52177-07-8Relevant academic research and scientific papers
Synthesis and biological evaluation of indolyl-pyridinyl-propenones having either methuosis or microtubule disruption activity
Trabbic, Christopher J.,Overmeyer, Jean H.,Alexander, Evan M.,Crissman, Emily J.,Kvale, Heather M.,Smith, Marcie A.,Erhardt, Paul W.,Maltese, William A.
, p. 2489 - 2512 (2015/03/30)
Methuosis is a form of nonapoptotic cell death characterized by an accumulation of macropinosome-derived vacuoles with eventual loss of membrane integrity. Small molecules inducing methuosis could offer significant advantages compared to more traditional anticancer drug therapies that typically rely on apoptosis. Herein we further define the effects of chemical substitutions at the 2-and 5-indolyl positions on our lead compound 3-(5-methoxy-2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propene-1-one (MOMIPP). We have identified a number of compounds that induce methuosis at similar potencies, including an interesting analogue having a hydroxypropyl substituent at the 2-position. In addition, we have discovered that certain substitutions on the 2-indolyl position redirect the mode of cytotoxicity from methuosis to microtubule disruption. This switch in activity is associated with an increase in potency as large as 2 orders of magnitude. These compounds appear to represent a new class of potent microtubule-active anticancer agents.
NOVEL INDAZOLE DERIVATIVE
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Page/Page column 42-43, (2008/06/13)
An object of the present invention is to create a novel indazole derivative useful as a drug and to find a novel pharmacological action of the derivative. The compound of the present invention is represented by the formula [I] and has an excellent Rho kinase inhibiting action. In the formula, a ring X is a benzene ring or a pyridine ring; R1 and R2 are H or alkyl; R3 and R4 are halogen, H, OH, alkoxy, alkenyloxy, alkynyloxy, cycloalkyloxy, cycloalkenyloxy, aryloxy, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, carboxy, hydrocarbonyl, alkylcarbonyl, etc.; and R5 is halogen atom, H, OH, alkoxy, aryloxy, alkyl or aryl. Each group can be substituted.
