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Non classé – Page 912 – ChemDigest

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Regioselective Synthesis of Pyrazolyl-pyrimidine Hybrids of Pharmacological Interest

Par / 12 mai 2020 / Non classé

doi.org/10.1055/s-0040-1707948

Synthesis
DOI: 10.1055/s-0040-1707948

The regioselective synthesis of twenty novel [3-substituted 5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl][6-aryl-(2-methylthio)pyrimidin-4-yl]methanones from the cyclocondensation reactions of new 6-aryl-2-(methylthio)pyrimidine-4-carbohydrazides with 4-substituted 1,1,1-trifluorobut-3-en-2-ones is reported. Human acetylcholinesterase (HsAChE) and butyrylcholinesterase (HsBChE) inhibition tests were performed on selected products in order to explore the possible pharmacological applications of these compounds. Two compounds showed significant and selective inhibitory activity for BChE.
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© Georg Thieme Verlag Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

Authors: Camargo, Adriano F.

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Bioisosteric Discovery of NPA101.3, a Second-Generation RET/VEGFR2 Inhibitor Optimized for Single-Agent Polypharmacology

Par / 10 mai 2020 / Non classé

Journal of Medicinal ChemistryDOI: doi.org/10.1021/acs.jmedchem.9b01336%5Bgallery link= »file » columns= »1″]Authors: Marialuisa Moccia†, Brendan Frett‡#, Lingtian Zhang‡, Naga Rajiv Lakkaniga‡, David C. Briggs§, Rakhee Chauhan§, Annalisa Brescia†, Giorgia Federico†, Wei Yan‡, Massimo Santoro†, Neil Q. McDonald§?, Hong-yu Li*‡#, and Francesca Carlomagno*†?feedproxy.google.com/~r/acs/jmcmar/~3/ni_3BKJ20FY/acs.jmedchem.9b01336

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Treating Cancer by Spindle Assembly Checkpoint Abrogation: Discovery of Two Clinical Candidates, BAY 1161909 and BAY 1217389, Targeting MPS1 Kinase

Par / 10 mai 2020 / Non classé

Journal of Medicinal ChemistryDOI: doi.org/10.1021/acs.jmedchem.9b02035%5Bgallery link= »file » columns= »1″]Authors: Volker K. Schulze*†§, Ulrich Klar†, Dirk Kosemund†, Antje M. Wengner†, Gerhard Siemeister†, Detlef Sto¨ckigt†, Roland Neuhaus†, Philip Lienau†, Benjamin Bader†, Stefan Prechtl†, Simon J. Holton†, Hans Briem†, Tobias Marquardt‡, Hartmut Schirok‡, Rolf Jautelat‡, Rolf Bohlmann†, Duy Nguyen†, Amaury E. Ferna´ndez-Montalva´n†?, Ulf Bo¨mer†, Uwe Eberspaecher†, Michael Bru¨ning†, Olaf Do¨hr†, Marian Raschke†, Bertolt Kreft†, Dominik Mumberg†, Karl Ziegelbauer†, Michael Brands†, Franz von Nussbaum†, and Marcus Koppitz*†§http://feedproxy.google.com/~r/acs/jmcmar/~3/rpYQsW7rYTk/acs.jmedchem.9b02035

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Discovery of Peptide Boronate Derivatives as Histone Deacetylase and Proteasome Dual Inhibitors for Overcoming Bortezomib Resistance of Multiple Myeloma

Par / 10 mai 2020 / Non classé

Journal of Medicinal ChemistryDOI: doi.org/10.1021/acs.jmedchem.9b02161%5Bgallery link= »file » columns= »1″]Authors: Yi Zhou†, Xiaoting Liu‡, Junxin Xue†, Lulu Liu†, Tao Liang†, Wen Li†, Xinying Yang‡, Xuben Hou†, and Hao Fang*†http://feedproxy.google.com/~r/acs/jmcmar/~3/IYxMtnQAPTM/acs.jmedchem.9b02161

