Energy transfer photocatalysis: exciting modes of reactivity

Chemical Society Reviews, Год журнала: 2024, Номер 53(3), С. 1068 - 1089

Опубликована: Янв. 1, 2024

Leveraging light energy to expose the ‘dark’ reactive states describes whole essence of triplet–triplet transfer. This offers an impressive opportunity conduct a multitude diverse reactions and access sought-after molecular motifs.

Язык: Английский

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Oxetanes in Drug Discovery Campaigns

Journal of Medicinal Chemistry, Год журнала: 2023, Номер 66(18), С. 12697 - 12709

Опубликована: Сен. 7, 2023

The oxetane ring is an emergent, underexplored motif in drug discovery that shows attractive properties such as low molecular weight, high polarity, and marked three-dimensionality. Oxetanes have garnered further interest isosteres of carbonyl groups tools to fine-tune physicochemical compounds pKa, LogD, aqueous solubility, metabolic clearance. This perspective highlights recent applications motifs campaigns (2017–2022), with emphasis on the effect medicinally relevant building blocks used incorporate ring. Based this analysis, we provide overview potential benefits appending a compound, well pitfalls, challenges, future directions.

Язык: Английский

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Triazoles in Medicinal Chemistry: Physicochemical Properties, Bioisosterism, and Application

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(10), С. 7788 - 7824

Опубликована: Май 3, 2024

Triazole demonstrates distinctive physicochemical properties, characterized by weak basicity, various dipole moments, and significant dual hydrogen bond acceptor donor capabilities. These features are poised to play a pivotal role in drug–target interactions. The inherent polarity of triazole contributes its lower logP, suggesting the potential improvement water solubility. metabolic stability adds additional value drug discovery. Moreover, metal-binding capacity nitrogen atom lone pair electrons has broad applications development metal chelators antifungal agents. This Perspective aims underscore unique attributes application. A comparative analysis involving isomers other heterocycles provides guiding insights for subsequent design triazoles, with hope offering valuable considerations designing medicinal chemistry.

Язык: Английский

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Catalytic Asymmetric Construction of Chiral Polysubstituted 3-Azabicyclo[3.1.1]heptanes by Copper-Catalyzed Stereoselective Formal [4π+2σ] Cycloaddition

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(30), С. 21069 - 21077

Опубликована: Июль 16, 2024

The direct construction of bioisosteric compounds enriched in C

Язык: Английский

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Direct Bioisostere Replacement Enabled by Metallaphotoredox Deoxydifluoromethylation

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(8), С. 5067 - 5073

Опубликована: Фев. 16, 2024

The replacement of a functional group with its corresponding bioisostere is widely employed tactic during drug discovery campaigns that allows medicinal chemists to improve the ADME properties candidates while maintaining potency. However, incorporation bioisosteres typically requires lengthy de novo resynthesis potential candidates, which represents bottleneck in their broader evaluation. An alternative would be directly convert into at late stage. Herein, we report realization this approach through conversion aliphatic alcohols difluoromethylated analogues via merger benzoxazolium-mediated deoxygenation and copper-mediated C(sp3)–CF2H bond formation. utility method showcased variety complex compounds.

Язык: Английский

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Copper-Catalyzed Enantioselective [4π + 2σ] Cycloaddition of Bicyclobutanes with Nitrones

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Сен. 25, 2024

The selective construction of bridged bicyclic scaffolds has garnered increasing attention because their extensive use as saturated bioisosteres arene in pharmaceutical industry. However, sharp contrast to racemic counterparts, assembling chiral structures an enantioselective and regioselective manner remains challenging. Herein, we describe our protocol for constructing 2-oxa-3-azabicyclo[3.1.1]heptanes (BCHeps) by [4π + 2σ] cycloadditions bicyclo[1.1.0]butanes (BCBs) nitrones taking advantage a copper(II) complex Lewis acid catalyst. This method features mild conditions, good functional group tolerance, high yield (up 99%), excellent enantioselectivity 99% ee). Density theory (DFT) calculation elucidates the origin reaction's mechanism BCB activation Cu(II) complex.

Язык: Английский

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Visible-Light-Induced Decarboxylative Aminosulfonylation of (Hetero)aryl Carboxylic Oxime Esters

Organic Letters, Год журнала: 2024, Номер 26(3), С. 713 - 718

Опубликована: Янв. 12, 2024

Sulfonamides are important structures in pharmaceuticals, agrochemicals, and organocatalysts, yet the rapid benign synthesis of these compounds is still a great challenge. Herein we report photoinduced method for synthesizing sulfonamides from (hetero)aryl carboxylic acid oxime esters. This reaction proceeds via one-pot cascade radical–radical cross-coupling by energy-transfer-mediated photocatalysis. A wide substrate scope including substrates late-stage modification pharmaceutical molecular entities reveal its generality.

Язык: Английский

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Late-stage meta-C–H alkylation of pharmaceuticals to modulate biological properties and expedite molecular optimisation in a single step

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 18, 2024

Catalysed C-H activation has emerged as a transformative platform for molecular synthesis and provides new opportunities in drug discovery by late-stage functionalisation (LSF) of complex molecules. Notably, small aliphatic motifs have gained significant interest medicinal chemistry their beneficial properties applications sp

Язык: Английский

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AI for organic and polymer synthesis

Science China Chemistry, Год журнала: 2024, Номер 67(8), С. 2461 - 2496

Опубликована: Июнь 26, 2024

Язык: Английский

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Overcoming Challenges in Small-Molecule Drug Bioavailability: A Review of Key Factors and Approaches

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 13121 - 13121

Опубликована: Дек. 6, 2024

The bioavailability of small-molecule drugs remains a critical challenge in pharmaceutical development, significantly impacting therapeutic efficacy and commercial viability. This review synthesizes recent advances understanding overcoming limitations, focusing on key physicochemical biological factors influencing drug absorption distribution. We examine cutting-edge strategies for enhancing bioavailability, including innovative formulation approaches, rational structural modifications, the application artificial intelligence design. integration nanotechnology, 3D printing, stimuli-responsive delivery systems are highlighted as promising avenues improving delivery. discuss importance holistic, multidisciplinary approach to optimization, emphasizing early-stage consideration ADME properties need patient-centric also explores emerging technologies such CRISPR-Cas9-mediated personalization microbiome modulation tailored enhancement. Finally, we outline future research directions, advanced predictive modeling, barriers, addressing challenges modalities. By elucidating complex interplay affecting this aims guide efforts developing more effective accessible therapeutics.

Язык: Английский

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