胆固醇酯转移蛋白的取代联苯恶唑烷酮抑制剂的发现。
Discovery of substituted biphenyl oxazolidinone inhibitors of cholesteryl ester transfer protein.
作者信息
Thompson Christopher F, Ali Amjad, Quraishi Nazia, Lu Zhijian, Hammond Milton L, Sinclair Peter J, Anderson Matt S, Eveland Suzanne S, Guo Qiu, Hyland Sheryl A, Milot Denise P, Sparrow Carl P, Wright Samuel D
机构信息
Departments of Medicinal Chemistry and Cardiovascular Diseases, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
出版信息
ACS Med Chem Lett. 2011 Mar 24;2(6):424-7. doi: 10.1021/ml100309n. eCollection 2011 Jun 9.
Abstract
Recently, there has been a strong interest in the ability to increase levels of high density lipoprotein-cholesterol (HDL-C). This interest stems from the hypothesis that such an elevation in HDL-C will decrease the likelihood of cardiovascular disease. Inhibition of cholesteryl ester transfer protein (CETP) has been shown to elevate HDL-C levels in human subjects. This letter describes the discovery of a novel and potent (<100 nM IC50 for the inhibition of CE transfer) CETP inhibitor scaffold containing an oxazolidinone core.
摘要
最近，人们对提高高密度脂蛋白胆固醇（HDL-C）水平的能力产生了浓厚兴趣。这种兴趣源于这样一种假设，即HDL-C的这种升高将降低心血管疾病的可能性。已证明抑制胆固醇酯转移蛋白（CETP）可提高人体受试者的HDL-C水平。这封信描述了一种新型强效（抑制CE转移的IC50<100 nM）CETP抑制剂支架的发现，该支架含有恶唑烷酮核心。
相似文献
1
Discovery of substituted biphenyl oxazolidinone inhibitors of cholesteryl ester transfer protein.胆固醇酯转移蛋白的取代联苯恶唑烷酮抑制剂的发现。
ACS Med Chem Lett. 2011 Mar 24;2(6):424-7. doi: 10.1021/ml100309n. eCollection 2011 Jun 9.
2
On- and off-target pharmacology of torcetrapib: current understanding and implications for the structure activity relationships (SAR), discovery and development of cholesteryl ester-transfer protein (CETP) inhibitors.托彻普的靶标和非靶标药理学：当前的认识及其对结构-活性关系（SAR）、胆固醇酯转移蛋白（CETP）抑制剂的发现和开发的影响。
Drugs. 2012 Mar 5;72(4):491-507. doi: 10.2165/11599310-000000000-00000.
3
Absence of cholesteryl ester transfer protein-mediated cholesteryl ester mass transfer from high-density lipoprotein to low-density lipoprotein particles is a major feature of combined hyperlipidaemia.胆固醇酯转移蛋白介导的胆固醇酯从高密度脂蛋白到低密度脂蛋白颗粒的质量转移缺失是混合性高脂血症的一个主要特征。
Eur J Clin Invest. 1996 Jun;26(6):485-94. doi: 10.1046/j.1365-2362.1996.168318.x.
4
Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors.胆固醇酯转移蛋白：他汀类药物、贝特类药物、烟酸和胆固醇酯转移蛋白抑制剂调脂治疗作用的核心。
Eur Heart J. 2010 Jan;31(2):149-64. doi: 10.1093/eurheartj/ehp399. Epub 2009 Oct 12.
5
Future of cholesteryl ester transfer protein (CETP) inhibitors: a pharmacological perspective.CETP 抑制剂的未来：药理学视角。
Clin Pharmacokinet. 2013 Aug;52(8):615-26. doi: 10.1007/s40262-013-0071-8.
6
Effect of inhibiting cholesteryl ester transfer protein on the kinetics of high-density lipoprotein cholesteryl ester transport in plasma: in vivo studies in rabbits.抑制胆固醇酯转运蛋白对血浆中高密度脂蛋白胆固醇酯转运动力学的影响：家兔体内研究
Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):884-90. doi: 10.1161/01.ATV.0000201064.89581.35. Epub 2005 Dec 22.
