767352-09-0Relevant academic research and scientific papers
Structure-activity relationships of C-17 cyano-substituted estratrienes as anticancer agents
Leese, Mathew P.,Jourdan, Fabrice L.,Gaukroger, Keira,Mahon, Mary F.,Newman, Simon P.,Foster, Paul A.,Stengel, Chloe,Regis-Lydi, Sandra,Ferrandis, Eric,Di Fiore, Anna,De Simone, Giuseppina,Supuran, Claudiu T.,Purohit, Atul,Reed, Michael J.,Potter, Barry V. L.
, p. 1295 - 1308 (2008/12/21)
The synthesis, SAR, and preclinical evaluation of 17-cyanated 2-substituted estra-1,3,5(10)-trienes as anticancer agents are discussed. 2-Methoxy-17β-cyanomethylestra-1,3,5(10)-trien-3-ol (14), but not the related 2-ethyl derivative 7, and the related 3-O-sulfamates 8 and 15 display potent antiproliferative effects (MCF-7 GI50 300, 60 and 70 nM, respectively) against human cancer cells in vitro. Investigation of the SAR reveals that a sterically unhindered hydrogen bond acceptor attached to C-17 is most likely key to the enhanced activity. Compound 8 displayed significant in vitro antiangiogenic activity, and its ability to act as a microtubule disruptor was confirmed. Inhibitory activity of the sulfamate derivatives against steroid sulfatase and carbonic anhydrase II (hCAII) was also observed, and the interaction between 15 and hCAII was investigated by protein crystallography. The potential of these multimechanism anticancer agents was confirmed in vivo, with promising activity observed for both 14 and 15 in an athymic nude mouse MDA-MB-231 human breast cancer xenograft model.
17β-HSD1 AND STS INHIBITORS
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Page/Page column 86, (2010/11/25)
The present invention relates to novel substituted steroid derivatives which represent selectiv inhibitors of the 17β-hydroxysteroid dehydrogenase type I (17β-HSD1) and, in addition, which may represent inhibitors of the steroid sulphatase, as well as to their salts, to pharmaceutical preparations containing these compounds and to processes for the preparation of these compounds. Furthermore, the invention concerns the therapeutic use of said novel substituted steroid derivatives, particularly their use in the treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of 17β-hydroxysteroid dehydrogenase type I and/or steroid sulphatase enzymes and/or requiring the lowering of the endogenous 17β-estradiol concentration.
Novel and potent 17β-hydroxysteroid dehydrogenase type 1 inhibitors
Lawrence, Harshani R.,Vicker, Nigel,Allan, Gillian M.,Smith, Andrew,Mahon, Mary F.,Tutill, Helena J.,Purohit, Atul,Reed, Michael J.,Potter, Barry V. L.
, p. 2759 - 2762 (2007/10/03)
Structure-based drug design using the crystal structure of human 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) led to the discovery of novel, selective, and the most potent inhibitors of 17β-HSD1 reported to date. Compounds 1 and 2 contain a side cha
