De novo design of small molecule inhibitors targeting the LEDGF/p75-HIV integrase interaction was written by Cavalluzzo, Claudia;Voet, Arnout;Christ, Frauke;Singh, Brajendra Kumar;Sharma, Ajendra;Debyser, Zeger;De Maeyer, Marc;Van der Eycken, Erik. And the article was included in RSC Advances in 2012.Application In Synthesis of 3-Amino-2,6-dimethoxypyridine This article mentions the following:
The integration of the viral DNA into the host genome is one of the essential steps in the HIV replication cycle. This multistep process mediated by the viral enzyme integrase (IN) allows identification and development of inhibitors targeting different integrase activities. Lens epithelium-derived growth factor (LEDGF/p75) has recently been identified as a crucial cellular co-factor of integration that acts by tethering IN to the cellular chromatin. Small mols. inhibiting the LEDGF/p75-IN interaction may become new and highly active antiretroviral therapeutic agents. In this paper we report the rational design, synthesis and evaluation of inhibitors that target the LEDGF/p75 protein and compete with IN binding. These mols. are designed to mimic the integrase alpha-3 helix, which interacts with LEDGF/p75, using pharmacophore guided scaffold replacement. The inhibitor 3-(1H-indol-3-ylthio)-N-(2-isopropoxy-6-methoxypyridin-3-yl)benzamide (CAB1) and its derivatives (CAB2-13) inhibit the LEDGF/p75-IN protein-protein interaction with moderate potency. These CAB inhibitors are the first reported example of small mols. targeting the LEDGF/p75 partner of the protein-protein interaction, in contrast to the previously reported compounds which target the integrase partner. In the experiment, the researchers used many compounds, for example, 3-Amino-2,6-dimethoxypyridine (cas: 28020-37-3Application In Synthesis of 3-Amino-2,6-dimethoxypyridine).
3-Amino-2,6-dimethoxypyridine (cas: 28020-37-3) belongs to pyridine derivatives. Pyridines are an important class of heterocycles and occur in polysubstituted forms in many naturally occurring biologically active compounds, drug molecules and chiral ligands. Reduced pyridines, namely tetrahydropyridines, dihydropyridines and piperidines, are found in numerous natural and synthetic compounds. The synthesis and reactivity of these compounds have often been driven by the fact many of these compounds have interesting and unique pharmacological properties. Application In Synthesis of 3-Amino-2,6-dimethoxypyridine