Hansen, Bettina Borreschmidt; Jepsen, Tue Heesgaard; Larsen, Mogens; Sindet, Rikke; Vifian, Thomas; Burhardt, Mia Noerreskov; Larsen, Jens; Seitzberg, Jimmi Gerner; Carnerup, Martin A.; Jerre, Anders; Moelck, Christina; Lovato, Paola; Rai, Sanjay; Nasipireddy, Venkatarathnam Reddy; Ritzen, Andreas published an article in Journal of Medicinal Chemistry. The title of the article was 《Fragment-Based Discovery of Pyrazolopyridones as JAK1 Inhibitors with Excellent Subtype Selectivity》.SDS of cas: 1220695-06-6 The author mentioned the following in the article:
Herein, we report the discovery of a series of JAK1-selective kinase inhibitors with high potency and excellent JAK family subtype selectivity. A fragment screening hit 1 with a pyrazolopyridone core and a JAK1 bias was selected as the starting point for our fragment-based lead generation efforts. A two-stage strategy was chosen with the dual aims of improving potency and JAK1 selectivity: Optimization of the lipophilic ribose pocket-targeting substituent was followed by the introduction of a variety of P-loop-targeting functional groups. Combining the best moieties from both stages of the optimization afforded compound 40(I), which showed excellent potency and selectivity. Metabolism studies in vitro and in vivo together with an in vitro safety evaluation suggest that 40 may be a viable lead compound for the development of highly subtype-selective JAK1 inhibitors. In addition to this study using Cyclobutylmethanesulfonyl chloride, there are many other studies that have used Cyclobutylmethanesulfonyl chloride(cas: 1220695-06-6SDS of cas: 1220695-06-6) was used in this study.
Cyclobutylmethanesulfonyl chloride(cas: 1220695-06-6) is a mumber of cyclobutanes. In contrast to cyclopropane, cyclobutane is not planar but “puckered”. Puckering, which occurs when hydrogen atoms are twisted away from each other, reduces hydrogen–hydrogen eclipsing interactions. This twisting does not produce a fully staggered arrangement of hydrogen atoms because the decrease in torsional strain energy is balanced by some increase in the bond angle strain.SDS of cas: 1220695-06-6
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics