Majumdar, Dyuti, Chin, Donovan, Fortin, Pascal, Feng, Yun, Gould, Ty, Kirby, Christina, Shao, Wenlin, Stams, Travis, Waters, Nigel and Shultz, Michael (2013) Structure-efficiency relationship of [1,2,4]triazol-3-ylamines as novel nicotinamide isosteres that inhibit tankyrases. Journal of Medicinal Chemistry, 56 (17). pp. 7049-7059. ISSN 0022-2623

Abstract

Tankyrases 1 and 2 are members of the poly(ADP-ribose) polymerase (PARP) family of enzymes that modulate Wnt pathway signaling. While amide- and lactam-based nicotinamide mimetics that inhibit tankyrase activity, such as XAV939, are well-known, herein we report the discovery and evaluation of a novel nicotinamide isostere that demonstrates selectivity over other PARP family members. We demonstrate the utilization of lipophilic efficiency-based structure-efficiency relationships (SER) to rapidly drive the evaluation of this series. These efforts led to a series of selective, cell-active compounds with solubility, physicochemical, and in vitro properties suitable for further optimization. © 2013 American Chemical Society.

Item Type:	Article
Date Deposited:	25 Nov 2017 00:45
Last Modified:	25 Jan 2019 00:46
URI:	https://oak.novartis.com/id/eprint/9678