Benzyl prolinate derivatives as novel selective KCC2 blockers

Cécile Pégurier; Nathalie Bosman; Philippe Collart; Marie-Laure Delporte; Karine Leclercq; Sébastien Lengelé; Ananda Kumar Kanduluru; Stéphane Meunier; Nathalie Pacico; Lakshmana Rao Vadali; Alain Wagner; Christian Wolff; Laurent Provins

doi:10.1016/j.bmcl.2010.02.092

Benzyl prolinate derivatives as novel selective KCC2 blockers

Bioorg Med Chem Lett. 2010 Apr 15;20(8):2542-5. doi: 10.1016/j.bmcl.2010.02.092. Epub 2010 Mar 1.

Authors

Cécile Pégurier¹, Nathalie Bosman, Philippe Collart, Marie-Laure Delporte, Karine Leclercq, Sébastien Lengelé, Ananda Kumar Kanduluru, Stéphane Meunier, Nathalie Pacico, Lakshmana Rao Vadali, Alain Wagner, Christian Wolff, Laurent Provins

Affiliation

¹ UCB Pharma SA, UCB NewMedicines, Chemin du Foriest, B-1420 Braine-L'Alleud, Belgium.

PMID: 20299216
DOI: 10.1016/j.bmcl.2010.02.092

Abstract

The discovery and optimization of a novel class of selective submicromolar KCC2 blockers is described. Details of synthesis and SAR are given together with ADME properties of selected compounds. A methylsulfone residue on the R(1) phenyl group improved the overall general profile of these prolinate derivatives.

Publication types

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

MeSH terms

Animals
K Cl- Cotransporters
Proline / analogs & derivatives*
Proline / chemistry
Proline / pharmacology
Rats
Stereoisomerism
Structure-Activity Relationship
Symporters / antagonists & inhibitors*

Substances

Symporters
Proline