677743-79-2Relevant academic research and scientific papers
Ruthenium Catalyzed Direct Asymmetric Reductive Amination of Simple Aliphatic Ketones Using Ammonium Iodide and Hydrogen
Ernst, Martin,Ghosh, Tamal,Hashmi, A. Stephen K.,Schaub, Thomas
supporting information, (2020/07/14)
The direct conversion of ketones into chiral primary amines is a key transformation in chemistry. Here, we present a ruthenium catalyzed asymmetric reductive amination (ARA) of purely aliphatic ketones with good yields and moderate enantioselectivity: up to 99 percent yield and 74 percent ee. The strategy involves [Ru(PPh3)3H(CO)Cl] in combination with the ligand (S,S)-f-binaphane as the catalyst, NH4I as the amine source and H2 as the reductant. This is a straightforward and user-friendly process to access industrially relevant chiral aliphatic primary amines. Although the enantioselectivity with this approach is only moderate, to the extent of our knowledge, the maximum ee of 74 percent achieved with this system is the highest reported till now apart from enzyme catalysis for the direct transformation of ketones into chiral aliphatic primary amines.
Discovery of Quinazolines That Activate SOS1-Mediated Nucleotide Exchange on RAS
Abbott, Jason R.,Patel, Pratiq A.,Howes, Jennifer E.,Akan, Denis T.,Kennedy, J. Phillip,Burns, Michael C.,Browning, Carrie F.,Sun, Qi,Rossanese, Olivia W.,Phan, Jason,Waterson, Alex G.,Fesik, Stephen W.
supporting information, p. 941 - 946 (2018/09/06)
Proteins in the RAS family are important regulators of cellular signaling and, when mutated, can drive cancer pathogenesis. Despite considerable effort over the last 30 years, RAS proteins have proven to be recalcitrant therapeutic targets. One approach for modulating RAS signaling is to target proteins that interact with RAS, such as the guanine nucleotide exchange factor (GEF) son of sevenless homologue 1 (SOS1). Here, we report hit-to-lead studies on quinazoline-containing compounds that bind to SOS1 and activate nucleotide exchange on RAS. Using structure-based design, we refined the substituents attached to the quinazoline nucleus and built in additional interactions not present in the initial HTS hit. Optimized compounds activate nucleotide exchange at single-digit micromolar concentrations in vitro. In HeLa cells, these quinazolines increase the levels of RAS-GTP and cause signaling changes in the mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway.
SUBSTITUTED PYRROLOPYRIMIDINES AS HDM2 INHIBITORS
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, (2014/07/08)
The present invention provides substituted pyrrolopyrimidines as described herein or a pharmaceutically acceptable salt or solvate thereof. The representative compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compos
Substituted Imidazopyridines as HDM2 Inhibitors
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Paragraph 0699, (2014/07/08)
The present invention provides substituted imidazopyridines as described herein or a pharmaceutically acceptable salt or solvate thereof. The representative compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compositions comprising the above compounds and potential methods of treating cancer using the same.
2,6,7 SUBSTITUTED PURINES AS HDM2 INHIBITORS
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Page/Page column 68, (2014/08/20)
The present invention provides 2,6,7 substituted purines as described herein or a pharmaceutically acceptable salt thereof. The representative compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compositions comprising the above compounds and potential methods of treating cancer using the same.
2,6,7,8 SUBSTITUTED PURINES AS HDM2 INHIBITORS
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Page/Page column 149; 150, (2014/08/19)
The present invention provides 2,6,7,8 Substituted Purines as described herein or a pharmaceutically acceptable salt thereof. The representative compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compositions compris
