HG-10-102-01 and Parkinson-Disease

HG-10-102-01 has been researched along with Parkinson-Disease* in 2 studies

Other Studies

2 other study(ies) available for HG-10-102-01 and Parkinson-Disease

Article	Year
Synthesis of [ Bioorganic & medicinal chemistry letters, 2017, 03-15, Volume: 27, Issue:6 Topics: Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; para-Aminobenzoates; Parkinson Disease; Positron-Emission Tomography; Pyrimidines; Radiopharmaceuticals	2017
Discovery of highly potent, selective, and brain-penetrable leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. Journal of medicinal chemistry, 2012, Nov-26, Volume: 55, Issue:22 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. Topics: Animals; Brain; Drug Design; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Macaca fascicularis; Mice; Mice, Transgenic; Models, Molecular; Morpholines; Parkinson Disease; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Pyrimidines; Rats; Small Molecule Libraries; Tissue Distribution	2012

Article

Year

Bioorganic & medicinal chemistry letters, 2017, 03-15, Volume: 27, Issue:6

Topics: Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; para-Aminobenzoates; Parkinson Disease; Positron-Emission Tomography; Pyrimidines; Radiopharmaceuticals

2017

Discovery of highly potent, selective, and brain-penetrable leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors.

Journal of medicinal chemistry, 2012, Nov-26, Volume: 55, Issue:22

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.

Topics: Animals; Brain; Drug Design; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Macaca fascicularis; Mice; Mice, Transgenic; Models, Molecular; Morpholines; Parkinson Disease; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Pyrimidines; Rats; Small Molecule Libraries; Tissue Distribution

2012