Bagdanoff, Jeffrey, Jain, Rama, Han, Wooseok, Zhu, Shejin, Madera, Ann Marie, Lee, Patrick and Poon, Daniel (2015) Tetrahydropyrrolo-diazepenones as inhibitors of ERK2 kinase. Bioorganic and Medicinal Chemistry Letters, 25 (18). pp. 3788-3792. ISSN 14643405

Abstract

Abstract A series of structure based drug design hypotheses and focused screening efforts led to the identification of tetrahydropyrrolo-diazepenones with striking potency against ERK2 kinase. The role of fluorination in mitigating microsomal clearance was systematically explored. Ultimately, it was found that fluorination of a cyclopentanol substructure provided significant improvement in both potency and human metabolic stability.

Item Type:	Article
Keywords:	ATP binding cleft ERK2 kinase Extraction ratio Lower-hinge lysine Structure based drug design
Date Deposited:	25 Nov 2017 00:45
Last Modified:	25 Jan 2019 00:45
URI:	https://oak.novartis.com/id/eprint/25620