- BICYCLIC COMPOUNDS
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Provided herein are compounds and pharmaceutical compositions comprising said compounds that are useful for treating cancers. Specific cancers include those that are mediated by YAP/TAZ or those that are modulated by the interaction between YAP/TAZ and TEAD.
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Paragraph 00554
(2020/06/01)
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- Asymmetric Synthesis of Fused Polycyclic Indazoles through Aminocatalyzed Aza-Michael Addition/Intramolecular Cyclization
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The first example of an asymmetric aminocatalyzed aza-Michael addition of 1H-indazole derivatives to α,β-unsaturated aldehydes is described. The iminium/enamine cascade process lies at the heart of our strategy, leading to enantioenriched fused polycyclic indazole architectures. Variations on both the α,β-unsaturated aldehydes and the indazole-7-carbaldehyde heterocycles were studied in order to broaden the scope of the transformation in synthetically interesting directions. The fused polycyclic indazoles exhibit fluorescence properties and can undergo synthetic transformations.
- Giardinetti, Maxime,Marrot, Jér?me,Moreau, Xavier,Coeffard, Vincent,Greck, Christine
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p. 6855 - 6861
(2016/08/16)
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- Synthesis and pharmacological evaluation of N-benzyl substituted 4-bromo-2,5-dimethoxyphenethylamines as 5-HT2A/2C partial agonists
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N-Benzyl substitution of phenethylamine 5-HT2A receptor agonists has dramatic effects on binding affinity, receptor selectivity and agonist activity. In this paper we examine how affinity for the 5-HT2A/2C receptors are influenced by N-benzyl substitution of 4-bromo-2,5-dimethoxyphenethylamine derivatives. Special attention is given to the 2′ and 3′-position of the N-benzyl as such compounds are known to be very potent. We found that substitutions in these positions are generally well tolerated. The 2′-position was further examined using a range of substituents to probe the hydrogen bonding requirements for optimal affinity and selectivity, and it was found that small changes in the ligands in this area had a profound effect on their affinities. Furthermore, two ligands that lack a 2′-benzyl substituent were also found to have high affinity contradicting previous held notions. Several high-affinity ligands were identified and assayed for functional activity at the 5-HT2A and 5-HT2C receptor, and they were generally found to be less efficacious agonists than previously reported N-benzyl phenethylamines.
- Hansen, Martin,Jacobsen, Stine Engesgaard,Plunkett, Shane,Liebscher, Gudrun Eckhard,McCorvy, John D.,Br?uner-Osborne, Hans,Kristensen, Jesper Langgaard
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supporting information
p. 3933 - 3937
(2015/01/30)
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- Pyrrolopyrazines as selective spleen tyrosine kinase inhibitors
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We describe the discovery of several pyrrolopyrazines as potent and selective Syk inhibitors and the efforts that eventually led to the desired improvements in physicochemical properties and human whole blood potencies. Ultimately, our mouse model revealed unexpected toxicity that precluded us from further advancing this series.
- Padilla, Fernando,Bhagirath, Niala,Chen, Shaoqing,Chiao, Eric,Goldstein, David M.,Hermann, Johannes C.,Hsu, Jonathan,Kennedy-Smith, Joshua J.,Kuglstatter, Andreas,Liao, Cheng,Liu, Wenjian,Lowrie, Lee E.,Luk, Kin Chun,Lynch, Stephen M.,Menke, John,Niu, Linghao,Owens, Timothy D.,O-Yang, Counde,Railkar, Aruna,Schoenfeld, Ryan C.,Slade, Michelle,Steiner, Sandra,Tan, Yun-Chou,Villase?or, Armando G.,Wang, Ce,Wanner, Jutta,Xie, Wenwei,Xu, Daigen,Zhang, Xiaohu,Zhou, Mingyan,Lucas, Matthew C.
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supporting information
p. 1677 - 1692
(2013/04/10)
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