- Photochemical C-H Silylation and Hydroxymethylation of Pyridines and Related Structures: Synthetic Scope and Mechanisms
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Considering the synthetic relevance of heteroarenes in various areas ranging from organic synthesis to medicinal chemistry, developing practically simple methodologies to access functionalized heteroarenes is of a significant value. Described herein is an efficient approach for C-H silylation and hydroxymethylation of pyridines and related heterocycles by the combination of silanes or methanol with readily available N-methoxypyridinium ions with a low catalyst loading (2 mol %) under blue light irradiation. The synthetic importance of the developed reactions is demonstrated by the synthesis of biologically relevant compounds. Electron paramagnetic resonance spectroscopy, quantum yield measurements, and density-functional theory calculations allowed us to understand reaction mechanisms of both photocatalytic reactions.
- Rammal, Fatima,Gao, Di,Boujnah, Sondes,Hussein, Aqeel A.,Lalevée, Jacques,Gaumont, Annie-Claude,Morlet-Savary, Fabrice,Lakhdar, Sami
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p. 13710 - 13717
(2020/11/30)
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- Inhibition of 1-deoxy-d-xylulose-5-phosphate reductoisomerase by lipophilic phosphonates: SAR, QSAR, and crystallographic studies
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1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) is a novel target for developing new antibacterial (including antituberculosis) and antimalaria drugs. Forty-one lipophilic phosphonates, representing a new class of DXR inhibitors, were synthesized, among which 5-phenylpyridin-2-ylmethylphosphonic acid possesses the most activity against E. coli DXR (EcDXR) with a K i of 420 nM. Structure-activity relationships (SAR) are discussed, which can be rationalized using our EcDXR:inhibitor structures, and a predictive quantitative SAR (QSAR) model is also developed. Since inhibition studies of DXR from Mycobacterium tuberculosis (MtDXR) have not been performed well, 48 EcDXR inhibitors with a broad chemical diversity were found, however, to generally exhibit considerably reduced activity against MtDXR. The crystal structure of a MtDXR:inhibitor complex reveals the flexible loop containing the residues 198-208 has no strong interactions with the 3,4-dichlorophenyl group of the inhibitor, representing a structural basis for the reduced activity. Overall, these results provide implications in the future design and development of potent DXR inhibitors.
- Deng, Lisheng,Diao, Jiasheng,Chen, Pinhong,Pujari, Venugopal,Yao, Yuan,Cheng, Gang,Crick, Dean C.,Prasad, B. V. Venkataram,Song, Yongcheng
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p. 4721 - 4734
(2011/09/19)
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- SPIROPYRROLIDINE BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE
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The present invention is directed to spiropyrrolidine compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease.
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Preparation III.3
(2010/09/17)
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- 2-pyridine Derivatives: New Antiinflammatory Agents
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2-pyridine derivatives (1a-e) inhibited the dermal reverse passive Arthus reaction (RPAR) in the rat.In the same model, indomethacin was inactive, and hydrocortisone was active.Compounds 1a-d also significantly reduced exudate volume and white blood cell accumulation in the pleural RPAR.This pattern of activity was similar to that of hydrocortisone and different from that of indomethacin.
- Haviv, Fortuna,DeNet, Robert W.,Michaels, Raymond J.,Ratajczyk, James D.,Carter, George W.,Young, Patrick R.
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p. 218 - 222
(2007/10/02)
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