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

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 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.

Язык: Английский

Direct Decarboxylation of Trifluoroacetates Enabled by Iron Photocatalysis DOI Creative Commons
Sara Fernández‐García, Veronika O. Chantzakou, Francisco Juliá‐Hernández

и другие.

Опубликована: Авг. 16, 2023

Trifluoroacetates are the most abundant and accessible sources of trifluoromethyl groups, which key components in pharmaceuticals agrochemicals. The generation reactive radicals from trifluoroacetates requires their decarboxylation, is hampered by high oxidation potential. This constitutes a major challenge for redox-based methods, because need to pair redox potentials with trifluoroacetate. Here we report strategy based on iron photocatalysis promote direct photodecarboxylation that displays reactivity features escape limitations. Our synthetic design has enabled use trifluoromethylation more easily oxidizable organic substrates, offering new opportunities late-stage derivatization campaigns using chemical feedstocks, Earth-abundant catalysts, visible-light.

Язык: Английский

Процитировано

3
Dearomative tandem annulation to access chiral indoline-fused bicyclo[2.2.2]octanes using modularly designed organocatalysts DOI

Wen‐Lin Zou,

Yanqing Liu, Qing‐Zhu Li

и другие.

Organic Chemistry Frontiers, Год журнала: 2023, Номер 10(5), С. 1237 - 1244

Опубликована: Янв. 1, 2023

An asymmetric dearomative tandem annulation between 3-nitroindoles and 7-oxo-5-heptenals was developed by using modularly designed organocatalysts self-assembled from cinchona-squaramide d -proline.

Язык: Английский

Процитировано

2
Isotopologues of Potassium 2,2,2-Trifluoroethoxide for Applications in Positron Emission Tomography and Beyond DOI Creative Commons
Victor W. Pike, Qunchao Zhao, Sanjay Telu

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Фев. 27, 2024

Abstract The 2.2.2-trifluoroethoxy group increasingly features in drugs and potential tracers for biomedical imaging with positron emission tomography (PET). Herein, we describe a novel rapid metal-free conversion of fluoroform paraformaldehyde into highly reactive potassium 2,2,2-trifluoroethoxide (CF3CH2OK) demonstrate robust applications this synthon one-pot, two-stage 2,2,2-trifluoroethoxylations both aromatic aliphatic precursors. Moreover, show that these transformations translate easily to has been labeled either carbon-11 (t1/2 = 20.4 min) or fluorine-18 (t1/2 109.8 min), so allowing the appendage complex molecules no-carrier-added 11C- 18F- 2,2,2-trifluoroethoxy group. This provides enormous scope provide new candidate PET radioactive metabolically stable moieties. We also exemplify syntheses isotopologues their utility isotopic labeling which can be further benefit drug discovery development.

Язык: Английский

Процитировано

0
Stereoselective skeletal modification of tryptanthrins to install chiral piperidine-2-ones enabled by Brønsted acid catalysis DOI
Rong Zeng, Xiang Zhang, Yuanyuan Lei

и другие.

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(8), С. 2171 - 2177

Опубликована: Янв. 1, 2024

An asymmetric formal [4 + 2] cyclisation between azlactones and aza-dienes derived from simple tryptanthrins has been developed. With this established protocol, yielding a series of novel piperidine-2-one-fused with up to >99 : 1 er under mild conditions.

Язык: Английский

Процитировано

0
F-CPI: Prediction of activity changes induced by fluorine substitution using multimodal deep learning DOI
Qian Zhang, Wenhai Yin, Xinyao Chen

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 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.

Язык: Английский

Процитировано

0