Hinge Binder Scaffold Hopping Identifies Potent Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2) Inhibitor Chemotypes was written by Eduful, Benjamin J.;O’Byrne, Sean N.;Temme, Louisa;Asquith, Christopher R. M.;Liang, Yi;Picado, Alfredo;Pilotte, Joseph R.;Hossain, Mohammad Anwar;Wells, Carrow I.;Zuercher, William J.;Catta-Preta, Carolina M. C.;Zonzini Ramos, Priscila;Santiago, Andre de S.;Counago, Rafael M.;Langendorf, Christopher G.;Nay, Kevin;Oakhill, Jonathan S.;Pulliam, Thomas L.;Lin, Chenchu;Awad, Dominik;Willson, Timothy M.;Frigo, Daniel E.;Scott, John W.;Drewry, David H.. And the article was included in Journal of Medicinal Chemistry in 2021.Safety of 5-Chloro-3-iodopyrazolo[1,5-a]pyrimidine This article mentions the following:
CAMKK2 is a serine/threonine kinase and an activator of AMPK whose dysregulation is linked with multiple diseases. Unfortunately, STO-609, the tool inhibitor commonly used to probe CAMKK2 signaling, has limitations. To identify promising scaffolds as starting points for the development of high-quality CAMKK2 chem. probes, we utilized a hinge-binding scaffold hopping strategy to design new CAMKK2 inhibitors. Starting from the potent but promiscuous disubstituted 7-azaindole GSK650934, a total of 32 compounds, composed of single-ring, 5,6-, and 6,6-fused heteroaromatic cores, were synthesized. The compound set was specifically designed to probe interactions with the kinase hinge-binding residues. Compared to GSK650394 and STO-609, 13 compounds displayed similar or better CAMKK2 inhibitory potency in vitro, while compounds 13g and 45 had improved selectivity for CAMKK2 across the kinome. Our systematic survey of hinge-binding chemotypes identified several potent and selective inhibitors of CAMKK2 to serve as starting points for medicinal chem. programs. In the experiment, the researchers used many compounds, for example, 5-Chloro-3-iodopyrazolo[1,5-a]pyrimidine (cas: 923595-58-8Safety of 5-Chloro-3-iodopyrazolo[1,5-a]pyrimidine).
5-Chloro-3-iodopyrazolo[1,5-a]pyrimidine (cas: 923595-58-8) belongs to iodide derivatives. Organic iodides are widely used in organic synthesis. Halogenation of aromatic hydrocarbons is a very important reaction via an electrophilic aromatic substitution. Alkyl iodides react at a faster rate than alkyl fluorides due to the weak C-I bond.Safety of 5-Chloro-3-iodopyrazolo[1,5-a]pyrimidine
Referemce:
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com