766543-59-3Relevant academic research and scientific papers
Design, chemical synthesis, and in vitro biological evaluation of simplified estradiol-adenosine hybrids as inhibitors of 17β-hydroxysteroid dehydrogenase type 1
Berube, Marie,Poirier, Donald
scheme or table, p. 1180 - 1199 (2009/12/01)
A series of estradiol (E2) derivatives were designed to interact with, both the substrate- and the cofactor-binding sites of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1). These analogues of potent E2-adenosine hybrid inhibitor EM-1745, where the adenosine moiety was replaced by a more stable benzene derivative, were synthesized from estrone using alkene cross-metathesis and Sonogashira coupling reactions as key steps. In vitro biological evaluation of these steroid derivatives revealed that a spacer of 13 methylenes, between the 16β-position of E2 and the adenosine mimic bearing a carboxylic acid, group, gave the best inhibition of 17β-HSD1.
Synthesis of simplified hybrid inhibitors of type 1 17β-hydroxysteroid dehydrogenase via cross-metathesis and Sonogashira coupling reactions
Berube, Marie,Poirier, Donald
, p. 3127 - 3130 (2007/10/03)
(Chemical Equation Presented) The inhibitor of type 1 17β- hydroxysteroid dehydrogenase EM-1745 (1) exhibits affinity for both the substrate (estrone or estradiol) and the cofactor (NAD(P)H) binding domains. However, to increase its bioavailability, this compound needs to be simplified. The efficient and convergent synthesis of simplified substrate/cofactor hybrid inhibitors (compounds 2) involving a cross-metathesis and a Sonogashira coupling reaction as key steps is described. Compounds 2a-c were also tested as enzyme inhibitors and compared to EM-1745.
