- PRMT5 INHIBITORS
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The present invention provides a compound of Formula (I) and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are PRMT5 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat cancer, sickle cell, and hereditary persistence of foetal hemoglobin (HPFH) mutations.
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- Design and synthesis of novel androgen receptor antagonists via molecular modeling
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Several androgen receptor (AR) antagonists are clinically prescribed to treat prostate cancer. Unfortunately, many patients become resistant to the existing AR antagonists. To overcome this, a novel AR antagonist candidate called DIMN was discovered by our research group in 2013. In order to develop compounds with improved potency, we designed novel DIMN derivatives based on a docking study and substituted carbons with heteroatom moieties. Encouraging in vitro results for compounds 1b, 1c, 1e, 3c, and 4c proved that the new design was successful. Among the newly synthesized compounds, 1e exhibited the strongest inhibitory effect on LNCaP cell growth (IC50= 0.35 μM) and also acted as a competitive AR antagonist with selectivity over the estrogen receptor (ER) and the glucocorticoid receptor (GR). A docking study of compound 1e fully supported these biological results. Compound 1e is considered to be a novel, potent and AR-specific antagonist for treating prostate cancer. Thus, our study successfully applied molecular modeling and bioisosteric replacement for hit optimization. The methods here provide a guide for future development of drug candidates through structure-based drug discovery and chemical modifications.
- Zhao, Chao,Choi, You Hee,Khadka, Daulat Bikram,Jin, Yifeng,Lee, Kwang-Youl,Cho, Won-Jea
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p. 789 - 801
(2016/05/24)
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- SUBSTITUTED TETRAHYDROISOQUINOLINE COMPOUNDS AS FACTOR XIA INHIBITORS
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The present invention provides compounds of Formula (I): or stereoisomers, pharmaceutically acceptable salts thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of factor XIa and/or plasma kallikrein which may be used as medicaments.
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Paragraph 00298
(2013/04/25)
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- The remarkable effect of a simple ion: Iodide-promoted transfer hydrogenation of heteroaromatics
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I can do it! Accelerated by simple iodide ions, rhodium-catalysed transfer hydrogenation can be readily performed on quinolines, isoquinolines and quinoxalines, affording the tetrahydro products in high yields with low catalyst loading (see scheme). Copyright
- Wu, Jianjun,Wang, Chao,Tang, Weijun,Pettman, Alan,Xiao, Jianliang
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supporting information; experimental part
p. 9525 - 9529
(2012/08/28)
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- SUBSTITUTED PROPIOLIC ACID AMIDES AND THEIR USE FOR PRODUCING DRUGS
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The present invention relates to substituted propiolic acid amides, to methods for the production thereof, to medicaments containing these compounds and to the use thereof for producing medicaments.
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Page/Page column 35
(2009/04/24)
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- Friedel-crafts cyclization of N,N-dibenzylethylenediamines
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An efficient synthesis of substituted 1,2,3,4-tetrahydroisoquinolines is described. N,N-dibenzylethylenediamines smoothly under go Friedel-Crafts cyclization in the presence of anhydrous aluminum chloride in decalin to give 1,2,3,4-tetrahydroisoquinolines.
- Peerzada
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p. 2533 - 2538
(2007/10/03)
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