36096-74-9Relevant academic research and scientific papers
NITROGEN-CONTAINING HETEROCYCLIC COMPOUND AND COMPOSITION THEREOF, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
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Paragraph 0365-0366, (2021/10/07)
Disclosed by the present invention are a nitrogen-containing heterocyclic compound, and a composition thereof, a preparation method therefor and an application thereof. The structure of the nitrogen-containing heterocyclic compound according to the presen
Design and Discovery of N-(3-(2-(2-Hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methylphenyl)-2-(trifluoromethyl)isonicotinamide, a Selective, Efficacious, and Well-Tolerated RAF Inhibitor Targeting RAS Mutant Cancers: The Path to the Clinic
Ramurthy, Savithri,Taft, Benjamin R.,Aversa, Robert J.,Barsanti, Paul A.,Burger, Matthew T.,Lou, Yan,Nishiguchi, Gisele A.,Rico, Alice,Setti, Lina,Smith, Aaron,Subramanian, Sharadha,Tamez, Victoriano,Tanner, Huw,Wan, Lifeng,Hu, Cheng,Appleton, Brent A.,Mamo, Mulugeta,Tandeske, Laura,Tellew, John E.,Huang, Shenlin,Yue, Qin,Chaudhary, Apurva,Tian, Hung,Iyer, Raman,Hassan, A. Quamrul,Mathews Griner, Lesley A.,La Bonte, Laura R.,Cooke, Vesselina G.,Van Abbema, Anne,Merritt, Hanne,Gampa, Kalyani,Feng, Fei,Yuan, Jing,Mishina, Yuji,Wang, Yingyun,Haling, Jacob R.,Vaziri, Sepideh,Hekmat-Nejad, Mohammad,Polyakov, Valery,Zang, Richard,Sethuraman, Vijay,Amiri, Payman,Singh, Mallika,Sellers, William R.,Lees, Emma,Shao, Wenlin,Dillon, Michael P.,Stuart, Darrin D.
, p. 2013 - 2027 (2019/06/04)
Direct pharmacological inhibition of RAS has remained elusive, and efforts to target CRAF have been challenging due to the complex nature of RAF signaling, downstream of activated RAS, and the poor overall kinase selectivity of putative RAF inhibitors. Herein, we describe 15 (LXH254, Aversa, R.; et al. Int. Patent WO2014151616A1, 2014), a selective B/C RAF inhibitor, which was developed by focusing on drug-like properties and selectivity. Our previous tool compound, 3 (RAF709; Nishiguchi, G. A.; et al. J. Med. Chem. 2017, 60, 4969), was potent, selective, efficacious, and well tolerated in preclinical models, but the high human intrinsic clearance precluded further development and prompted further investigation of close analogues. A structure-based approach led to a pyridine series with an alcohol side chain that could interact with the DFG loop and significantly improved cell potency. Further mitigation of human intrinsic clearance and time-dependent inhibition led to the discovery of 15. Due to its excellent properties, it was progressed through toxicology studies and is being tested in phase 1 clinical trials.
Copper-catalyzed electrophilic amination of heteroarenes and arenes by C-H zincation
McDonald, Stacey L.,Hendrick, Charles E.,Wang, Qiu
supporting information, p. 4667 - 4670 (2014/05/20)
Direct amination of heteroarenes and arenes has been achieved in a one-pot C-H zincation/copper-catalyzed electrophilic amination procedure. This amination method provides an efficient and rapid approach to access a diverse range of heteroaromatic and aromatic amines including those previously inaccessible using C-H amination methods. The mild reaction conditions and good functional-group compatibility demonstrate its great potential for the synthesis of important and complex amines. Direct amination of heteroarenes and arenes has been achieved in a one-pot zincation/Cu(OAc)2-catalyzed amination sequence using O-acylhydroxylamines. The method provides a rapid and efficient approach to a range of aromatic and heteroaromatic amines, including those which were previously inaccessible by using C-H amination methods. tmp=2,2,6,6- tetramethylpiperidide.
Triazolo-pyridazine derivatives as ligands for GABA receptors
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, (2008/06/13)
1,2,4-triazolo[4,3-b]pyridazine derivatives, possessing an optionally substituted cycloalkyl, phenyl or heteroaryl substituent at the 3-position, a substituted alkoxy moiety at the 6-position, an optionally substituted N-linked nitrogen-containing aliphat
Substituted triazolo-pyridazine derivatives as ligands for GABA receptors
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, (2008/06/13)
Substituted triazolo-pyridazine derivative compounds represented by wherein the variables are disclosed herein are selective ligands for GABA-A receptors, particularly for the α2 and/or α3 subunits.