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Continuous-Flow Synthesis of (–)-Oseltamivir Phosphate (Tamiflu)

Par / 20 mai 2020 / flow_chemi​stry, Non classé

SynlettDOI: 10.1055/s-0039-1690878Herein the anti-influenza drug (–)-oseltamivir phosphate is prepared in continuous flow from ethyl shikimate with 54% overall yield over nine steps and total residence time of 3.5 min from the individual steps. Although the procedure involved intermediate isolation, the dangerous azide chemistry and intermediates involved were elegantly handled in situ. It is the first continuous-flow process for (–)-oseltamivir phosphate involving azide chemistry and (–)-shikimic acid as precursor.[…]© Georg Thieme Verlag Stuttgart · New YorkArticle in Thieme eJournals:Table of contents  |  Abstract  |  Full text

Authors: Sagandira, Cloudius R.doi.org/10.1055/s-0039-1690878

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Direct Phosphonylation of N-Carbamate-tetrahydroisoquinoline by Convergent Paired Electrolysis

Par / 10 mai 2020 / Non classé

SynlettDOI: 10.1055/s-0039-1690899Mild experimental conditions for a direct phosphonylation of an easily cleavable N-carbamate-tetrahydroisoquinoline have been described under constant current electrolysis. The developed electrochemical process allowed to prepare α-aminophosphonates in moderate to good yields. On the basis of the experimental results, a mechanism proceeding through a convergent paired electrochemical process was enabled to be postulated.[…]© Georg Thieme Verlag Stuttgart · New YorkArticle in Thieme eJournals:Table of contents  |  Abstract  |  Full text

Authors: Ollivier,

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Palladium-Catalyzed Silylation of Aryl Chlorides with Bulky Dialkoxydisilanes

Par / 10 mai 2020 / Non classé

SynlettDOI: 10.1055/s-0039-1690877Arylsilanes bearing a bulky alkoxy group on the silicon were synthesized from aryl chlorides and dialkoxydisilanes under reaction conditions utilizing SingaCycle-A3 as a palladium precatalyst and lithium benzoate in wet DMA. This report proposes the first direct and catalytic method for introducing tert-butoxy- or 1-adamantyloxysilyl groups onto various aryl moieties through the silylation reaction.[…]© Georg Thieme Verlag Stuttgart · New YorkArticle in Thieme eJournals:Table of contents  |  Abstract  |  Full text

Authors: Fukui,

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α-Fluorination of Nitrobenzenes and Nitropyridines via Vicarious Nucleophilic Substitution of Hydrogen

Par / 10 mai 2020 / Non classé

SynlettDOI: 10.1055/s-0039-1690862A highly selective C–H functionalization of nitrobenzenes and nitropyridines is reported using tandem vicarious nucleophilic substitution (VNS) chemistry with electrophilic fluorination using Selectfluor®. The process generates tertiary benzylic fluorides in good yield under simple, mild conditions and short reaction times.[…]© Georg Thieme Verlag Stuttgart · New YorkArticle in Thieme eJournals:Table of contents  |  Abstract  |  Full text

Authors: Al-Mkhaizim, Fayez Y.doi.org/10.1055/s-0039-1690862

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Metal-Free Addition of Boronic Acids to Silylnitronates

Par / 10 mai 2020 / Non classé

SynlettDOI: 10.1055/s-0039-1690845We report for the first time a metal-free addition of boronic acids to silylnitronates to afford oxime derivatives through aryl transfer on the carbon nitrogen double bond. A reaction mechanism has been proposed in relation with a DFT study on the key aryl transfer. This arylation process is effective for cycloalkenyl nitro derivatives leading to oximes that may be oxidatively converted into 3-arylisoxazole derivatives.[…]© Georg Thieme Verlag Stuttgart · New YorkArticle in Thieme eJournals:Table of contents  |  Abstract  |  Full text

