94085-74-2Relevant academic research and scientific papers
Tetrahydroisoquinolinone-based steroidomimetic and chimeric microtubule disruptors
Leese, Mathew P.,Jourdan, Fabrice L.,Major, Meriel R.,Dohle, Wolfgang,Hamel, Ernest,Ferrandis, Eric,Fiore, Ann,Kasprzyk, Philip G.,Potter, Barry V. L.
, p. 85 - 108 (2014/01/17)
A structure-activity relationship (SAR) translation strategy was used for the discovery of tetrahydroisoquinoline (THIQ)-based steroidomimetic and chimeric microtubule disruptors based upon a steroidal starting point. A steroid A,B-ring-mimicking THIQ core was connected to methoxyaryl D-ring ring mimics through methylene, carbonyl and sulfonyl linkers to afford a number of steroidomimetic hits (e.g., 7-methoxy-2-(3- methoxybenzyl)-6-sulfamoyloxy-1,2,3, 4-tetrahydroisoquinoline (20 c) GI50=2.1 μM). Optimisation and control experiments demonstrate the complementary SAR of this series and the steroid derivatives that inspired its design. Linkage of the THIQ-based A,B-mimic with the trimethoxyaryl motif prevalent in colchicine site binding microtubule disruptors delivered a series of chimeric molecules whose activity (GI50=40 nM) surpasses that of the parent steroid derivatives. Validation of this strategy was obtained from the excellent oral activity of 7-methoxy-6-sulfamoyloxy-2-(3,4,5-trimethoxybenzyl)-1,2,3,4- tetrahydroisoquinoline (20 z) relative to a benchmark steroidal bis- sulfamate Copyright
1-(1,3-dioxolan-2-ylmethyl)azoles, their salts and their use
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, (2008/06/13)
New 1-(1,3-dioxolan-2-ylmethyl)azoles, their stereoisomers and their salts are described, as are processes for their preparation. The new compounds are chemotherapeutic agents. They are active against skin fungi, mold fungi and yeasts and against bacteria.
