875446-37-0Relevant academic research and scientific papers
Invention of MK-8262, a Cholesteryl Ester Transfer Protein (CETP) Inhibitor Backup to Anacetrapib with Best-in-Class Properties ()
Vachal, Petr,Duffy, Joseph L.,Campeau, Louis-Charles,Amin, Rupesh P.,Mitra, Kaushik,Murphy, Beth Ann,Shao, Pengcheng P.,Sinclair, Peter J.,Ye, Feng,Katipally, Revathi,Lu, Zhijian,Ondeyka, Debra,Chen, Yi-Heng,Zhao, Kake,Sun, Wanying,Tyagarajan, Sriram,Bao, Jianming,Wang, Sheng-Ping,Cote, Josee,Lipardi, Concetta,Metzger, Daniel,Leung, Dennis,Hartmann, Georgy,Wollenberg, Gordon K.,Liu, Jian,Tan, Lushi,Xu, Yingju,Chen, Qinghao,Liu, Guiquan,Blaustein, Robert O.,Johns, Douglas G.
, p. 13215 - 13258 (2021/09/02)
Cholesteryl ester transfer protein (CETP) represents one of the key regulators of the homeostasis of lipid particles, including high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles. Epidemiological evidence correlates increased HDL and decreased LDL to coronary heart disease (CHD) risk reduction. This relationship is consistent with a clinical outcomes trial of a CETP inhibitor (anacetrapib) combined with standard of care (statin), which led to a 9% additional risk reduction compared to standard of care alone. We discuss here the discovery of MK-8262, a CETP inhibitor with the potential for being the best-in-class molecule. Novel in vitro and in vivo paradigms were integrated to drug discovery to guide optimization informed by a critical understanding of key clinical adverse effect profiles. We present preclinical and clinical evidence of MK-8262 safety and efficacy by means of HDL increase and LDL reduction as biomarkers for reduced CHD risk.
Preparation method of Anacetrapib
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Paragraph 0041; 0053; 0054, (2017/08/28)
The invention provides a preparation method of Anacetrapib. The method includes: firstly subjecting a compound 1 to ylide reaction to obtain olefin, and then carrying out epoxidation to obtain a compound 2; then, reacting the compound 2 with a compound 3 in a solvent to prepare a compound 4, finally subjecting the compound 4 to condensation reaction to obtain a compound 5, and conducting deprotection cyclization on the compound 5 so as to obtain a compound 6 Anacetrapib. The operation method provided by the invention is simple, has low requirement for water in the reaction system, is low in process cost, and is suitable for industrial application.
Preparation method of Anacetrapib
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, (2017/07/20)
The invention relates to a preparation method of a compound represented by the formula (I). The preparation method comprises the following steps: (1) reacting 2-chloro-5-trifluoromethyl-aniline (II) with (4-fluoro-5-isopropyl-2-methoxyphenyl)boric acid (III) to obtain 2-(4-fluoro-5-isopropyl-20methoxyphenyl)-5-trifluoromethyl-aniline (formula IV); (2) reacting the compound (formula IV) with tert-butyl nitrite, acetaldehyde, and alkalis to obtain 2-(4-fluoro-5-isopropyl-2-methoxyphenyl)-5-trifluoromethyl-benzyl alcohol (formula V); (3) reacting the compound (formula V) with a halogenation reagent, and then adding (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidine-2-one (VI) into the reaction mixture to carry out reactions so as to obtain (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[4'-fluoro-5'-isoproypyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidine-2-one represented by the formula (I), namely Anacetrapib.
CATALYST AND METHOD FOR PRODUCING OPTICALLY ACTIVE ANTI-1,2-NITROALKANOL COMPOUND
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, (2016/01/12)
A catalyst, which is obtained by mixing a compound expressed by the following Structural Formula (1), a nitroalkane compound, a neodymium-containing compound, a sodium-containing compound, and a carbon structure:
PROCESS FOR PREPARATION OF ANACETRAPIB AND INTERMEDIATES THEREOF
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, (2014/08/06)
The present invention relates to a novel process for the preparation of anacetrapib. The present invention also relates to novel intermediate or its salt and its use in the preparation of anacetrapib.
Process for a CETP Inhibitor
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, (2014/10/16)
An efficient process is disclosed for producing the compound of formula I, which is the CETP inhibitor anacetrapib, which raises HDL-cholesterol and reduces LDL-cholesterol in human patients and may be effective for treating or reducing the risk of developing atherosclerosis:
SYNTHESIS OF INTERMEDIATES FOR PREPARING ANACETRAPIB AND DERIVATIVES THEREOF
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, (2013/07/05)
The present invention relates to the field of organic chemistry, more specifically to the synthesis of intermediate compounds which can be used in the synthesis of pharmaceutically active agents such as anacetrapib or derivatives thereof.
Self-assembling neodymium/sodium heterobimetallic asymmetric catalyst confined in a carbon nanotube network
Ogawa, Takanori,Kumagai, Naoya,Shibasaki, Masakatsu
, p. 6196 - 6201 (2013/07/19)
Confined cat works better: A self-assembling heterobimetallic catalyst, comprised of a Nd/Na/amide ligand confined in an entangled multiwalled carbon nanotube (MWNT) network, outperforms the unconfined catalyst in anti-selective catalytic asymmetric nitroaldol reactions. The confined catalyst could be used repeatedly through simple filtration, and was applied to a concise enantioselective synthesis of anacetrapib. Copyright
PROCESS FOR A CETP INHIBITOR
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, (2013/05/22)
An efficient process is disclosed for producing the compound of formula I, which is the CETP inhibitor anacetrapib, which raises HDL-cholesterol and reduces LDL-cholesterol in human patients and may be effective for treating or reducing the risk of developing atherosclerosis:.
SYNTHESIS OF INTERMEDIATES FOR PREPARING ANACETRAPIB AND DERIVATIVES THEREOF
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, (2012/07/13)
The present invention relates to the field of organic chemistry, more specifically to the synthesis of intermediate compounds which can be used in the synthesis of pharmaceutically active agents such as anacetrapib or derivatives thereof.
