- ATF6 MODULATORS AND USES THEREOF
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Compounds (I) as modulators of Activating Transcription Factor 6 (ATF6) are provided. The compounds may find use as therapeutic agents for the treatment of diseases or disorders mediated by ATF6 and may find particular use in the treatment of viral infections, neurodegenerative diseases, vascular diseases, or cancer.
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Paragraph 172
(2021/04/17)
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- Design, synthesis and structure-activity relationship study of aminopyridine derivatives as novel inhibitors of Janus kinase 2
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Janus Kinase 2 (JAK2) is a kind of intracellular non-receptor protein tyrosine kinase and has been certified as an important target for the treatment of myeloproliferative neoplasms and rheumatoid arthritis. However, the low selectivity and potential safety issues restrict the clinical applications of JAK2 inhibitors. Here we found that crizotinib showed good inhibitory activity against JAK2 by enzymatic assays (IC50 = 27 nM). Then we carried out structure-based drug design and synthesized a series of compounds with an aminopyridine scaffold. Finally, compound 12k and 12l were identified as the promising inhibitors of JAK2, which exhibited high inhibitory activity (IC50 = 6 nM and 3 nM, respectively) and selectivity for JAK2 over JAK1 and JAK3, and showed potent antiproliferative activities toward HEL human erythroleukemia cells. Moreover, 12k suppressed symptoms of the collagen-induced arthritis (CIA) model in rats.
- Wang, Wanqi,Diao, Yanyan,Li, Wenjie,Luo, Yating,Yang, Tingyuan,Zhao, Yuyu,Qi, TianTian,Xu, Fangling,Ma, Xiangyu,Ge, Huan,Liang, Yingfan,Zhao, Zhenjiang,Liang, Xin,Wang, Rui,Zhu, Lili,Li, Honglin,Xu, Yufang
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supporting information
p. 1507 - 1513
(2019/04/17)
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- Versatile Catalytic Hydrogenation Using A Simple Tin(IV) Lewis Acid
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Despite the rapid development of frustrated Lewis pair (FLP) chemistry over the last ten years, its application in catalytic hydrogenations remains dependent on a narrow family of structurally similar early main-group Lewis acids (LAs), inevitably placing limitations on reactivity, sensitivity and substrate scope. Herein we describe the FLP-mediated H2activation and catalytic hydrogenation activity of the alternative LA iPr3SnOTf, which acts as a surrogate for the trialkylstannylium ion iPr3Sn+, and is rapidly and easily prepared from simple, inexpensive starting materials. This highly thermally robust LA is found to be competent in the hydrogenation of a number of different unsaturated functional groups (which is unique to date for main-group FLP LAs not based on boron), and also displays a remarkable tolerance to moisture.
- Scott, Daniel J.,Phillips, Nicholas A.,Sapsford, Joshua S.,Deacy, Arron C.,Fuchter, Matthew J.,Ashley, Andrew E.
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supporting information
p. 14738 - 14742
(2016/11/23)
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- PRODUCTION METHOD OF OPTICALLY ACTIVE SECONDARY ALCOHOL
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PROBLEM TO BE SOLVED: To provide a chemical catalytic method allowing efficient production of a corresponding optically active secondary alcohol from an aromatic ketone having a substituent at each of two β-positions in an aromatic ring to the carbonyl site, so that both enantiomers can be separately made. SOLUTION: A production method of optically active secondary alcohol is characterized by reacting a ketone compound such as acetophenone derivatives with hydrogen in the presence of a ruthenium complex catalyst having an optically active diphosphine ligand. COPYRIGHT: (C)2015,JPO&INPIT
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Paragraph 0132; 0152; 0153
(2016/11/14)
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- Friedel-crafts reaction of benzyl fluorides: Selective activation of C-f bonds as enabled by hydrogen bonding
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A Friedel-Crafts benzylation of arenes with benzyl fluorides has been developed. The reaction produces 1,1-diaryl alkanes in good yield under mild conditions without the need for a transition metal or a strong Lewis acid. A mechanism involving activation of the C-F bond through hydrogen bonding is proposed. This mode of activation enables the selective reaction of benzylic C-F bonds in the presence of other benzylic leaving groups.
