scyx-7158 and Neglected-Diseases

scyx-7158 has been researched along with Neglected-Diseases* in 1 studies

Other Studies

1 other study(ies) available for scyx-7158 and Neglected-Diseases

Article	Year
Kinase scaffold repurposing for neglected disease drug discovery: discovery of an efficacious, lapatinib-derived lead compound for trypanosomiasis. Journal of medicinal chemistry, 2013, May-23, Volume: 56, Issue:10 Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei . Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for neglected diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogues of 1, which provided an excellent starting point for optimization of the chemotype. Our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU617, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new chemical tool for studying regulation of the trypanosome cell cycle. Topics: Animals; Cell Cycle; Cell Line, Tumor; Cell Survival; Coloring Agents; Drug Design; Drug Discovery; ErbB Receptors; Humans; Indicators and Reagents; Lapatinib; Morpholines; Neglected Diseases; Phosphotransferases; Quinazolines; Structure-Activity Relationship; Tetrazolium Salts; Thiazoles; Trypanocidal Agents; Trypanosoma brucei brucei; Trypanosomiasis, African	2013

Article

Year

Kinase scaffold repurposing for neglected disease drug discovery: discovery of an efficacious, lapatinib-derived lead compound for trypanosomiasis.

Journal of medicinal chemistry, 2013, May-23, Volume: 56, Issue:10

Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei . Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for neglected diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogues of 1, which provided an excellent starting point for optimization of the chemotype. Our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU617, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new chemical tool for studying regulation of the trypanosome cell cycle.

Topics: Animals; Cell Cycle; Cell Line, Tumor; Cell Survival; Coloring Agents; Drug Design; Drug Discovery; ErbB Receptors; Humans; Indicators and Reagents; Lapatinib; Morpholines; Neglected Diseases; Phosphotransferases; Quinazolines; Structure-Activity Relationship; Tetrazolium Salts; Thiazoles; Trypanocidal Agents; Trypanosoma brucei brucei; Trypanosomiasis, African

2013