Applications of Deuterium in Medicinal Chemistry

Journal of Medicinal Chemistry, Год журнала: 2019, Номер 62(11), С. 5276 - 5297

Опубликована: Янв. 14, 2019

The use of deuteration in medicinal chemistry has exploded the past years, and FDA recently approved first deuterium-labeled drug. Precision goes beyond pure simple amelioration pharmacokinetic parameters a drug might provide an opportunity when facing problems terms metabolism-mediated toxicity, interactions, low bioactivation. deuterium is even broader, offering to lower degree epimerization, reduce dose coadministered boosters, discover compounds where basis for mechanism action. Nevertheless, designing, synthesizing, developing successful deuterated far from straightforward, translation concept practice often unpredictable. This Perspective provides overview recent developments deuteration, with focus on clinical candidates, highlights both opportunities challenges this strategy.

Язык: Английский

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Technological Innovations in Photochemistry for Organic Synthesis: Flow Chemistry, High-Throughput Experimentation, Scale-up, and Photoelectrochemistry

Chemical Reviews, Год журнала: 2021, Номер 122(2), С. 2752 - 2906

Опубликована: Авг. 10, 2021

Photoinduced chemical transformations have received in recent years a tremendous amount of attention, providing plethora opportunities to synthetic organic chemists. However, performing photochemical transformation can be quite challenge because various issues related the delivery photons. These challenges barred widespread adoption steps industry. past decade, several technological innovations led more reproducible, selective, and scalable photoinduced reactions. Herein, we provide comprehensive overview these exciting advances, including flow chemistry, high-throughput experimentation, reactor design scale-up, combination photo- electro-chemistry.

Язык: Английский

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Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Chemical Reviews, Год журнала: 2022, Номер 122(6), С. 6634 - 6718

Опубликована: Фев. 18, 2022

Organic compounds labeled with hydrogen isotopes play a crucial role in numerous areas, from materials science to medicinal chemistry. Indeed, while the replacement of by deuterium gives rise improved absorption, distribution, metabolism, and excretion (ADME) properties drugs enables preparation internal standards for analytical mass spectrometry, use tritium-labeled is key technique all along drug discovery development pharmaceutical industry. For these reasons, interest new methodologies isotopic enrichment organic molecules extent their applications are equally rising. In this regard, Review intends comprehensively discuss developments area over last years (2017–2021). Notably, besides fundamental isotope exchange (HIE) reactions isotopically analogues common reagents, plethora reductive dehalogenative deuteration techniques other transformations incorporation emerging now part labeling toolkit.

Язык: Английский

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Achieving Site-Selectivity for C–H Activation Processes Based on Distance and Geometry: A Carpenter’s Approach

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(24), С. 10571 - 10591

Опубликована: Май 21, 2020

The ability to differentiate between highly similar C–H bonds in a given molecule remains fundamental challenge organic chemistry. In particular, the lack of sufficient steric and electronic differences located distal functional groups has prevented development site-selective catalysts with broad scope. An emerging approach circumvent this obstacle is utilize distance target bond coordinating group, along geometry cyclic transition state directed activation, as core molecular recognition parameters multiple bonds. Perspective, we discuss advent recent advances concept. We cover wide range transition-metal-catalyzed, template-directed remote activation reactions alcohols, carboxylic acids, sulfonates, phosphonates, amines. Additionally, review eminent examples which take advantage non-covalent interactions achieve regiocontrol. Continued advancement distance- geometry-based differentiation for regioselective functionalization may lead ultimate realization editing: freedom modify molecules at any site, order.

Язык: Английский

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Photocatalysis in the Life Science Industry

Chemical Reviews, Год журнала: 2021, Номер 122(2), С. 2907 - 2980

Опубликована: Сен. 24, 2021

In the pursuit of new pharmaceuticals and agrochemicals, chemists in life science industry require access to mild robust synthetic methodologies systematically modify chemical structures, explore novel space, enable efficient synthesis. this context, photocatalysis has emerged as a powerful technology for synthesis complex often highly functionalized molecules. This Review aims summarize published contributions field from industry, including research industrial-academic partnerships. An overview developed strategic applications synthesis, peptide functionalization, isotope labeling, both DNA-encoded traditional library is provided, along with summary state-of-the-art photoreactor effective upscaling photocatalytic reactions.

Язык: Английский

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Deuterium in drug discovery: progress, opportunities and challenges

Nature Reviews Drug Discovery, Год журнала: 2023, Номер 22(7), С. 562 - 584

Опубликована: Июнь 5, 2023

Язык: Английский

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Deoxygenative Deuteration of Carboxylic Acids with D₂O

Angewandte Chemie International Edition, Год журнала: 2018, Номер 58(1), С. 312 - 316

Опубликована: Окт. 23, 2018

We report a general, practical, and scalable means of preparing deuterated aldehydes from aromatic aliphatic carboxylic acids with D2 O as an inexpensive deuterium source. The use Ph3 P O-atom transfer reagent can facilitate the deoxygenation acids, while Ph2 POEt is better for acids. highly precise complex makes this protocol promising late-stage deoxygenative deuteration natural product derivatives pharmaceutical compounds.

Язык: Английский

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A general carbonyl alkylative amination for tertiary amine synthesis

Nature, Год журнала: 2020, Номер 581(7809), С. 415 - 420

Опубликована: Апрель 8, 2020

Язык: Английский

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Tritiation of aryl thianthrenium salts with a molecular palladium catalyst

Nature, Год журнала: 2021, Номер 600(7889), С. 444 - 449

Опубликована: Дек. 15, 2021

Abstract Tritium labelling is a critical tool for investigating the pharmacokinetic and pharmacodynamic properties of drugs, autoradiography, receptor binding occupancy studies 1 . gas preferred source tritium preparation labelled molecules because it available in high isotopic purity 2 The introduction labels from commonly achieved by heterogeneous transition-metal-catalysed tritiation aryl (pseudo)halides. However, catalysts such as palladium supported on carbon operate through reaction mechanism that also results reduction other functional groups are prominently featured pharmaceuticals 3 Homogeneous can react chemoselectively with (pseudo)halides but have not been used hydrogenolysis reactions because, after required oxidative addition, they cannot split dihydrogen 4 Here we report homogenous well defined, molecular catalyst. We show how thianthrene leaving group—which be introduced selectively into late-stage C–H functionalization 5 —differs its coordinating ability to relevant palladium(II) conventional enable previously unrealized catalysis dihydrogen. This distinct reactivity combined chemoselectivity defined catalyst enables small-molecule contain functionality may otherwise tolerated catalysts. does require an inert atmosphere or dry conditions therefore practical robust execute, could immediate impact discovery development pharmaceuticals.

Язык: Английский

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Photoinduced gold-catalyzed divergent dechloroalkylation of gem-dichloroalkanes

Nature Catalysis, Год журнала: 2022, Номер 5(12), С. 1098 - 1109

Опубликована: Дек. 15, 2022

Язык: Английский

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