933218-96-3Relevant academic research and scientific papers
Structure-efficiency relationship of [1,2,4]triazol-3-ylamines as novel nicotinamide isosteres that inhibit tankyrases
Shultz, Michael D.,Majumdar, Dyuti,Chin, Donovan N.,Fortin, Pascal D.,Feng, Yun,Gould, Ty,Kirby, Christina A.,Stams, Travis,Waters, Nigel J.,Shao, Wenlin
, p. 7049 - 7059 (2013)
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.
