1383426-76-3Relevant academic research and scientific papers
Syntheses, biological evaluation and SAR of ingenol mebutate analogues for treatment of actinic keratosis and non-melanoma skin cancer
Liang, Xifu,Grue-Sorensen, Gunnar,Mansson, Kristoffer,Vedso, Per,Soor, Anke,Stahlhut, Martin,Bertelsen, Malene,Engell, Karen Margrethe,Hoegberg, Thomas
, p. 5624 - 5629 (2013)
Ingenol mebutate is the active ingredient in Picato a new drug for the treatment of actinic keratosis. A number of derivatives related to ingenol mebutate were prepared by chemical synthesis from ingenol with the purpose of investigating the SAR and potency in assays relating to pro-inflammatory effects (induction of PMN oxidative burst and keratinocyte cytokine release), the potential of cell death induction, as well as the chemical stability. By modifications of the ingenol scaffold several prerequisites for activity were identified. The chemical stability of the compounds could be linked to an acyl migration mechanism. We were able to find analogues of ingenol mebutate with comparable in vitro properties. Some key features for potent and more stable ingenol derivatives have been identified.
3-ACYL-INGENOLS II
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Page/Page column 59, (2012/07/13)
The invention relates to compounds of general formula I, (I), wherein R is wherein R is aryl substituted by R3; or R is (C3-Ci3)-cycloalkyl, (C3-Ci3)- cycloalkenyl or (C7-Ci3)-cycloalkynyl optionally substituted by R4; and pharmaceutically acceptable salts, hydrates, or solvates thereof, for use -alone or in combination with one or more other pharmaceutically active compounds- in therapy, for preventing, treating or ameliorating diseases or conditions responsive to stimulation of neutrophil oxidative burst, responsive to stimulation of keratinocyte IL-8 release or responsive to induction of necrosis.
