Conversion of Quinazoline Modulators from Inhibitors to Activators of 尾-Glucocerebrosidase was written by Zheng, Jianbin;Jeon, Sohee;Jiang, Weilan;Burbulla, Lena F.;Ysselstein, Daniel;Oevel, Kristine;Krainc, Dimitri;Silverman, Richard B.. And the article was included in Journal of Medicinal Chemistry in 2019.Computed Properties of C11H12N2 This article mentions the following:
Gaucher’s disease is a lysosomal disease caused by mutations in the 尾-glucocerebrosidase gene (GBA1 and GCase) that have been also linked to increased risk of Parkinson’s disease (PD) and Diffuse Lewy body dementia. Prior studies have suggested that mutant GCase protein undergoes misfolding and degradation, and therefore, stabilization of the mutant protein represents an important therapeutic strategy in synucleinopathies. In this work, we present a structure-activity relationship (SAR) study of quinazoline compounds that serve as inhibitors of GCase. Unexpectedly, we found that N-methylation of these inhibitors transformed them into GCase activators. A systematic SAR study further revealed that replacement of the key oxygen atom in the linker of the quinazoline derivative also contributed to the activity switch. PD patient-derived fibroblasts and dopaminergic midbrain neurons were treated with a selected compound (9q) that partially stabilized GCase and improved its activity. These results highlight a novel strategy for therapeutic development of noninhibitory GCase modulators in PD and related synucleinopathies. In the experiment, the researchers used many compounds, for example, 2,3,4,9-Tetrahydro-1H-pyrido[3,4-b]indole (cas: 16502-01-5Computed Properties of C11H12N2).
2,3,4,9-Tetrahydro-1H-pyrido[3,4-b]indole (cas: 16502-01-5) belongs to indole derivatives. Indole produced by Proteus, Pseudomonas, Escherichia and other species was shown to be a growth promoting factor in Arabidopsis thaliana. They are capable of binding to a variety of receptors with high affinity and thus have applications in a wide range of therapeutic areas.Computed Properties of C11H12N2
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Indole alkaloid derivatives as building blocks of natural products from聽Bacillus thuringiensis聽and聽Bacillus velezensis聽and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles