F-CPI: Prediction of activity changes induced by fluorine substitution using multimodal deep learning DOI
Qian Zhang, Wenhai Yin, Xinyao Chen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 17, 2024

Abstract There are a large number of fluorine (F)-containing compounds in approved drugs, and F substitution is common method drug discovery development. However, difficult to form traditional hydrogen bonds typical halogen bonds. As result, accurate prediction the activity after still impossible using design methods, whereas artificial intelligence driven might offer solution. Although more machine learning deep models being applied, there currently no model specifically designed study effect on bioactivities. In this study, we developed specialized model, F-CPI, predict introducing activity, tested its performance carefully constructed dataset. Comparison with popular CPI task demonstrated superiority necessity achieving an accuracy approximately 89% precision 67%. end, utilized F-CPI for structural optimization hit against SARS-CoV-2 3CL pro . Impressively, one case, introduction only atom resulted than 100-fold increase (IC 50 : 22.99 nM vs. 28190 nM). Therefore, believe that helpful effective tool context design.

Language: Английский

Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials DOI Creative Commons
Xin Xie, Tingting Yu,

Xiang Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 6, 2023

Abstract Undruggable proteins are a class of that often characterized by large, complex structures or functions difficult to interfere with using conventional drug design strategies. Targeting such undruggable targets has been considered also great opportunity for treatment human diseases and attracted substantial efforts in the field medicine. Therefore, this review, we focus on recent development discovery targeting “undruggable” their application clinic. To make review well organized, discuss strategies proteins, including covalent regulation, allosteric inhibition, protein–protein/DNA interaction targeted nucleic acid-based approach, immunotherapy others.

Language: Английский

Citations

158
Scalable decarboxylative trifluoromethylation by ion-shielding heterogeneous photoelectrocatalysis DOI
Yixin Chen, Yuchen He, Yong Gao

et al.

Science, Journal Year: 2024, Volume and Issue: 384(6696), P. 670 - 676

Published: May 9, 2024

Electrochemistry offers a sustainable synthesis route to value-added fine chemicals but is often constrained by competing electron transfer between the electrode and redox-sensitive functionalities distinct from target site. Here, we describe an ion-shielding heterogeneous photoelectrocatalysis strategy impose mass-transfer limitations that invert thermodynamically determined order of transfer. This showcased enable decarboxylative trifluoromethylation sensitive (hetero)arenes using trifluoroacetate, inexpensive yet relatively inert trifluoromethyl group (CF

Language: Английский

Citations

25
Review and Theoretical Analysis of Fluorinated Radicals in Direct CAr−H Functionalization of (Hetero)arenes DOI Creative Commons
Anthony J. Fernandes, Rahul Giri, K. N. Houk

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(16)

Published: Jan. 29, 2024

Abstract We highlight key contributions in the field of direct radical C Ar − H (hetero)aromatic functionalization involving fluorinated radicals. A compilation Functional Group Transfer Reagents and their diverse activation mechanisms leading to release radicals are discussed. The substrate scope for each is analyzed classified into three categories according electronic properties substrates. Density functional theory computational analysis provides insights chemical reactivity several through electrophilicity nucleophilicity parameters. Theoretical reduction potentials also highlights remarkable correlation between oxidizing ability. It established that highly (e.g. ⋅OCF 3 ) capable engaging single‐electron transfer (SET) processes rather than addition, which good agreement with experimental literature data. scale, based on barrier addition these benzene elaborated using high accuracy DLPNO‐(U)CCSD(T) method.

Language: Английский

Citations

20
Bi-Catalyzed Trifluoromethylation of C(sp2)–H Bonds under Light DOI Creative Commons
Takuya Tsuruta, Davide Spinnato, Hye Won Moon

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(47), P. 25538 - 25544

Published: Nov. 14, 2023

We disclose a Bi-catalyzed C–H trifluoromethylation of (hetero)arenes using CF3SO2Cl under light irradiation. The catalytic method permits the direct functionalization various heterocycles bearing distinct functional groups. structural and computational studies suggest that process occurs through an open-shell redox manifold at bismuth, comprising three unusual elementary steps for main group element. cycle starts with rapid oxidative addition to low-valent Bi(I) catalyst, followed by light-induced homolysis Bi(III)–O bond generate trifluoromethyl radical upon extrusion SO2, is closed hydrogen-atom transfer Bi(II) intermediate.