7
8
Inhibition of cholesteryl ester transfer protein increases cholesteryl ester content of large HDL independently of HDL-to-HDL homotypic transfer: in vitro vs in vivo comparison using anacetrapib and dalcetrapib.抑制胆固醇酯转运蛋白可增加大型高密度脂蛋白（HDL）的胆固醇酯含量，且与HDL间的同型转运无关：使用阿那曲匹和达塞曲匹进行的体外与体内比较
Eur J Pharmacol. 2015 Sep 5;762:256-62. doi: 10.1016/j.ejphar.2015.05.061. Epub 2015 Jun 3.
9
Cholesteryl ester transfer protein: An enigmatic pharmacology - Antagonists and agonists.胆固醇酯转移蛋白：药理学中的未解之谜——拮抗剂和激动剂。
Atherosclerosis. 2018 Nov;278:286-298. doi: 10.1016/j.atherosclerosis.2018.09.035. Epub 2018 Oct 1.
10
Pharmacological modulation of cholesteryl ester transfer protein, a new therapeutic target in atherogenic dyslipidemia.胆固醇酯转运蛋白的药理学调节，动脉粥样硬化性血脂异常的新治疗靶点。
Pharmacol Ther. 2004 Jan;101(1):17-38. doi: 10.1016/j.pharmthera.2003.10.001.
引用本文的文献
1
Oxazolidinones as versatile scaffolds in medicinal chemistry.恶唑烷酮类化合物作为药物化学中用途广泛的骨架。
RSC Med Chem. 2023 Feb 8;14(5):823-847. doi: 10.1039/d2md00415a. eCollection 2023 May 25.
本文引用的文献
1
Safety of anacetrapib in patients with or at high risk for coronary heart disease.在有或有高冠心病风险的患者中安塞曲匹的安全性。
N Engl J Med. 2010 Dec 16;363(25):2406-15. doi: 10.1056/NEJMoa1009744. Epub 2010 Nov 17.
2
Design of a novel class of biphenyl CETP inhibitors.设计一类新型联苯 CETP 抑制剂。
Bioorg Med Chem Lett. 2010 Dec 15;20(24):7469-72. doi: 10.1016/j.bmcl.2010.10.019. Epub 2010 Oct 15.
3
Cholesteryl ester transfer protein (CETP) inhibitors.胆固醇酯转运蛋白（CETP）抑制剂
Curr Top Med Chem. 2009;9(5):419-27. doi: 10.2174/156802609788340823.
4
HDL: still a target for new therapies?高密度脂蛋白：仍然是新疗法的靶点吗？
Curr Opin Investig Drugs. 2008 Sep;9(9):950-6.
5
Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone.托彻普（torcetrapib）引起的血压升高与胆固醇酯转运蛋白（CETP）抑制无关，且伴有醛固酮循环水平升高。
Br J Pharmacol. 2008 Aug;154(7):1465-73. doi: 10.1038/bjp.2008.229. Epub 2008 Jun 9.
6
Illuminating HDL--is it still a viable therapeutic target?解读高密度脂蛋白——它仍是一个可行的治疗靶点吗？
N Engl J Med. 2007 Nov 22;357(21):2180-3. doi: 10.1056/NEJMe0707210. Epub 2007 Nov 5.
7
Effects of torcetrapib in patients at high risk for coronary events.托彻普对冠心病高危患者的影响。
N Engl J Med. 2007 Nov 22;357(21):2109-22. doi: 10.1056/NEJMoa0706628. Epub 2007 Nov 5.
8
A high-precision fluorogenic cholesteryl ester transfer protein assay compatible with animal serum and 3456-well assay technology.一种与动物血清兼容的高精度荧光胆固醇酯转移蛋白检测方法及3456孔检测技术。
Anal Biochem. 2007 Sep 15;368(2):239-49. doi: 10.1016/j.ab.2007.06.003. Epub 2007 Jun 8.
9
The potential for CETP inhibition to reduce cardiovascular disease risk.抑制胆固醇酯转运蛋白（CETP）降低心血管疾病风险的可能性。
Curr Med Res Opin. 2006 Dec;22(12):2467-78. doi: 10.1185/030079906X148634.
10
Mechanisms of disease: HDL metabolism as a target for novel therapies.疾病机制：作为新型治疗靶点的高密度脂蛋白代谢
Nat Clin Pract Cardiovasc Med. 2007 Feb;4(2):102-9. doi: 10.1038/ncpcardio0768.
Zotero 插件