- Asymmetric Dieckmann Condensation towards Spirocyclic Oxindoles Catalyzed by Amino Acid-Derived Phosphonium Salts
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An asymmetric Dieckmann condensation towards spirocyclic oxindoles and aza-oxindoles catalyzed by amino acid-derived phosphonium salt has been developed, which expanded the applicability of asymmetric phosphonium salt catalysis in the production of 1,3-dicarbonyl compounds. This reaction is distinguished by its mild conditions (?20 °C), low catalyst loading (3–5 mol%), and broad substrate scope (25 examples). Control experiments revealed that both the catalyst‘s phosphonium skeleton and H-bonding site were required. Product transformations and a gram scale experiment were also carried out. (Figure presented.).
- Yu, Longhui,Liu, Jun,Wang, Hongyu,Xu, Lijun,Wu, Yufei,Zheng, Changwu,Zhao, Gang
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supporting information
p. 302 - 306
(2021/11/18)
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- Calcitonin gene-related peptide (CGRP) receptor antagonist treatment of migraine
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Migraine is ranked as the sixth cause of years lost due to disability, with around 1.04 billion migraine sufferers globally. Triptans are considered the standard for acute migraine treatment, but an important number of migraineurs do not respond to them and these drugs are contraindicated in patients with cardiovascular disease. Migraine therapy is currently undergoing tremendous development, i.e., 5-HT1F receptor agonists (ditans), anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies, and small-molecule CGRP receptor antagonists (gepants). Ubrogepant (MK-1620) is a small-molecule, potent and selective CGRP receptor antagonist. In two phase III clinical trials (ACHIEVE I and II), ubrogepant showed, at 2 hours, significant percentages of pain freedom, and absence of the most bothersome symptoms in migraine patients. In a phase III study to assess the long-term (52-week) safety and tolerability, ubrogepant displayed good tolerability, and no signs of hepatic toxicity. In March 2019, the U.S. Food and Drug Administration accepted the new drug application (NDA) for ubrogepant for the acute treatment of migraine.
- Gras
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p. 869 - 879
(2020/01/21)
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- COMPOUNDS
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Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: (I) wherein R1, R2, R3, R4, R5, R6, R8, R9, X, X1, X2, X3, L1 and n are as defined herein. The compounds are inhibitors of adrenomedullin receptor subtype 2 (AM2). Also disclosed are the compounds for use in the treatment of diseases modulated AM2, including proliferative diseases such as cancer; pharmaceutical compositions comprising the compounds; methods for preparing the compounds;and intermediates useful in the preparation of the compounds.
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Page/Page column 324; 326
(2018/12/13)
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- Process for Making CGRP Receptor Antagonists
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The invention encompasses a novel process for making piperidinone carboxamide indane and azainane derivatives, which are CGRP receptor antagonists useful for the treatment of migraine.
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Paragraph 0253; 0254
(2016/06/01)
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- PROCESS FOR MAKING CGRP RECEPTOR ANTAGONISTS
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The disclosure encompasses a novel process for making piperidinone carboxamide indane and azainane derivatives, having less steps and improved yields as compared to previous synthetic methods for making these compounds, which are CGRP receptor antagonists, useful for the treatment of migrane. Conditions for an amide bond formation between an acid and amine include for example reacting the compounds of Formulae B (after salt break) and C with an amide coupling reagent and optionally an additive and an acid and/or a base in a non-reactive solvent.
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Page/Page column 85; 86
(2013/12/03)
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- BIS-QUARTERNARY CINCHONA ALKALOID SALTS AS ASYMMETRIC PHASE TRANSFER CATALYSTS
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The invention is directed to novel bis-quarternary cinchona alkaloid salts and the use of bis-quarternary cinchona alkaloid salts in asymmetric phase transfer catalysis. The present invention is directed to novel bis-quarternary cinchona alkaloid salts an
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Page/Page column 26
(2013/09/26)
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