21120-74-1Relevant articles and documents
Beyond Basicity: Discovery of Nonbasic DENV-2 Protease Inhibitors with Potent Activity in Cell Culture
Kühl, Nikos,Leuthold, Mila M.,Behnam, Mira A. M.,Klein, Christian D.
, p. 4567 - 4587 (2021/05/06)
The viral serine protease NS2B-NS3 is one of the promising targets for drug discovery against dengue virus and other flaviviruses. The molecular recognition preferences of the protease favor basic, positively charged moieties as substrates and inhibitors, which leads to pharmacokinetic liabilities and off-target interactions with host proteases such as thrombin. We here present the results of efforts that were aimed specifically at the discovery and development of noncharged, small-molecular inhibitors of the flaviviral proteases. A key factor in the discovery of these compounds was a cellular reporter gene assay for the dengue protease, the DENV2proHeLa system. Extensive structure-activity relationship explorations resulted in novel benzamide derivatives with submicromolar activities in viral replication assays (EC50 0.24 μM), selectivity against off-target proteases, and negligible cytotoxicity. This structural class has increased drug-likeness compared to most of the previously published active-site-directed flaviviral protease inhibitors and includes promising candidates for further preclinical development.
Trimethoxyphenyl (TMP) as a Useful Auxiliary for in situ Formation and Reaction of Aryl(TMP)iodonium Salts: Synthesis of Diaryl Ethers
Gallagher, Rory T.,Basu, Souradeep,Stuart, David R.
, p. 320 - 325 (2019/12/11)
Herein, we describe a synthetic approach for arylation that exploits the in situ formation and reaction of an unsymmetrical diaryliodonium salt. In this way, aryl iodides are used as reagents in a metal-free reaction with phenols, and a trimethoxyphenyl (TMP) group is used as a “dummy” group to facilitate transfer of a wide range of aryl moieties. The scope of aryl electrophiles and phenol nucleophiles is broad (>30 examples) and the yields are high (52–95%, 80% avg.). One-pot coupling reactions avoid the synthesis of diaryliodonium salts and provide opportunities for sequential reactions and novel chemoselectivity. (Figure presented.).
INHIBITORS OF TRPC6
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Page/Page column 32; 48; 49, (2019/09/04)
The present invention relates to polycyclic compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1 to R4, R7 to R10, Y and A are as defined herein. The invention also relates to pharm
Synthesis and antiproliferative activity of novel 4-substituted-phenoxy-benzamide derivatives
Sun, Chi-Yu,Li, Yang-Sheng,Shi, Ai-Long,Li, Ya-Fei,Cao, Rui-Fang,Ding, Huai-Wei,Yin, Qing-Qing,Zhang, Li-Juan,Zheng, Hua-Chuan,Song, Hong-Rui
, p. 1307 - 1310 (2015/12/31)
A series of novel 4-substituted-phenoxy-benzamide derivatives bearing an aryl cycloaliphatic amine moiety were synthesized and evaluated for antiproliferative activity against SW620, HT29 and MGC803 cancer cell lines in vitro. The pharmacological data demonstrated that the majority of target compounds exhibited moderate efficacy in HT29 and MGC803 cell lines. Compound 10c showed promising inhibition of hedgehog (Hh) signaling pathway in an Hh-related assay. In addition, the superposition pattern of 10c showed a good fit for a pharmacophoric model generated by Hh inhibitors and provided a basis for further structural optimization.
BRUTON'S TYROSINE KINASE INHIBITORS
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Page/Page column 91; 161; 162, (2014/05/24)
Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions. (Formula I)
Ligand-free copper-catalyzed O-arylation of nitroarenes with phenols
Chen, Jiuxi,Wang, Xingyong,Zheng, Xingwang,Ding, Jinchang,Liu, Miaochang,Wu, Huayue
supporting information, p. 8905 - 8907 (2012/10/29)
The first example of ligand-free copper-catalyzed O-arylation of nitroarenes with phenols was developed, achieving unsymmetrical diaryl ethers in moderate to excellent yields. This arylation proceeded smoothly without promotion of the ligands, and displayed great functional group compatibility. Thus, the method represents a new, facile, and cost-effective approach to access unsymmetrical diaryl ethers.
Studies on Selective Nucleophilic Substitution Reactions of (+)PF6(-) Complexes: Applications to the Synthesis of Polymer Monomers
Pearson, Anthony J.,Gelormini, Ann M.
, p. 4561 - 4570 (2007/10/02)
Selective displacement of chloride from cyclopentadienyl(1,4-dichlorobenzene)iron(1+) by a series of aryl oxide and amine nucleophiles is described.The methodology, coupled with decomplexation of the product organometallics, allows access to a series of para-disubstituted benzene derivatives that are of potential value in the construction of unusual polymers.Four such compounds, derived from sequential addition of 4-hydroxybenzoic ester and hydroquinone or resorcinol monophenoxide to the 1,4- and 1,3-dichlorobenzene-FeCp complexes, were subjected to polyesterification reactions.Previously unreported isoregic poly(ether-esters) were prepared and characterized.
Analogues of clofibrate and clobuzarit containing fluorine in the side chains
Haydock,Mulholland,Telford,et al.
, p. 205 - 214 (2007/10/02)
A series of analogues of clofibrate and 2-[4-(4-chlorophenyl)phenylmethoxy]-2-methylpropionic acid (clobuzarit) has been prepared by replacing the methyl groups by trifluoromethyl groups and changing the aromatic moiety. The activity of these compounds has been assayed on the plasma levels of cholesterol, Total Esterified Fatty Acids (T.E.F.A.) and fibrinogen in rats. It appears that derivatives of the first series which contain only one trifluoromethyl group are hypocholesterolaemic and that many mono- of bis- trifluoromethyl derivatives of the second series lower the levels of both cholesterol and T.E.F.A. in contrast to clobuzarit.
