- Scalable, Telescoped Hydrogenolysis-Enzymatic Decarboxylation Process for the Asymmetric Synthesis of (R)-α-Heteroaryl Propionic Acids
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Enantiopure α-aryl propionic acids are useful building blocks for pharmaceutical research and can be accessed enzymatically using arylmalonate decarboxylases (AMDases) from the corresponding malonic acids. However, the intrinsic instability of malonic acids is a major drawback to this approach in which spontaneous decarboxylation can occur, subsequently eroding enantioselectivity and giving rise to racemic products. This was particularly evident for a panel of N-heterocyclic propionic acids that we wished to access using the approach. Herein, we describe a process to overcome the spontaneous decarboxylation problem in which hydrogenolysis of the corresponding dibenzyl malonates was performed in a biphasic toluene-basic aqueous buffer mixture and telescoped into the subsequent AMDase step. This procedure enabled compounds to be accessed in high enantioselectivities and was successfully demonstrated on 120 g with high yield (76%) and ee (98%).
- Blakemore, Caroline A.,France, Scott P.,Samp, Lacey,Nason, Deane M.,Yang, Eddie,Howard, Roger M.,Coffman, Karen J.,Yang, Qingyi,Smith, Aaron C.,Evrard, Edelweiss,Li, Wei,Dai, Linlin,Yang, Lixia,Chen, Zhiguang,Zhang, Qingli,He, Fangyan,Zhang, Jiesen
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supporting information
p. 421 - 426
(2020/11/12)
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- CDK kinase inhibitors
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The present invention belongs to the technical field of medicine, and particularly relates to a CDK kinase inhibitor represented by a general formula (I), a pharmaceutically acceptable salt of the CDK kinase inhibitor, an ester of the CDK kinase inhibitor, a solvate of the CDK kinase inhibitor and stereoisomers of the CDK kinase inhibitor, the pharmaceutically acceptable salt, the ester and the solvate, wherein R1, R2, R3, R4, R5 and n are defined in the specification. The present invention further relates to preparation methods of the compounds, pharmaceutical formulations containing the compounds, pharmaceutical compositions containing the compounds, and applications of the compound, the pharmaceutically acceptable salt, the ester, the solvate and the stereoisomers in preparation of treatment and/or preparation of CDK kinase-mediated cancer associated diseases. The formula (I) is defined in the specification.
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Paragraph 0213-0216
(2017/08/02)
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- KINASE INHIBITOR AND USE THEREOF
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The invention relates to a CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers; a pharmaceutical formulation, pharmaceutical composition and kit comprising said CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers, and use of said CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers. For example, the compounds of the invention are useful for reducing or inhibiting the activity of CDK4/6 kinase in a cell, and/or treating and/or preventing a cancer-related disease mediated by CDK4/6 kinase.
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Paragraph 0167; 0168
(2016/11/21)
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- N-LINKED HYDROXAMIC ACID DERIVATIVES USEFUL AS ANTIBACTERIAL AGENTS
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The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors, and more specifically their use to treat bacterial infections. Formula (I).
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Page/Page column 116-117
(2011/07/07)
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- NEW 3-([1,2,4]TRIAZOLO[4,3-A]PYRIDIN-7-YL)BENZAMIDE DERIVATIVES
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This invention is directed to new inhibitors of the p38 mitogen-activated protein kinase having the general formula (I) to processes for their preparation; to pharmaceutical compositions comprising them; and to their use in therapy.
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Page/Page column 43-44
(2008/12/07)
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