Pharmacophore-based design, synthesis, and biological evaluation of novel 3-((3,4-dichlorophenyl)(4-substituted benzyl)amino) propanamides as cholesteryl ester transfer protein (CETP) inhibitors

2014 ◽  
Vol 25 (2) ◽  
pp. 299-304 ◽  
Author(s):  
Dong-Mei Zhao ◽  
Wen-Yan Li ◽  
Yu-Fang Shi ◽  
Xu-Qiong Xiong ◽  
Shuai Song ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Transfer Protein ◽  
Cetp Inhibitors ◽  
Synthesis And Biological Evaluation

Cholesteryl Ester Transfer Protein Inhibitors

2016 ◽  
Vol 22 (2) ◽  
pp. 99-104 ◽  
Author(s):  
Julian Hardy McLain ◽  
Andrew Jacob Alsterda ◽  
Rohit R. Arora
Keyword(s):  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Plasma Cholesterol ◽  
Genetic Research ◽  
Plasma Lipoproteins ◽  
Pharmacologic Therapy ◽  
Atherosclerotic Cardiovascular Disease ◽  
Current Standard ◽  
Transfer Protein ◽  
Cetp Inhibitors

The cholesteryl ester transfer protein (CETP) is a plasma protein that plays an important role in the transfer of lipids between plasma lipoproteins. The CETP inhibitors have been widely studied as a pharmacologic therapy to target plasma cholesterol in order to reduce the risk of atherosclerotic cardiovascular disease . Using CETP inhibitors as cholesterol modifiers was based on the genetic research that found correlations between CETP activity and cholesterol levels. Although CETP inhibitors are successful at altering targeted cholesterol markers, recent phase 3 outcome trials have shown limited benefit on cardiovascular outcomes when combined with the current standard of care. We discuss the science of CETP inhibition, compare the CETP inhibitors developed (torcetrapib, evacetrapib, dalcetrapib, and anacetrapib), the findings from the CETP inhibitor trials, and the future outlook for CETP inhibitors in cholesterol modification.

scholarly journals Cholesteryl Ester Transfer Protein (CETP) Deficiency and CETP Inhibitors

2014 ◽  
Vol 37 (11) ◽  
pp. 777-784 ◽  
Author(s):  
Hiroshi Mabuchi ◽  
Atsushi Nohara ◽  
Akihiro Inazu
Keyword(s):  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Transfer Protein ◽  
Cetp Inhibitors

QSAR study of a series of cholesteryl ester transfer protein inhibitors

2011 ◽  
Vol 76 (7) ◽  
pp. 803-813 ◽  
Author(s):  
Mahesh T. Chhabria ◽  
Bhanubhai N. Suhagia ◽  
Appaji B. Mandhare ◽  
Pathik S. Brahmkshatriya
Keyword(s):  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Quantitative Structure Activity Relationship ◽  
Qsar Study ◽  
Transfer Protein ◽  
Cetp Inhibitors ◽  
Promising Target ◽  
Parabolic Relationship ◽  
Antihyperlipidemic Agents ◽  
Hdl Metabolism

Cholesteryl ester transfer protein (CETP), an enzyme which catalyses the transfer of cholesteryl ester from HDL to VLDL, is a promising target for discovery of novel antihyperlipidemic agents due to its pivotal role in HDL metabolism and reverse cholesterol transport. Quantitative structure activity relationship study of a series of CETP inhibitors was carried out using genetic function approximation to study various structural requirements for CETP inhibition. Various lipophilic, electronic, geometric and spatial descriptors were correlated with CETP inhibitory activity. Developed models were found predictive as indicated by their good r2pred values and satisfactory internal and external cross-validation results. Study reveals that lipophilicity (ClogP), with parabolic relationship, contributed significantly to the activity along with some electronic, geometric and quantum mechanical descriptors. The present study can be applied to future lead optimization of CETP inhibitors.

Synthesis and Molecular Modeling of Novel 3,5-Bis(trifluoromethyl)benzylamino Benzamides as Potential CETP Inhibitors

2021 ◽  
Vol 17 ◽  
Author(s):  
Reema Abu Khalaf ◽  
Mohammad Awad ◽  
Tariq Al-Qirim ◽  
Dima Sabbah
Keyword(s):  
Molecular Modeling ◽  
Cholesteryl Ester ◽  
Hdl Cholesterol ◽  
Biological Evaluation ◽  
Lead Compounds ◽  
Transfer Protein ◽  
Cetp Inhibitors ◽  
Good Target ◽  
Ic50 Values

Background: There is an alarming spread of cases of lipid-disorders in the world that occur due to harmful lifestyle habits, hereditary risk influences, or as a result of other illnesses or medicines. Cholesteryl ester transfer protein (CETP) is a 476-residue lipophilic glycoprotein that helps in the transport of cholesteryl ester and phospholipids from the atheroprotective HDL to the proatherogenic LDL and VLDL. Inhibition of CETP leads to elevation of HDL cholesterol and reduction of LDL cholesterol and triglycerides, so it's considered a good target for the treatment of hyperlipidemia and its comorbidities. Objectives: In this research synthesis, characterization, molecular modeling and biological evaluation of eight 3,5-bis(trifluoromethyl)benzylamino benzamides 9a-d and 10a-d were carried out. Methods: The synthesized molecules were characterized using 1H-NMR, 13C-NMR, IR and HR-MS. They were in vitro biologically tested to estimate their CETP inhibitory activity. Results: These compounds offered inhibitory effectiveness ranging from 42.2% to 100% at a concentration of 10 µM. Compounds bearing unsubstituted three aromatic rings (9a) or ortho-CF3 substituted (9b) were the most effective compounds among their analogs and showed IC50 values of 1.36 and 0.69 μM, respectively. The high docking scores of 9a-d and 10a-d against 4EWS imply that they might be possible CETP inhibitors. Pharmacophore mapping results demonstrate that the series approves the fingerprint of CETP active inhibitors and therefore explains their high binding affinity against CETP binding site. Conclusion: This work concludes that 3,5-bis(trifluoromethyl)benzylamino benzamides can serve as a promising CETP inhibitors lead compounds.

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