Authors: Kerim, Mansour Doléhttps://doi.org/10.1055/s-0039-1690845

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Practical Approach for the Preparation of α-Keto Amides by Direct Aminocarbonylation of Carboxylic Esters with a Carbamoylsilane

Par / 10 mai 2020 / Non classé

SynlettDOI: 10.1055/s-0039-1691737A novel and practical method has been developed for the preparation of α-keto amides by a catalyst-free aminocarbonylation of carboxylic esters with N,N-dimethylcarbamoyl(trimethyl)silane under neutral conditions. A new protocol for the synthesis of vicinal tricarbonyl compounds was also developed by using this method. In the case of diesters, only one ester group reacted selectively with 1.2 equivalents of the carbamoylsilane, leading to the formation of a single α-keto amide. The reaction was suitable for aryl, hetaryl, or open-chain esters containing strongly electron-withdrawing groups.[…]© Georg Thieme Verlag Stuttgart · New YorkArticle in Thieme eJournals:Table of contents  |  Abstract  |  Full text

Authors: Han,

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Iodine-Based Reagents in Oxidative Amination and Oxygenation

Par / 10 mai 2020 / Non classé

SynlettDOI: 10.1055/s-0039-1690827In this Account, we provide an overview of our recent advances in oxidative transformations that enable the introduction of nitrogen and oxygen functionalities into organic molecules by taking advantage of the unique characteristics of iodine-based reagents, such as hypervalency, soft Lewis acidity, high leaving ability, and radical reactivity. We also report on the development of new types of hypervalent iodine reagents containing a transferable nitrogen functional group with the objective of preparing primary amines, which is described in the latter part of this Account.1 Introduction2 Decarboxylative Functionalization of β,γ-Unsaturated Carboxylic Acids3 Decarboxylative Functionalization at Tertiary Carbon Centers4 C–H Bond Functionalization at Tertiary Carbon Centers5 Intramolecular C–H Amination of Sulfamate Esters and N-Alkylsulfamides6 Oxidative Amination with Hypervalent Iodine Reagents Containing Transferable Nitrogen Functional Groups7 Summary and Outlook[…]© Georg Thieme Verlag Stuttgart · New YorkArticle in Thieme eJournals:Table of contents  |  Abstract  |  Full text

Authors: Kiyokawa,

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A Frustrated Lewis Pair Solution to a Frustrating Problem: Mono-Selective Functionalization of C–F Bonds in Di- and Trifluoromethyl Groups

Par / 10 mai 2020 / Non classé

SynlettDOI: 10.1055/s-0039-1690811Polyfluoromethyl groups generally suffer from over-reaction, where multiple C–F bonds are uncontrollably functionalized. The use of a frustrated Lewis pair (FLP)-mediated C–F bond activation permits selective monodefluorination through base capture of intermediate fluorocarbocations. FLP-mediated C–F bond activation can be applied to aromatic, heteroaromatic, or nonaromatic difluoro and trifluoromethyl groups to generate selectively fluoride-substituted phosphonium and pyridinium salts. These salts can be further functionalized by Wittig coupling, nucleophilic substitution, photoredox alkylation, nucleophilic transfer, or hydrogenation reactions to install a range of functional groups into the activated C–F position.1 Introduction2 Frustrated Lewis Pair C–F Activation3 Conclusion[…]© Georg Thieme Verlag Stuttgart · New YorkArticle in Thieme eJournals:Table of contents  |  Abstract  |  Full text

Authors: Gupta,

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Brominated β-Alkoxyvinyl Trihalomethyl Ketones as Promising Synthons in Heterocyclic Synthesis

