73278-90-7Relevant academic research and scientific papers
Discovery and Structural Optimization of 4-(Aminomethyl)benzamides as Potent Entry Inhibitors of Ebola and Marburg Virus Infections
Gaisina, Irina N.,Peet, Norton P.,Wong, Letitia,Schafer, Adam M.,Cheng, Han,Anantpadma, Manu,Davey, Robert A.,Thatcher, Gregory R. J.,Rong, Lijun
, p. 7211 - 7225 (2020/09/11)
The recent Ebola epidemics in West Africa underscore the great need for effective and practical therapies for future Ebola virus outbreaks. We have discovered a new series of remarkably potent small molecule inhibitors of Ebola virus entry. These 4-(aminomethyl)benzamide-based inhibitors are also effective against Marburg virus. Synthetic routes to these compounds allowed for the preparation of a wide variety of structures, including a conformationally restrained subset of indolines (compounds 41-50). Compounds 20, 23, 32, 33, and 35 are superior inhibitors of Ebola (Mayinga) and Marburg (Angola) infectious viruses. Representative compounds (20, 32, and 35) have shown good metabolic stability in plasma and liver microsomes (rat and human), and 32 did not inhibit CYP3A4 nor CYP2C9. These 4-(aminomethyl)benzamides are suitable for further optimization as inhibitors of filovirus entry, with the potential to be developed as therapeutic agents for the treatment and control of Ebola virus infections.
Discovery of a Benzamide Derivative That Protects Pancreatic β-Cells against Endoplasmic Reticulum Stress
Duan, Hongliang,Li, Yu,Arora, Daleep,Xu, Depeng,Lim, Hui-Ying,Wang, Weidong
, p. 6191 - 6204 (2017/08/02)
Endoplasmic reticulum (ER) stress-mediated pancreatic insulin-producing β-cell dysfunction and death are critical elements in the onset and progression of both type 1 and type 2 diabetes. Here, through cell-based high throughput screening we identified be
Synthesis and in Vitro Anticancer Activity of the First Class of Dual Inhibitors of REV-ERBβ and Autophagy
Torrente, Esther,Parodi, Chiara,Ercolani, Luisa,De Mei, Claudia,Ferrari, Alessio,Scarpelli, Rita,Grimaldi, Benedetto
supporting information, p. 5900 - 5915 (2015/08/24)
Autophagy inhibition is emerging as a promising anticancer strategy. We recently reported that the circadian nuclear receptor REV-ERBβ plays an unexpected role in sustaining cancer cell survival when the autophagy flux is compromised. We also identified 4-[[[1-(2-fluorophenyl)cyclopentyl]amino]methyl]-2-[(4-methylpiperazin-1-yl)methyl]phenol, 1 (ARN5187), as a novel dual inhibitor of REV-ERBβ and autophagy. 1 had improved cytotoxicity against BT-474 breast cancer cells compared to chloroquine, a clinically relevant autophagy inhibitor. Here, we present the results of structure-activity studies, based around 1, that disclose the first class of dual inhibitors of REV-ERBβ and autophagy. This study led to identification of 18 and 28, which were more effective REV-ERBβ antagonists than 1 and were more cytotoxic to BT-474. The combination of optimal chemical and structural moieties of these analogs generated 30, which elicited 15-fold greater REV-ERBβ inhibitory and cytotoxic activities compared to 1. Furthermore, 30 induced death in a panel of tumor cell lines at doses 5-50 times lower than an equitoxic amount of chloroquine but did not affect the viability of normal mammary epithelial cells.
DIARYLALKYLAMINE REV-ERB ANTAGONISTS AND THEIR USE AS MEDICAMENTS
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Page/Page column 44; 45; 66; 67; 79, (2015/04/28)
The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof : It further discloses a pharmaceutical composition comprising the compounds of Formula (I) and their uses as anti-proliferative and pro-apoptotic agents for cancer therapy.
Design, synthesis and AChE inhibitory activity of indanone and aurone derivatives
Sheng, Rong,Xu, Yu,Hu, Chunqi,Zhang, Jing,Lin, Xiao,Li, Jingya,Yang, Bo,He, Qiaojun,Hu, Yongzhou
experimental part, p. 7 - 17 (2009/04/06)
A new series of indanone and aurone derivatives have been synthesized and tested for in vitro AChE inhibitory activity by modified Ellman method. Most of them exhibit AChE inhibitory activities superior to rivastigmine. Further, the most potent compound 1g was selected to evaluate the effect on the acquisition and memory impairment by mice step-down passive avoidance test.
Scope of aminomethylations via Suzuki-Miyaura cross-coupling of orsanotrifluoroborates
Molander, Gary A.,Gormisky, Paul E.,Sandrock, Deidre L.
, p. 2052 - 2057 (2008/09/19)
(Chemical Equation Presented) We previously reported the Suzuki-Miyaura reaction of N,N-dialkylaminomethyltrifluoroborates with aryl bromides. Herein, we report a further investigation of the scope and limitations of this palladium-catalyzed aminomethylation reaction. Aryl chlorides, iodides, and triflates coupled in good to excellent yields to give N,N-dialkylbenzylic amines. The aminomethylation of alkenyl bromides was also examined.
1,2,4-TRIAZOLE-3,5-DIAMINE DERIVATIVES
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, (2008/06/13)
The invention relates to compounds of the formula (I) STR1 and physiologically acceptable salts, hydrates and bioprecursors thereof, in whichR 1 and R 2 represent hydrogen, an aliphatic or cycloaliphatic group, or R 1 and R 2 together with the nitrogen atom form a 5 to 10 membered heterocyclic ring:Alk represents a straight or branched alkylene chain;Q represents furan, thiophen or benzene ring which is incorporated into the rest of the molecule; X represents--CH 2--, STR2--O--or--S--where R 6 represents hydrogen or methyl;n represents zero, 1 or 2; m represents 2, 3 or 4;R 3 represents hydrogen, a substituted or unsubstituted aliphatic or aryl group and;R 4 and R 5, which may be the same or different, each represent hydrogen, a substituted or unsubstituted aliphatic, aryl, or together with the nitrogen atom form a heterocyclic group.