- Champagne, Pier Alexandre,Benhassine, Yasmine,Desroches, Justine,Paquin, Jean-Franois
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supporting information
p. 13835 - 13839
(2015/02/05)
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- Novel 6-aminofuro[3,2-c]pyridines as potent, orally efficacious inhibitors of cMET and RON kinases
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A series of novel 6-aminofuro[3,2-c]pyridines as kinase inhibitors is described, most notably, OSI-296 (6). We discuss our exploration of structure-activity relationships and optimization leading to OSI-296 and disclose its pharmacological activity against cMET and RON in cellular assays. OSI-296 is a potent and selective inhibitor of cMET and RON kinases that shows in vivo efficacy in tumor xenografts models upon oral dosing and is well tolerated.
- Steinig, Arno G.,Li, An-Hu,Wang, Jing,Chen, Xin,Dong, Hanqing,Ferraro, Caterina,Jin, Meizhong,Kadalbajoo, Mridula,Kleinberg, Andrew,Stolz, Kathryn M.,Tavares-Greco, Paula A.,Wang, Ti,Albertella, Mark R.,Peng, Yue,Crew, Linda,Kahler, Jennifer,Kan, Julie,Schulz, Ryan,Cooke, Andy,Bittner, Mark,Turton, Roy W.,Franklin, Maryland,Gokhale, Prafulla,Landfair, Darla,Mantis, Christine,Workman, Jen,Wild, Robert,Pachter, Jonathan,Epstein, David,Mulvihill, Mark J.
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p. 4381 - 4387
(2013/07/26)
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- Relationship between the structure and enantioselectivity in the asymmetric reduction of 2′,6′-disubstituted acetophenones with DIP-Chloride. An ab initio study
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Using computational and chemical studies, a relationship between the % ee achieved and the dihedral angles between the plane of the aromatic ring and the plane containing the carbonyl group has been established for asymmetric reductions with B-chlorodiisopinocampheylborane.
- Ramachandran, P. Veeraraghavan,Gong, Baoqing,Brown, Herbert C.,Francisco, Joseph S.
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p. 2603 - 2605
(2007/10/03)
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- Acceleration effects of phosphine ligands in the nickel catalyzed methylation of aldehydes using trimethylaluminum
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A nickel catalyzed methylation of aldehydes was conducted successfully using trimethylaluminum as an alkylation reagent. In the presence of a phosphine or phosphite ligand, the reaction was considerably accelerated to give the methylation product in good yields.
- Ichiyanagi, Tsuyoshi,Kuniyama, Satoru,Shimizu, Makoto,Fujisawa, Tamotsu
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p. 1033 - 1034
(2007/10/03)
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- 1-(2,6-Dichlorophenyl)ethylamine: A new and efficient chiral auxiliary for the Staudinger β-lactam synthesis
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The diastereoselective synthesis of β-lactams by the Staudinger reaction was examined using chiral imines, derived from substituted 1-phenylethylamines. Among them, 1-(2,6-dichlorophenyl)ethylamine was found to be a new and efficient chiral auxiliary, and the corresponding cis-β-lactams were obtained in good to excellent yields with high diastereoselectivity.
- Hashimoto, Yukihiko,Kai, Akiyoshi,Saigo, Kazuhiko
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p. 8821 - 8824
(2007/10/02)
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- REACTIONS OF 2,4- AND 2,6-DICHLOROPHENACYLIDENE HALIDES WITH TRIALKYLPHOSPHITES IN PROTIC SOLVENTS. DIRECT EVIDENCE FOR THE "ENOLATE ANION" PATHWAY
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The reactions of 2,6-dichlorophenacyl and 2,6-dichlorophenacylidene chlorides and bromides with trimethyl and triethyl phosphites have been investigated.The reactivity of 2,6-dichlorophenacylidene chloride and bromide towards trialkyl phosphites was compared with that of 2,4-dichlorophenacylidene chloride and bromide.The influence of methanol, acting as a model protic solvent, on the above mentioned processes has also benn investigated.The mechanism of Perkow reaction of sterically hindered α-haloketones with bulky substituents around the carbonyl center is discussed.
- Mlotkowska, Barbara,Majewski, Piotr,Koziara, Anna,Zwierzak, Andrzej,Sledzinski, Bohdan
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p. 631 - 642
(2007/10/02)
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