Par / 10 mai 2020 / Non classé

SynthesisDOI: 10.1055/s-0039-16908905-Bromo- and 5,5-dibromo-1,1,1-trihalo-4-methoxypent-3-en-2-ones (brominated enones) have proven to be attractive building blocks for the construction of heterocyclic and polyheterocyclic compounds bearing a trihalomethyl moiety through interesting cyclocondensation, alkylation, and cycloaddition reactions. This review compiles all of the reactions conducted with these brominated enones since they were first disclosed in 2001.1 Introduction2 Synthesis and Initial Applications3 Synthesis Using First-Generation Intermediates4 Synthesis Using Second-Generation Intermediates5 Synthesis Using Third-Generation Intermediates6 Conclusions[…]© Georg Thieme Verlag Stuttgart · New YorkArticle in Thieme eJournals:Table of contents  |  Abstract  |  Full text

Authors: Mittersteiner,

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Recent Advances in the Synthesis of Enantiomerically Enriched Diaryl, Aryl Heteroaryl, and Diheteroaryl Alcohols through Addition of Organometallic Reagents to Carbonyl Compounds

Par / 10 mai 2020 / Non classé

SynthesisDOI: 10.1055/s-0039-1690847Enantiomerically enriched diaryl, aryl heteroaryl, and dihetero­aryl alcohols are an important family of compounds known for their biological properties. Moreover, these molecules are highly privileged scaffolds used as building blocks for the synthesis of pharmaceutically relevant products. This short review provides background on the enantioselective arylation and heteroarylation of carbonyl compounds, as well as, the most significant improvements in this field with special emphasis on the application of organometallic reagents.1 Introduction2 Background on the Enantioselective Synthesis of Diaryl, Aryl Heteroaryl, and Diheteroaryl Alcohols3 Organozinc Reagents4 Organolithium Reagents5 Grignard Reagents6 Organoaluminum Reagents7 Organotitanium Reagents8 Organobismuth Reagents9 Miscellaneous10 Conclusion[…]© Georg Thieme Verlag Stuttgart · New YorkArticle in Thieme eJournals:Table of contents  |  Abstract  |  Full text

Authors: Teixeira, Wystan K. O.doi.org/10.1055/s-0039-1690847

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Synthesis of Fused Pyridine Carboxylates by Reaction of β-Alkoxyvinyl Glyoxylates with Amino Heterocycles

Par / 10 mai 2020 / Non classé

SynthesisDOI: 10.1055/s-0039-1707987An efficient approach to the preparation of pyridine carboxylates fused with 5- or 6-membered heteroaromatic rings is described. The method relied on the Combes-type condensation of the low-molecular­-weight β-alkoxyvinyl glyoxylates as CCC bis-electrophiles and with heteroaromatic amines as NCC binucleophiles. In most experiments­, β-alkoxyvinyl glyoxylates without additional substituent at the β position led to the corresponding α-pyridine carboxylates (67–87% yield). In the case of β-methyl-substituted derivative, γ-pyridine carboxylates were obtained in 84–99% yield. It was found that regio­selectivity of the condensation could be efficiently tuned by changing conditions, such as solvents and acidic additives (HOAc, DMSO or HCl–1,4-dioxane).[…]© Georg Thieme Verlag Stuttgart · New YorkArticle in Thieme eJournals:Table of contents  |  Abstract  |  Full text

Authors: Stepaniuk, Oleksandr O.doi.org/10.1055/s-0039-1707987

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Recent Advances in Photocatalytic Decarboxylative Coupling Reactions in Medicinal Chemistry

Par / 10 mai 2020 / Non classé

SynthesisDOI: 10.1055/s-0039-1690843This review covers recent advances in decarboxylative photocatalysis applicable to the medicinal chemist. The review is not intended to be exhaustive, but instead is focussed on transformations that could be useful in the synthesis of drug-like compounds in order to highlight the utility of this methodology in the development of new pharmaceutical candidates.1 Introduction2 C–C Bond Formation3 C–N and C–O Bond Formation4 Fluorination and Trifluoromethylation5 Hydrodecarboxylation6 Protein Functionalisation7 Conclusion[…]© Georg Thieme Verlag Stuttgart · New YorkArticle in Thieme eJournals:Table of contents  |  Abstract  |  Full text

Authors: McMurray,

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