1401423-29-7Relevant academic research and scientific papers
INDOLE CARBOXAMIDE DERIVATIVES AS P2X7 RECEPTOR ANTAGONISTS
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Page/Page column 95, (2014/07/08)
The invention relates to indole carboxamide derivatives of formula (I), wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and n are as defined in the description, their preparation and their use as pharmaceutically active compounds.
AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS
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Page/Page column 50, (2013/06/27)
Compounds of the formula (I): or pharmaceutically acceptable salts thereof, wherein A, X, R1, R2, R3 and R4 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for t
2-PHENYLAMINOPYRIMIDINE DERIVATIVES AS KINASE LRRK2 MODULATORS FOR THE TREATMENT OF PARKINSON'S DISEASE
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Page/Page column 62; 63, (2013/06/27)
Specific Compounds of formula (I): or pharmaceutically acceptable salts thereof, wherein m, X, R, R2, R3, R, R6 and R7 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.
Discovery of highly potent, selective, and brain-penetrable leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors
Estrada, Anthony A.,Liu, Xingrong,Baker-Glenn, Charles,Beresford, Alan,Burdick, Daniel J.,Chambers, Mark,Chan, Bryan K.,Chen, Huifen,Ding, Xiao,Dipasquale, Antonio G.,Dominguez, Sara L.,Dotson, Jennafer,Drummond, Jason,Flagella, Michael,Flynn, Sean,Fuji, Reina,Gill, Andrew,Gunzner-Toste, Janet,Harris, Seth F.,Heffron, Timothy P.,Kleinheinz, Tracy,Lee, Donna W.,Le Pichon, Claire E.,Lyssikatos, Joseph P.,Medhurst, Andrew D.,Moffat, John G.,Mukund, Susmith,Nash, Kevin,Scearce-Levie, Kimberly,Sheng, Zejuan,Shore, Daniel G.,Tran, Thuy,Trivedi, Naimisha,Wang, Shumei,Zhang, Shuo,Zhang, Xiaolin,Zhao, Guiling,Zhu, Haitao,Sweeney, Zachary K.
, p. 9416 - 9433 (2013/01/16)
There is a high demand for potent, selective, and brain-penetrant small molecule inhibitors of leucine-rich repeat kinase 2 (LRRK2) to test whether inhibition of LRRK2 kinase activity is a potentially viable treatment option for Parkinson's disease patients. Herein we disclose the use of property and structure-based drug design for the optimization of highly ligand efficient aminopyrimidine lead compounds. High throughput in vivo rodent cassette pharmacokinetic studies enabled rapid validation of in vitro-in vivo correlations. Guided by this data, optimal design parameters were established. Effective incorporation of these guidelines into our molecular design process resulted in the discovery of small molecule inhibitors such as GNE-7915 (18) and 19, which possess an ideal balance of LRRK2 cellular potency, broad kinase selectivity, metabolic stability, and brain penetration across multiple species. Advancement of GNE-7915 into rodent and higher species toxicity studies enabled risk assessment for early development.