Language: Английский

Citations

35
Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing DOI Creative Commons

Tongyu Huo,

Xin-Yi Zhao, Zengrui Cheng

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(3), P. 1030 - 1076

Published: Nov. 18, 2023

Synthetic chemistry plays an indispensable role in drug discovery, contributing to hit compounds identification, lead optimization, candidate drugs preparation, and so on. As Nobel Prize laureate James Black emphasized, "the most fruitful basis for the discovery of a new is start with old drug"

Language: Английский

Citations

23
Energy-Transfer-Enabled Radical Acylation Using Free Alkyl Boronic Acids through Photo and NHC Dual Catalysis DOI

Wan-Cong Liu,

Xiang Zhang, Lin Chen

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(5), P. 3181 - 3190

Published: Feb. 14, 2024

Cross-coupling reactions have been well received as one of the most popular protocols for ketone synthesis. As an important coupling partner, bench-stable and commercially available alkyl boronic acids are widely used in transition metal catalysis, but they rarely utilized radical precursors acylative reactions. Herein, we reported energy-transfer-enabled acylation using free via NHC/photo dual catalysis. This protocol could efficiently promote Suzuki-type cross-coupling between acyl imidazoles multicomponent alkylacylations alkenes, thus producing various ketones with structural diversity. Additionally, products can readily transform into a large number structurally interesting fine chemicals. Preliminary mechanistic studies shed light on unique reaction mechanism.

Language: Английский

Citations

10
Cooperative photoactivation/Lewis base catalyzed [4 + 2] annulations of α-diazoketones andortho-amino MBH carbonates to access dihydroquinolinone frameworks DOI
Jin Zhou, Chen Chen, Qiwen Pang

et al.

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(4), P. 1034 - 1041

Published: Jan. 1, 2023

A series of dihydroquinolinones have been synthesized via synergistic catalysis combining photolysis and Lewis base utilizing in situ generated ketenes ortho -amino MBH carbonates.

Language: Английский

Citations

14
Electron Donor‐Acceptor Complex Driven Photocatalyst‐Free Trifluoromethylation of Heterocycles DOI
Yufei Li,

Jie Hou,

Pei Zhang

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(31)

Published: April 1, 2024

Heterocyclic trifluoromethylation is efficiently initiated through a photochemical reaction utilizing an electron donor-acceptor (EDA) complex, proceeding smoothly without the use of photocatalysts, transition-metal catalysts, or additional oxidants. This method has been optimized extensive experimentation, demonstrating its versatility and efficacy across various substrates, including quinoxalinones, coumarins, indolones. Notably, this approach enables practical synthesis trifluoromethylated quinoxalinones on gram scale. Mechanistic investigations that incorporate radical trapping ultraviolet/visible spectroscopy, confirmed formation EDA complex elucidated pathways. study highlights crucial role photoactivation in trifluoromethylation, significantly expanding application scope complexes chemical synthesis.

Language: Английский

Citations

4
g-C3N4-Based Heterogeneous Photocatalyzed Synthesis and Evaluation of Antitumor Activities of Fluoroalkylated 4H-Pyrido[1,2-a]pyrimidin-4-ones DOI
Ningbo Li, Yan Liu,

Chu-Qian Hu

et al.

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

The first example of heterogeneous photoredox-catalyzed fluoroalkylation 4H-pyrido[1,2-a]pyrimidin-4-ones has been developed. With low-cost commercial g-C3N4 as the recyclable photocatalyst and cheap sodium fluoroalkyl sulfonates source, a variety fluoroalkylated pyridopyrimidinones were constructed in moderate to high yields. present reaction can be easily scaled up with good efficiency, catalytic system reused 5 times slight loss activities. Furthermore, biological activity synthesized compounds was preliminarily investigated.

Language: Английский

Citations

0
BINAP‐Accelerated Photoinduced Trifluoromethylation of (Hetero)Aryl Iodides DOI Open Access

Xueyan Yang,

Yan Kang, Hai‐Shu Lin

et al.

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

Published: March 6, 2025

Abstract Trifluoromethyl groups hold significance in the bioactivity and physical properties of organic molecules. Contemporary approaches to trifluoromethylated aromatics typically involve coupling CuCF 3 reagents with aryl halides, which is limited by difficulty oxidative addition copper organohalides. Herein, a photoinduced ligand‐catalyzed trifluoromethylation/pentafluoroethylation (hetero)aryl iodides presented. The conversion C─I bond into C─CF enabled photochemistry copper, produces radicals situ generated from Ruppert–Prakash reagent under visible light. This radical approach circumvents challenge catalytic amount rac ‐BINAP substantially accelerates whole process, allowing reaction complete within 1 h very mild conditions without using any additional photo‐redox catalysts. readily availability starting material, high efficiency, broad utility make this transformation attractive for practitioners synthetic medicinal chemistry.

Language: Английский

Citations

0