FDA‐approved drugs featuring macrocycles or medium‐sized rings

Archiv der Pharmazie, Journal Year: 2025, Volume and Issue: 358(1)

Published: Jan. 1, 2025

Abstract Macrocycles or medium‐sized rings offer diverse functionality and stereochemical complexity in a well‐organized ring structure, allowing them to fulfill various biochemical functions, resulting high affinity selectivity for protein targets, while preserving sufficient bioavailability reach intracellular compartments. These features have made macrocycles attractive candidates organic synthesis drug discovery. Since the 20th century, more than three‐score macrocyclic drugs, including radiopharmaceuticals, been approved by US Food Drug Administration (FDA) treating bacterial viral infections, cancer, obesity, immunosuppression, inflammatory, neurological disorders, managing cardiovascular diseases, diabetes, more. This review presents 17 FDA‐approved drugs during past 5 years, highlighting their importance critical role modern therapeutics, innovative synthetic approaches construction of these macrocycles.

Language: Английский

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Recent advances on electrochemical generation of sulfonyl radical triggered cyclization of alkene/alkynes

Tetrahedron, Journal Year: 2025, Volume and Issue: 173, P. 134467 - 134467

Published: Jan. 12, 2025

Language: Английский

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What Do We Know About Per- or Polyfluoroalkyl Substances (PFASs)? Issues, Challenges, Regulations, and Possible Alternatives

Macromolecules, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Per- or polyfluoroalkyl substances (PFASs) are man-made compounds involved in compositions of many industrial processes and consumer products. They categorized into two main families based on their molar mass: though low mass products (<1000 Da) toxic, mobile, bioaccumulable, cross the human membranes, others much higher masses, e.g., fluorinated macromolecules especially fluoropolymers, safe reliable, do not face such concerns, membranes (hence, they regarded as Polymers Low Concern), applications including medical high-value-added materials devices. Because former family has led to a severe global contamination, recent regulating agencies Europe (REACH) USA (EPA) have aimed at restricting fluorochemicals. Recently, consultations from affected organisms industries more than 5600 answers comments. This review supplies an update overall situation PFASs, limitations, regulations, end life, degradations, possible alternatives.

Language: Английский

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Synthesis of fluorine-containing bicyclo[4.1.1]octenes via photocatalyzed defluorinative (4+3) annulation of bicyclo[1.1.0]butanes with gem-difluoroalkenes

Chemical Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 13, 2024

This manuscript presents a photoredox-catalyzed defluorinative (4 + 3) annulation of bicyclo[1.1.0]butanes with gem -difluoroalkenes, providing practical and straightforward access to the fluorine-containing bicyclo[4.1.1]octenes.

Language: Английский

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The influence of fluorine spin-diffusion on ¹³C solid-state NMR line shapes of CF₃ groups

Physical Chemistry Chemical Physics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Indirect spin-spin couplings ("J-couplings") lead to well-known multiplet patterns in nuclear magnetic resonance (NMR) spectra that are also observable non-decoupled solid-state NMR spectra, if the J-coupling constant exceeds linewidth. Such J-multiplet line shapes solid state might however be affected by spin diffusion (SD) on passive nuclei. When SD rate is fast compared constant, resolution can lost due a so-called "self-decoupling" mechanism as has been already reported context of decoupling and for proton adamantane. We herein report influence 19F 13C-detected small organic molecule bearing trifluoromethyl group. The target compound chiral α-(trifluoromethyl)lactic acid (TFLA). Enantiopure phases ((R) or (S), respectively) TFLA composed homochiral dimers whereas racemic phase consists heterochiral state. Despite their structural similarity, 13C CF3 group cross-polarization recorded at slow medium magic-angle spinning (MAS) frequencies - range between 14.0 kHz 60.0 differ substantially. By combining experimental observations, analytical calculations based Bloch-McConnell equations, numerical spin-dynamics simulations, we demonstrate differences enantiopure TFLA-phases significantly affect respective spectral shapes. Slowing down increasing MAS frequency restores quartet shape both TFLA.

