1186486-62-3

Basic information

• Product Name: LY-2484595
• Synonyms: LY-2484595;Evacetrapib;trans-4-[[(5S)-5-[[[3,5-Bis(trifluoromethyl)phenyl]methyl](2-methyl-2H-tetrazol-5-yl)amino]-2,3,4,5-tetrahydro-7,9-dimethyl-1H-1-benzazepin-1-yl]methyl]cyclohexanecarboxylic acid;(1S,4r)-4-(((S)-5-((3,5-bis(trifluoroMethyl)benzyl)(2-Methyl-2H-tetrazol-5-yl)aMino)-7,9-diMethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)Methyl)cyclohexanecarboxylic acid;Evacetrapib (LY2484595);Cyclohexanecarboxylic acid, 4-[[(5S)-5-[[[3,5-bis(trifluoroMethyl)phenyl]Methyl](2-Methyl-2H-tetrazol-5-yl)aMino]-2,3,4,5-tetrahydro-7,9-diMethyl-1H-1-benzazepin-1-yl]Methyl]-, trans-;Evacetrapib, >=98%;(1S,4r)-4-(((S)-5-((3,5-Bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)-7,9-dimet
• CAS NO: 1186486-62-3
• Molecular Formula: C₃₁H₃₆F₆N₆O₂
• Molecular Weight: 638.66
• Product Categories: Inhibitor;Inhibitors
• Mol File: 1186486-62-3.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 680.1±65.0 °C(Predicted)
• Appearance: /
• Density: 1.40
• Solubility: ≥32.1 mg/mL in DMSO; insoluble in H2O; ≥50.4 mg/mL in EtOH with ultrasonic
• PKA: 4.73±0.10(Predicted)
• CAS DataBase Reference: LY-2484595(CAS DataBase Reference)
• NIST Chemistry Reference: LY-2484595(1186486-62-3)
• EPA Substance Registry System: LY-2484595(1186486-62-3)

Safety Data

• Hazardous Substances Data: 1186486-62-3(Hazardous Substances Data)

Usage

Uses

Evacetrapib is an inhibitor of?cholesteryl ester transfer protein (CETP). CETP catalyzes the exchange of cholesteryl ester and triglyceride between lipoproteins and modulates HDL cholesterol levels in plasma. CETP inhibitors are potential compounds for treating coronary artery disease.

Biological Activity

evacetrapib is a potent and selective inhibitor of cholesteryl ester transfer protein (cetp) with ic50 value of 5.5nm [1].as a benzazepine-based inhibitor of cetp, evacetrapib is developed to increase hdl cholesterol for the treatment of coronary artery disease. evacetrapib is efficacious both in vitro and in vivo. the ic50 values of evacetrapib against cetp are 5.5nm and 26nm, respectively in the buffer assay using human recombinant cetp and in the plasma assay using human plasma cetp. in the animal model of human cetp/apoai double transgenic mouse line, oral administration of evacetrapib at 30mg/kg significantly inhibits the cetp activity as well as increases the level of hdl. besides that, the ed50 value of evacetrapib is less than 5mg/kg. compared to the previous inhibitors of cetp, evacetrapib has less side effects. it is found no to increase blood pressure zucker diabetic fatty rats and not to induce aldosterone or cortisol synthesis in h295r cells [1].

references

[1] cao g, beyer tp, zhang y, schmidt rj, chen yq, cockerham sl, zimmerman km, karathanasis sk, cannady ea, fields t, mantlo nb. evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that elevates hdl cholesterol without inducing aldosterone or increasing blood pressure. j lipid res. 2011 dec;52(12):2169-76.

Relevant articles and documents

Development of a hydrogenative reductive amination for the synthesis of evacetrapib: Unexpected benefits of water

For the synthesis of cholesteryl ester transfer protein (CETP) inhibitor evacetrapib, a hydrogenative reductive amination was chosen to join the substituted cyclohexyl subunit to the benzazepine core. The addition of water, which suppressed undesired epimerization without affecting the rate of product formation, was key to the reactions success. The process was scaled to produce more than 1100 kg of material.