Synthesis of Simplified Hybrid Inhibitors of Type 1 17β-Hydroxysteroid Dehydrogenase via Cross-Metathesis and Sonogashira Coupling Reactions

2004 ◽  
Vol 6 (18) ◽  
pp. 3127-3130 ◽  
Author(s):  
Marie Bérubé ◽  
Donald Poirier
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Coupling Reactions ◽  
Sonogashira Coupling ◽  
Cross Metathesis

Design, chemical synthesis, and in vitro biological evaluation of simplified estradiol–adenosine hybrids as inhibitors of 17β-hydroxysteroid dehydrogenase type 1

2009 ◽  
Vol 87 (8) ◽  
pp. 1180-1199 ◽  
Author(s):  
Marie Bérubé ◽  
Donald Poirier
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Acid Group ◽  
Biological Evaluation ◽  
Benzene Derivative ◽  
Coupling Reactions ◽  
Cofactor Binding ◽  
Cross Metathesis ◽  
Key Steps

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.

scholarly journals Synthesis of novel 13α-estrone derivatives by Sonogashira coupling as potential 17β-HSD1 inhibitors

2017 ◽  
Vol 13 ◽  
pp. 1303-1309 ◽  
Author(s):  
Ildikó Bacsa ◽  
Rebeka Jójárt ◽  
János Wölfling ◽  
Gyula Schneider ◽  
Bianka Edina Herman ◽  
...  
Keyword(s):  
Methyl Ether ◽  
Hydroxysteroid Dehydrogenase ◽  
Coupling Reactions ◽  
Sonogashira Coupling ◽  
Partial Saturation ◽  
Inhibitory Effects ◽  
Microwave Reactor ◽  
Incubation Method

Novel 13α-estrone derivatives were synthesized by Sonogashira coupling. Transformations of 2- or 4-iodo regioisomers of 13α-estrone and its 3-methyl ether were carried out under different conditions in a microwave reactor. The 2-iodo isomers were reacted with para-substituted phenylacetylenes using Pd(PPh3)4 as catalyst and CuI as a cocatalyst. Coupling reactions of 4-iodo derivatives could be achieved by changing the catalyst to Pd(PPh3)2Cl2. The product phenethynyl derivatives were partially or fully saturated. Compounds bearing a phenolic OH group furnished benzofurans under the conditions used for the partial saturation. The inhibitory effects of the compounds on human placental 17β-hydroxysteroid dehydrogenase type 1 isozyme (17β-HSD1) were investigated by an in vitro radiosubstrate incubation method. Certain 3-hydroxy-2-phenethynyl or -phenethyl derivatives proved to be potent 17β-HSD1 inhibitors, displaying submicromolar IC50 values.

Homo- and heterogeneous Ru-based metathesis catalysts in cross-metathesis of 15-allylestrone—towards 17β-hydroxysteroid dehydrogenase type 1 inhibitors

2008 ◽  
Vol 49 (18) ◽  
pp. 3019-3022 ◽  
Author(s):  
Andreas Kirschning ◽  
Kirsten Harmrolfs ◽  
Klaas Mennecke ◽  
Josef Messinger ◽  
Uwe Schön ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Cross Metathesis ◽  
Metathesis Catalysts

The role of hepatic 11[b]-hydroxysteroid dehydrogenase type 1 in cholesterol homeostasis

2013 ◽  
pp. 1-1
Author(s):  
Kajal Manwani ◽  
Tak Y Man ◽  
Christopher J Kenyon ◽  
Ruth Andrew ◽  
Karen E Chapman ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Cholesterol Homeostasis

Macrophage-specific 11b-hydroxysteroid dehydrogenase type 1 deficiency promotes angiogenesis but impairs resolution of K/BxN serum induced arthritis

2013 ◽  
pp. 1-1
Author(s):  
Zhenguang Zhang ◽  
Agnes Coutinho ◽  
Patrick Hadoke ◽  
Donald Salter ◽  
Jonathan Seckl ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase

Suppression of 11[beta]-hydroxysteroid dehydrogenase type 1 target gene regulation by hypoxia

2016 ◽  
Author(s):  
Bushra Shammout ◽  
Adewonuola Alase ◽  
Miriam Wittmann ◽  
Paul Stewart ◽  
Ana Tiganescu
Keyword(s):  
Gene Regulation ◽  
Target Gene ◽  
Hydroxysteroid Dehydrogenase
Sign in / Sign up

Export Citation Format

Share Document