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Your search keyword '"Stasi, Luigi"' showing total 5 results
Start Over Author "Stasi, Luigi" Publication Year Range Last 10 years Language english
5 results on '"Stasi, Luigi"'

4. Discovery of 5-substituent-N-arylbenzamide derivatives as potent, selective and orally bioavailable LRRK2 inhibitors

Author

Ding, Xiao, Dai, Xuedong, Long, Kai, Peng, Cheng, Andreotti, Daniele, Bamborough, Paul, Eatherton, Andrew J., Edge, Colin, Jandu, Karamjit S., Nichols, Paula L., Philps, Oliver J., Stasi, Luigi Piero, Wan, Zehong, Xiang, Jia-Ning, Dong, Kelly, Dossang, Pamela, Ho, Ming-Hsun, Li, Yi, Mensah, Lucy, Guan, Xiaoming, Reith, Alastair D., and Ren, Feng

Published
2017
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5. 5-Substituted-N-pyridazinylbenzamides as potent and selective LRRK2 inhibitors: Improved brain unbound fraction enables efficacy.

Author

Ding, Xiao, Stasi, Luigi Piero, Dai, Xuedong, Long, Kai, Peng, Cheng, Zhao, Baowei, Wang, Hailong, Sun, Changhui, Hu, Huan, Wan, Zehong, Jandu, Karamjit S., Philps, Oliver J., Chen, Yan, Wang, Lizhen, Liu, Qian, Edge, Colin, Li, Yi, Dong, Kelly, Guan, Xiaoming, and Tattersall, F. David

Subjects
*BENZAMIDE, *ENZYME inhibitors, *BRAIN physiology, *PHOSPHORYLATION, *PHARMACOKINETICS
Abstract

Graphical abstract Abstract We describe the discovery and optimization of 5-substituted-N-pyridazinylbenzamide derivatives as potent and selective LRRK2 inhibitors. Extensive SAR studies led to the identification of compounds 18 and 23 , which demonstrated good in vitro pharmacokinetic profile and excellent selectivity over 140 other kinases. Both compounds demonstrated high unbound fractions in both blood and brain. Compound 18 proved to be brain penetrant, and the high unbound fraction of compound 18 in brain enabled its in vivo efficacy in CNS, wherein a significant inhibition of LRRK2 Ser935 phosphorylation was observed in rat brain following intravenous infusion at 5 mg/kg/h. [ABSTRACT FROM AUTHOR]

Published
2019
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