928214-87-3Relevant academic research and scientific papers
TRUNCATED ITRACONAZOLE ANALOGUES AND METHODS OF USE THEREOF
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Paragraph 0097; 0122, (2021/02/19)
Disclosed herein are analogues of itraconazole that are potent hedgehog signaling pathway inhibitors. The compounds are expected to be useful in the treatment of cell proliferation disorders such as cancer, particularly cancers that are dependent upon the hedgehog signaling pathway such as basal cell carcinoma and medulloblastoma.
Truncated Itraconazole Analogues Exhibiting Potent Anti-Hedgehog Activity and Improved Drug-like Properties
Wen, Jiachen,Chennamadhavuni, Divya,Morel, Shana R.,Hadden, M. Kyle
supporting information, p. 1290 - 1295 (2019/09/30)
We conducted a structure-activity relationship study to explore simplified analogues of the itraconazole (ITZ) scaffold for their ability to inhibit the hedgehog (Hh) signaling pathway. These analogues were based on exploring the effects of chemical modifications to the linker and triazolone/side chain region of ITZ. Analogue 11 was identified as the most potent compound in our first generation, with an IC50 value of 81 nM in a murine Hh-dependent basal cell carcinoma. Metabolic identification studies led us to identify truncated piperazine (26) as the major metabolite in human liver microsomes (HLMs) and an improved Hh pathway inhibitor (IC50 = 22 nM). This work verifies that continued truncation of the ITZ scaffold is a practical method to maintain potent anti-Hh activity while also reducing the molecular weight for the ITZ scaffold and achieving improved pharmacokinetic properties.
Synthesis of n′-allyl-2-styrylchromones by a Baker Venkataraman transformation
Barros, Ana I. R. N. A.,Silva, Artur M. S.
, p. 141 - 150 (2007/10/03)
n′-allyl-2-styrylchromones have been prepared by the Baker-Venkataraman method, by two different synthetic routes, both of them involving a Claisen rearrangement. The two synthetic routes were compared in terms of yields and practical execution. All compo
