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Design, synthesis and biological evaluation of anthranilamide derivatives as potent SMO inhibitors
A series of anthranilamide derivatives were designed and synthesized as novel smoothened (SMO) inhibitors based on the SMO inhibitor taladegib (LY2940680), which can also inhibit the SMO-D473H mutant, via a ring-opening strategy. The phthalazine core in LY2940680 was replaced with anthranilamide, which retained the inhibitory activity towards the hedgehog (Hh) signaling pathway as evidenced by a dual luciferase reporter gene assay. Compound 12a displayed the best inhibitory activity against the Hh signaling pathway with IC50 value of 34.09 nM, and exhibited better proliferation inhibitory activity towards the Daoy cell line (IC50 = 0.48 muM) than LY2940680 (IC50 = 0.79 muM).
Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data. Recommanded Product: tert-Butyl 4-(methylamino)piperidine-1-carboxylate, If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 147539-41-1, in my other articles.
Reference£º
Piperidine – Wikipedia,
Piperidine | C5H17222N – PubChem