1206248-85-2Relevant academic research and scientific papers
HETEROARYL AMIDES USEFUL AS KIF18A INHIBITORS
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Paragraph 0192-0194, (2020/07/14)
The present invention relates to chemical compounds having a general formula (I), as defined herein, and synthetic intermediates thereof, which are capable of modulating KIF18A protein thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of KIF18A.
Electrochemically Driven, Ni-Catalyzed Aryl Amination: Scope, Mechanism, and Applications
Kawamata, Yu,Vantourout, Julien C.,Hickey, David P.,Bai, Peng,Chen, Longrui,Hou, Qinglong,Qiao, Wenhua,Barman, Koushik,Edwards, Martin A.,Garrido-Castro, Alberto F.,Degruyter, Justine N.,Nakamura, Hugh,Knouse, Kyle,Qin, Chuanguang,Clay, Khalyd J.,Bao, Denghui,Li, Chao,Starr, Jeremy T.,Garcia-Irizarry, Carmen,Sach, Neal,White, Henry S.,Neurock, Matthew,Minteer, Shelley D.,Baran, Phil S.
supporting information, p. 6392 - 6402 (2019/04/17)
C-N cross-coupling is one of the most valuable and widespread transformations in organic synthesis. Largely dominated by Pd- and Cu-based catalytic systems, it has proven to be a staple transformation for those in both academia and industry. The current study presents the development and mechanistic understanding of an electrochemically driven, Ni-catalyzed method for achieving this reaction of high strategic importance. Through a series of electrochemical, computational, kinetic, and empirical experiments, the key mechanistic features of this reaction have been unraveled, leading to a second generation set of conditions that is applicable to a broad range of aryl halides and amine nucleophiles including complex examples on oligopeptides, medicinally relevant heterocycles, natural products, and sugars. Full disclosure of the current limitations and procedures for both batch and flow scale-ups (100 g) are also described.
Discovery of GDC-0853: A Potent, Selective, and Noncovalent Bruton's Tyrosine Kinase Inhibitor in Early Clinical Development
Crawford, James J.,Johnson, Adam R.,Misner, Dinah L.,Belmont, Lisa D.,Castanedo, Georgette,Choy, Regina,Coraggio, Melis,Dong, Liming,Eigenbrot, Charles,Erickson, Rebecca,Ghilardi, Nico,Hau, Jonathan,Katewa, Arna,Kohli, Pawan Bir,Lee, Wendy,Lubach, Joseph W.,McKenzie, Brent S.,Ortwine, Daniel F.,Schutt, Leah,Tay, Suzanne,Wei, Binqing,Reif, Karin,Liu, Lichuan,Wong, Harvey,Young, Wendy B.
supporting information, p. 2227 - 2245 (2018/03/26)
Bruton's tyrosine kinase (Btk) is a nonreceptor cytoplasmic tyrosine kinase involved in B-cell and myeloid cell activation, downstream of B-cell and Fcγ receptors, respectively. Preclinical studies have indicated that inhibition of Btk activity might offer a potential therapy in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Here we disclose the discovery and preclinical characterization of a potent, selective, and noncovalent Btk inhibitor currently in clinical development. GDC-0853 (29) suppresses B cell- and myeloid cell-mediated components of disease and demonstrates dose-dependent activity in an in vivo rat model of inflammatory arthritis. It demonstrates highly favorable safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles in preclinical and Phase 2 studies ongoing in patients with rheumatoid arthritis, lupus, and chronic spontaneous urticaria. On the basis of its potency, selectivity, long target residence time, and noncovalent mode of inhibition, 29 has the potential to be a best-in-class Btk inhibitor for a wide range of immunological indications.
NOVEL PIPERAZINE ANALOGS AS BROAD-SPECTRUM INFLUENZA ANTIVIRALS
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Page/Page column 55, (2012/03/27)
A compound of Formula (I) is set forth, including pharmaceutically acceptable salts thereof, wherein Het is a 5 or 6-membered heterocycle with -N, -O, or -S adjacent to the -Ar substituent or adjacent to the point of attachment for the -Ar substituent; Ar
