Energy transfer photocatalysis: exciting modes of reactivity

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(3), P. 1068 - 1089

Published: Jan. 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.

Language: Английский

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Oxetanes in Drug Discovery Campaigns

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(18), P. 12697 - 12709

Published: Sept. 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.

Language: Английский

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

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(10), P. 7788 - 7824

Published: May 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.

Language: 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, Journal Year: 2024, Volume and Issue: 146(30), P. 21069 - 21077

Published: July 16, 2024

The direct construction of bioisosteric compounds enriched in C

Language: Английский

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

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 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.

Language: Английский

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Direct Bioisostere Replacement Enabled by Metallaphotoredox Deoxydifluoromethylation

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(8), P. 5067 - 5073

Published: Feb. 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.

Language: Английский

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

Organic Letters, Journal Year: 2024, Volume and Issue: 26(3), P. 713 - 718

Published: Jan. 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.

Language: Английский

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

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 13121 - 13121

Published: Dec. 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.

Language: 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, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 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

Language: Английский

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AI for organic and polymer synthesis

Science China Chemistry, Journal Year: 2024, Volume and Issue: 67(8), P. 2461 - 2496

Published: June 26, 2024

Language: Английский

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