Three efficient methods to synthesize mono- and di-fluorinated benzimidazoles are reported. These methods provide 5-amino-6-fluoro-benzimidazoles （5）, 5,7-difluoro-benzimidazoles （10）, and 6-fluoro-benzimidazoles ...Three efficient methods to synthesize mono- and di-fluorinated benzimidazoles are reported. These methods provide 5-amino-6-fluoro-benzimidazoles （5）, 5,7-difluoro-benzimidazoles （10）, and 6-fluoro-benzimidazoles （13） starting from commercially available 1,5-difluoro-2,4-dinitrobenzene （DFDNB）, 2,3,4,5-tetrafluoro-6-nitrobenzoic acid （TFNBA）, and 2,4-difluoro-l-nitrobenzene （DFNB）, respectively.展开更多
This overview summarizes recent advanced literature surveys on the synthesis of fluorine substituted 1,2,4-triazine containing various functional groups and/or the related hetero-polycyclic nitrogen systems have been ...This overview summarizes recent advanced literature surveys on the synthesis of fluorine substituted 1,2,4-triazine containing various functional groups and/or the related hetero-polycyclic nitrogen systems have been reported. In addition, physical, chemical, and medicinal properties have been evaluated. The presence of fluorinated atoms often improves these properties with an increasing electronegativity. It, also, enhances the stability of formed carbanion and it improves the hydrophobic effects which have good biological activities.展开更多
Thirteen new fluorine-containing drugs,which have been granted approval by the US Food and Drug Administration(FDA)in 2020,are profiled in this review.Therapeutic areas of these new fluorinated pharmaceuticals include...Thirteen new fluorine-containing drugs,which have been granted approval by the US Food and Drug Administration(FDA)in 2020,are profiled in this review.Therapeutic areas of these new fluorinated pharmaceuticals include medicines and diagnostic agents for Cushing's disease,neurofibromatosis,migraine,Alzheimer's disease,myelodysplastic syndromes,hereditary angioedema attacks,and various cancers.Molecules of these approved drugs feature aromatic fluorine(Ar-F)(11 compounds),aromatic Ar-CF_(3)(1),aliphatic CHF(1)and CF_(2)(1)groups.For each compound,we provide a spectrum of biological activity,medicinal chemistry discovery,and synthetic approaches.展开更多
Some 1,2,5-trisubstituted benzimidazole fluorinated derivatives were designed and screened by moleculardocking. Five compounds which obtained high scores were selected to synthesize. All the target products were cha-r...Some 1,2,5-trisubstituted benzimidazole fluorinated derivatives were designed and screened by moleculardocking. Five compounds which obtained high scores were selected to synthesize. All the target products were cha-racterized by 1H NMR, 13C NMR and high resolution mass spectra（HRMS） and preliminarily screened for inhibitoryactivity against thrombin, among which three compounds（5a, 5c and 5e） were evaluated in vitro. The results showedthat compounds 5a, 5c and 5e exhibited better anticoagulant activity than argatroban. Docking simulations demon-strated that these compoands may act as candidates for further studies on thrombin inhibitors.展开更多
文摘Three efficient methods to synthesize mono- and di-fluorinated benzimidazoles are reported. These methods provide 5-amino-6-fluoro-benzimidazoles （5）, 5,7-difluoro-benzimidazoles （10）, and 6-fluoro-benzimidazoles （13） starting from commercially available 1,5-difluoro-2,4-dinitrobenzene （DFDNB）, 2,3,4,5-tetrafluoro-6-nitrobenzoic acid （TFNBA）, and 2,4-difluoro-l-nitrobenzene （DFNB）, respectively.
文摘This overview summarizes recent advanced literature surveys on the synthesis of fluorine substituted 1,2,4-triazine containing various functional groups and/or the related hetero-polycyclic nitrogen systems have been reported. In addition, physical, chemical, and medicinal properties have been evaluated. The presence of fluorinated atoms often improves these properties with an increasing electronegativity. It, also, enhances the stability of formed carbanion and it improves the hydrophobic effects which have good biological activities.
基金the financial support from the National Natural Science Foundation of China(No.21761132021)IKERBASQUE,Basque Foundation for Science.
文摘Thirteen new fluorine-containing drugs,which have been granted approval by the US Food and Drug Administration(FDA)in 2020,are profiled in this review.Therapeutic areas of these new fluorinated pharmaceuticals include medicines and diagnostic agents for Cushing's disease,neurofibromatosis,migraine,Alzheimer's disease,myelodysplastic syndromes,hereditary angioedema attacks,and various cancers.Molecules of these approved drugs feature aromatic fluorine(Ar-F)(11 compounds),aromatic Ar-CF_(3)(1),aliphatic CHF(1)and CF_(2)(1)groups.For each compound,we provide a spectrum of biological activity,medicinal chemistry discovery,and synthetic approaches.
文摘Some 1,2,5-trisubstituted benzimidazole fluorinated derivatives were designed and screened by moleculardocking. Five compounds which obtained high scores were selected to synthesize. All the target products were cha-racterized by 1H NMR, 13C NMR and high resolution mass spectra（HRMS） and preliminarily screened for inhibitoryactivity against thrombin, among which three compounds（5a, 5c and 5e） were evaluated in vitro. The results showedthat compounds 5a, 5c and 5e exhibited better anticoagulant activity than argatroban. Docking simulations demon-strated that these compoands may act as candidates for further studies on thrombin inhibitors.
