- Structure-Based Design of Tetrahydroisoquinoline-7-carboxamides as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors
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The structure-based design of 1, 2, 3, 4-tetrahydroisoquinoline derivatives as selective DDR1 inhibitors is reported. One of the representative compounds, 6j, binds to DDR1 with a Kd value of 4.7 nM and suppresses its kinase activity with an IC50 value of 9.4 nM, but it is significantly less potent for a panel of 400 nonmutated kinases. 6j also demonstrated reasonable pharmacokinetic properties and a promising oral therapeutic effect in a bleomycin-induced mouse pulmonary fibrosis model.
- Wang, Zhen,Bian, Huan,Bartual, Sergio G.,Du, Wenting,Luo, Jinfeng,Zhao, Hu,Zhang, Shasha,Mo, Cheng,Zhou, Yang,Xu, Yong,Tu, Zhengchao,Ren, Xiaomei,Lu, Xiaoyun,Brekken, Rolf A.,Yao, Libo,Bullock, Alex N.,Su, Jin,Ding, Ke
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- HISTONE DEACETYLASE INHIBITORS
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Provided herein are isoform selective histone deacetylase inhibitors of the formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, metabolites, prodrugs, solvates, pharmaceutically acceptable salts and compositions thereof. These compounds are isoform selective inhibitors of HDACs and are useful as a therapeutic or ameliorating agent for diseases that are involved in cellular growth such as cancer, malignant tumors, autoimmune diseases, skin diseases, fungal infections, protozoal infections, HIV, inflammation and CNS disorders.
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Page/Page column 38
(2012/09/21)
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- SHORT ACTING PHENYLALKYLAMINE CALCIUM CHANNEL BLOCKERS AND USES THEREOF
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The present invention relates to the use of a pharmaceutically effective amount of an short-acting calcium channel blocking compound to treat ischemic heart conditions, cardiac arrhythmias, hypertensive crisis in an emergency room setting, hypertension before, during, or after surgery, no- reflow phenomenon following reperfusion, and diseases associated with decreased skeletal muscle blood flow. The invention also relates to pharmaceutical compositions formulated for use in such methods and to kits for such methods.
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- Preparation of 1,2,3,4-tetrahydroisoquinolines lacking electron donating groups - An intramolecular cyclization complementary to the Pictet-Spengler reaction
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The synthesis of 1,2,3,4-tetrahydroisoquinolines via an intramolecular cyclization of N-trifluoroacylated phenethylamines devoid of electron donating groups, with paraformaldehyde mediated by acetic/sulfuric acid milieu is described.
- Stokker
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p. 5453 - 5456
(2007/10/03)
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