Parallel Optimization of Potency and Pharmacokinetics Leading to the Discovery of a Pyrrole Carboxamide ERK5 Kinase Domain Inhibitor was written by Miller, Duncan C.;Reuillon, Tristan;Molyneux, Lauren;Blackburn, Timothy;Cook, Simon J.;Edwards, Noel;Endicott, Jane A.;Golding, Bernard T.;Griffin, Roger J.;Hardcastle, Ian;Harnor, Suzannah J.;Heptinstall, Amy;Lochhead, Pamela;Martin, Mathew P.;Martin, Nick C.;Myers, Stephanie;Newell, David R.;Noble, Richard A.;Phillips, Nicole;Rigoreau, Laurent;Thomas, Huw;Tucker, Julie A.;Wang, Lan-Zhen;Waring, Michael J.;Wong, Ai-Ching;Wedge, Stephen R.;Noble, Martin E. M.;Cano, Celine. And the article was included in Journal of Medicinal Chemistry in 2022.Name: tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate This article mentions the following:
The nonclassical extracellular signal-related kinase 5 (ERK5) mitogen-activated protein kinase pathway has been implicated in increased cellular proliferation, migration, survival, and angiogenesis; hence, ERK5 inhibition may be an attractive approach for cancer treatment. However, the development of selective ERK5 inhibitors has been challenging. Previously, we described the development of a pyrrole carboxamide high-throughput screening hit into a selective, submicromolar inhibitor of ERK5 kinase activity. Improvement in the ERK5 potency was necessary for the identification of a tool ERK5 inhibitor for target validation studies. Herein, we describe the optimization of this series to identify nanomolar pyrrole carboxamide inhibitors of ERK5 incorporating a basic center, which suffered from poor oral bioavailability. Parallel optimization of potency and in vitro pharmacokinetic parameters led to the identification of a nonbasic pyrazole analog with an optimal balance of ERK5 inhibition and oral exposure. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (cas: 119285-07-3Name: tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate).
tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (cas: 119285-07-3) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Name: tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics