

¹ Merck Research Laboratories, Kenilworth, NJ 07033, USA. [email protected]

PMID: 20346665
DOI: 10.1016/j.bmcl.2010.03.004

Abstract

A-ring modifications on the triazafluorenone core structure were investigated. Five membered heterocycles such as pyrazoles and isothiazoles are not tolerated. It has been found that the pyrimidine nucleus was very well tolerated on the left hand side. Amino pyrimidine compounds 24 and 27 showed acceptable PK profile with significant brain penetration. Compound 9 served as a versatile intermediate for a number of chemical transformations.

MeSH terms

Aza Compounds / chemistry*
Humans
Molecular Structure
Receptors, Metabotropic Glutamate / antagonists & inhibitors*

Substances

Aza Compounds
Receptors, Metabotropic Glutamate
metabotropic glutamate receptor type 1