HSD1787, a Tetrahydro-3H-Pyrazolo[4,3-f]Quinoline Compound Synthesized via Povarov Reaction, Potently Inhibits Proliferation of Cancer Cell Lines at Nanomolar Concentrations

摘要

Multicomponent reaction (MCR) is often used to rapidly assemble complex compounds for drug screening. Povarov MCR has been used to prepare a new library containing tetrahydro-3H -pyrazolo[4,3-f ]quinoline core and the library tested against MDA-MB-231 (a triple-negative breast cancer, TNBC, cell line). A few of the tetrahydro-3H -pyrazolo[4,3-f ]quinoline-containing compounds, bearing 3-aminoindazolyl group, potently inhibited MDA-MB-231. The most active compound, HSD1787, was evaluated against NCI60 cell lines and this compound inhibited melanoma, renal, breast, ovarian, and leukemia cancer cell lines with GI_(50) values as low as 0.1 μM. The tetrahydro-3H -pyrazolo[4,3-f ]quinoline core is therefore a new scaffold that could be developed into potent anticancer therapeutics against difficult-to-treat cancers.