Bagdanoff, Jeffrey, Jain, Rama, Han, Wooseok, Ding, Yu, Poon, Daniel, Lee, Patrick and Lindvall, Mika (2015) Highly ligand efficient tetrahydro-pyrazolopyridines as inhibitors of ERK2 kinase. Bioorganic and Medicinal Chemistry Letters.

Abstract

A series of structure based drug design hypotheses and sequential screening efforts drove improvements in the potency and lipophilic efficiency of tetrahydro-pyrazolopyridine based ERK2 inhibitors. Fragment growing efforts of an early fragment lead established a new lipophilic Ph-Tyr interaction. Subsequent cleavage of a lipophilic moiety introduced a polar contact between a newly liberated N-H and a vicinal Asp, resulting in substantial improvements in the lipophilic efficiency and in vitro clearance.

Item Type:	Article
Date Deposited:	26 Apr 2016 23:45
Last Modified:	26 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/25644