Browse views: by Year, by Function, by GLF, by Subfunction, by Conference, by Journal

Highly ligand efficient tetrahydro-pyrazolopyridines as inhibitors of ERK2 kinase

Bagdanoff, Jeffrey and Jain, Rama and Han, Wooseok and Ding, Yu and Poon, Daniel and 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

Search

Email Alerts

Register with OAK to receive email alerts for saved searches.