Language: Английский

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Nickel-Catalyzed Reductive Arylation of gem-Bromofluorocyclopropanes To Construct Monofluorinated Cyclopropane Derivatives

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

A nickel-catalyzed reductive cross-coupling of gem-bromofluorocyclopropanes with aryl bromides for the synthesis monofluorinated cyclopropane derivatives is reported. Different from cleavage route ring reported by previous works, this catalytic system shows excellent regioselectivity control cyclic selectivity, giving as major product. This transformation demonstrates mild conditions, high efficiency, a broad substrate scope, and good functional group compatibility, providing facile method diversified cyclopropane-containing drugs bioactive molecules.

Language: Английский

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Discovery of novel quinazoline derivatives containing trifluoromethyl against cell proliferation by targeting werner helicase

Molecular Diversity, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Language: Английский

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From fluorine’s position in the periodic table to PFAS environmental issues

Comptes Rendus Chimie, Journal Year: 2025, Volume and Issue: 28(G1), P. 423 - 438

Published: April 16, 2025

PFASs have become a global pollution issue. These anthropogenic and unusually stable chemicals been in use since the 1940s. Thousands of them, whether molecular or polymeric, developed are found innumerable industrial processes consumer products. Multiple air water pathways ensure their dissemination when released into environment. They can adhere to rock sediment, concrete, tarmac, asphalt. Humans, animals, plants thus exposed through air, dust, soil, diet, drinking water, wastewater. Some identified as very persistent environment, bioaccumulative, toxic by public health authorities. This review emphasizes that specific outstanding properties C–F bond derive directly from fluorine’s position periodic table. Fluorinated surfactants also capacity form large, exceptionally sturdy supramolecular self-assemblies aqueous solutions, on solid surfaces at liquid interfaces. behavior may impact fate PFAS pollutants well remediation procedures, fact has so far barely recognized. Finding alternatives fluorinated fluoropolymers deliver comparably high performances while reducing environmental biological be extremely challenging. The essential concept distinguishes uses for which, current state, hardly find any replacement product capable matching demanded those which lesser performance is sufficient attainable otherwise, not speak downright futile. need discerning, eco-responsible accentuated if we want continue benefit unmatchable performances.

Language: Английский

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CHIRAL, FLUORINE-CONTAINING PHARMACEUTICALS

Ukrainian Chemistry Journal, Journal Year: 2025, Volume and Issue: 91(2), P. 55 - 90

Published: March 25, 2025

Fluorine is a key element in drug design due to its ability enhance metabolic stability, binding affinity, and bioavailability. Fluorine’s properties lead more stable drugs with longer half-lives, reducing dosing frequency improving patient compliance. Its small size high electronegativity also improve resulting effective treatments lower doses. For example, fluorine increases compound’s cross cell memb­ranes. This article highlights advancements chiral, fluorine-containing pharmaceuticals introduced over the past five years, focusing on their synthesis, therapeutic benefits, mechanisms of action, impact efficacy safety. Chiral molecules, essential development, exist two enantiomeric forms distinct biological activities. Synthesizing involves techniques like asymmetric synthesis produce pure enantiomers, increased potency, selectivity, reduced side effects. Understanding action provides valuable insights into Reviewing recently FDA-approved chiral offers chemistry development future innovations. Recent FDA approvals highlight significance various areas, enabling targeted treatments. Analyzing these reveals trends shaping development’s future. The addresses need for research self-disproportionation enantiomers (SDE) fluorinated compounds concerns about excessive levels. SDE can affect pharmaceutical product purity. Research ensures quality. Additionally, fluorine’s widespread use raises environmental health concerns, necessitating studies long-term effects mitigation strategies.

Language: Английский

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Radical Acylfluoroalkylation of 1,3-Enynes via N-Heterocyclic Carbene/Photoredox Cooperative Catalysis

Organic Letters, Journal Year: 2024, Volume and Issue: 26(20), P. 4351 - 4355

Published: May 10, 2024

We report a novel three-component radical acylfluoroalkylation of 1,3-enynes by synergistic N-heterocyclic carbene (NHC)/photoredox catalysis toward various fluorinated allenic aryl ketones. This protocol features broad substrate scope and excellent functional group tolerability, with examples late-stage modification drug molecules natural products. Notably, seven different fluoroalkyl motifs can be introduced to 1,3-enynes, further demonstrating the robustness generality this method. The generation from each sulfinate reagent was individually supported EPR experiments.

Language: Английский

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