scholarly journals Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe

2016 ◽  
Vol 12 ◽  
pp. 1608-1615 ◽  
Author(s):  
Motoyuki Isoda ◽  
Kazuyuki Sato ◽  
Yurika Kunugi ◽  
Satsuki Tokonishi ◽  
Atsushi Tarui ◽  
...  
Keyword(s):  
Cholesterol Absorption ◽  
Unsaturated Ester ◽  
Type Reaction ◽  
Hydride Complex ◽  
Rh Catalyst ◽  
Cholesterol Absorption Inhibitor ◽  
Effective Synthesis

An effective synthesis for syn-β-lactams was achieved using a Rh-catalyzed reductive Mannich-type reaction. A rhodium–hydride complex (Rh–H) derived from diethylzinc (Et2Zn) and a Rh catalyst was used for the 1,4-reduction of an α,β-unsaturated ester to give a Reformatsky-type reagent, which in turn, reacted with an imine to give the syn-β-lactam. Additionally, the reaction was applied to the synthesis of (±)-ezetimibe, a potent β-lactamic cholesterol absorption inhibitor.

scholarly journals Comparison of the activity and disposition of the novel cholesterol absorption inhibitor, SCH58235, and its glucuronide, SCH60663

2000 ◽  
Vol 129 (8) ◽  
pp. 1748-1754 ◽  
Author(s):  
Margaret Van Heek ◽  
Constance Farley ◽  
Douglas S Compton ◽  
Lizbeth Hoos ◽  
Kevin B Alton ◽  
...  
Keyword(s):  
Cholesterol Absorption ◽  
The Novel ◽  
Cholesterol Absorption Inhibitor

scholarly journals Ezetimibe Prevents Ischemia/Reperfusion-Induced Oxidative Stress and Up-Regulates Nrf2/ARE and UPR Signaling Pathways

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 349 ◽  
Author(s):  
Denise Peserico ◽  
Chiara Stranieri ◽  
Ulisse Garbin ◽  
Chiara Mozzini C ◽  
Elisa Danese ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Cultured Cells ◽  
Ischemia Reperfusion ◽  
Cholesterol Absorption ◽  
Antioxidant Response ◽  
Related Factor ◽  
Cellular Models ◽  
Compound C ◽  
Cholesterol Absorption Inhibitor

Background: While reperfusion is crucial for survival after an episode of ischemia, it also causes oxidative stress. Nuclear factor-E2-related factor 2 (Nrf2) and unfolded protein response (UPR) are protective against oxidative stress and endoplasmic reticulum (ER) stress. Ezetimibe, a cholesterol absorption inhibitor, has been shown to activate the AMP-activated protein kinase (AMPK)/Nrf2 pathway. In this study we evaluated whether Ezetimibe affects oxidative stress and Nrf2 and UPR gene expression in cellular models of ischemia-reperfusion (IR). Methods: Cultured cells were subjected to simulated IR with or without Ezetimibe. Results: IR significantly increased reactive oxygen species (ROS) production and the percentage of apoptotic cells without the up-regulation of Nrf2, of the related antioxidant response element (ARE) gene expression or of the pro-survival UPR activating transcription factor 6 (ATF6) gene, whereas it significantly increased the pro-apoptotic CCAAT-enhancer-binding protein homologous protein (CHOP). Ezetimibe significantly decreased the cellular ROS formation and apoptosis induced by IR. These effects were paralleled by the up-regulation of Nrf2/ARE and ATF6 gene expression and by a down-regulation of CHOP. We also found that Nrf2 activation was dependent on AMPK, since Compound C, a pan inhibitor of p-AMPK, blunted the activation of Nrf2. Conclusions: Ezetimibe counteracts IR-induced oxidative stress and induces Nrf2 and UPR pathway activation.

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