881401-96-3Relevant academic research and scientific papers
Base-Free Pd-Catalyzed C?Cl Borylation of Fluorinated Aryl Chlorides
Budiman, Yudha P.,Lorenzen, Sabine,Liu, Zhiqiang,Radius, Udo,Marder, Todd B.
supporting information, p. 3869 - 3874 (2021/02/03)
Catalytic C?X borylation of aryl halides containing two ortho-fluorines has been found to be challenging, as most previous methods require stoichiometric amounts of base and the polyfluorinated aryl boronates suffer from protodeboronation, which is accele
Copper-Catalyzed Oxidative Cross-Coupling of Electron-Deficient Polyfluorophenylboronate Esters with Terminal Alkynes
Liu, Zhiqiang,Budiman, Yudha P.,Tian, Ya-Ming,Friedrich, Alexandra,Huang, Mingming,Westcott, Stephen A.,Radius, Udo,Marder, Todd B.
supporting information, p. 17267 - 17274 (2020/12/01)
We report herein a mild procedure for the copper-catalyzed oxidative cross-coupling of electron-deficient polyfluorophenylboronate esters with terminal alkynes. This method displays good functional group tolerance and broad substrate scope, generating cro
Discovery of S64315, a Potent and Selective Mcl-1 Inhibitor
Szlavik, Zoltan,Csekei, Marton,Paczal, Attila,Szabo, Zoltan B.,Sipos, Szabolcs,Radics, Gabor,Proszenyak, Agnes,Balint, Balazs,Murray, James,Davidson, James,Chen, Ijen,Dokurno, Pawel,Surgenor, Allan E,Daniels, Zoe Marie,Hubbard, Roderick E.,Le Toumelin-Braizat, Ga?tane,Claperon, Audrey,Lysiak-Auvity, Ga?lle,Girard, Anne-Marie,Bruno, Alain,Chanrion, Maia,Colland, Frédéric,Maragno, Ana-Leticia,Demarles, Didier,Geneste, Olivier,Kotschy, Andras
, p. 13762 - 13795 (2020/12/02)
Myeloid cell leukemia 1 (Mcl-1) has emerged as an attractive target for cancer therapy. It is an antiapoptotic member of the Bcl-2 family of proteins, whose upregulation in human cancers is associated with high tumor grade, poor survival, and resistance to chemotherapy. Here we report the discovery of our clinical candidate S64315, a selective small molecule inhibitor of Mcl-1. Starting from a fragment derived lead compound, we have conducted structure guided optimization that has led to a significant (3 log) improvement of target affinity as well as cellular potency. The presence of hindered rotation along a biaryl axis has conferred high selectivity to the compounds against other members of the Bcl-2 family. During optimization, we have also established predictive PD markers of Mcl-1 inhibition and achieved both efficient in vitro cell killing and tumor regression in Mcl-1 dependent cancer models. The preclinical candidate has drug-like properties that have enabled its development and entry into clinical trials.
Cobalt-Catalyzed Regioselective Borylation of Arenes: N-Heterocyclic Silylene as an Electron Donor in the Metal-Mediated Activation of C?H Bonds
Ren, Hailong,Zhou, Yu-Peng,Bai, Yunping,Cui, Chunming,Driess, Matthias
supporting information, p. 5663 - 5667 (2017/04/28)
C?H Borylation of arenes has been a subject of great interest recently because of its atom-economy and the wide applicability of borylated products in value-added synthesis. A new bis(silylene)cobalt(II) complex bearing a bis(N-heterocyclic silylene)-pyridine pincer ligand (SiNSi) has been synthesized and structurally characterized. It enabled the regioselective catalytic C?H borylation of pyridines, furans, and fluorinated arenes. Notably, it exhibited complementary regioselectivity for the borylation of fluorinated arenes compared to previously known catalytic systems, demonstrating that N-heterocyclic silylene donors have enormous potential in metal-catalyzed catalytic applications.
