evacetrapib

{{Chembox

| Verifiedfields = changed

| verifiedrevid = 461280529

| ImageFile=Evacetrapib.svg

| ImageSize=150px

| IUPACName=Trans-4-({(5S)-5-[{[3,5-bis(trifluoromethyl)phenyl]methyl}(2-methyl-2H-tetrazol-5- yl)amino]-7,9-dimethyl-2,3,4,5-tetrahydro-1H-benzazepin-1-yl}methyl) cyclohexanecarboxylic acid

| OtherNames = LY2484595

|Section1={{Chembox Identifiers

| CASNo=1186486-62-3

| CASNo_Ref = {{cascite|correct|??}}

| PubChem = 49836058

| KEGG = D10121

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 2017179

| UNII = 51XWV9K850

| UNII_Ref = {{fdacite|correct|FDA}}

| KEGG_Ref = {{keggcite|correct|kegg}}

| SMILES = O=C([C@H]1CC[C@H](CN2CCC[C@H](N(CC3=CC(C(F)(F)F)=CC(C(F)(F)F)=C3)C4=NN(C)N=N4)C5=CC(C)=CC(C)=C52)CC1)O

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 26286916

| InChI = 1/C31H36F6N6O2/c1-18-11-19(2)27-25(12-18)26(5-4-10-42(27)16-20-6-8-22(9-7-20)28(44)45)43(29-38-40-41(3)39-29)17-21-13-23(30(32,33)34)15-24(14-21)31(35,36)37/h11-15,20,22,26H,4-10,16-17H2,1-3H3,(H,44,45)/t20-,22-,26-/m0/s1

| InChIKey = IHIUGIVXARLYHP-YBXDKENTBY

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C31H36F6N6O2/c1-18-11-19(2)27-25(12-18)26(5-4-10-42(27)16-20-6-8-22(9-7-20)28(44)45)43(29-38-40-41(3)39-29)17-21-13-23(30(32,33)34)15-24(14-21)31(35,36)37/h11-15,20,22,26H,4-10,16-17H2,1-3H3,(H,44,45)/t20-,22-,26-/m0/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = IHIUGIVXARLYHP-YBXDKENTSA-N

}}

|Section2={{Chembox Properties

| C=31 | H=36 | F=6 | N=6 | O=2

| Appearance =

| Density =

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|Section3={{Chembox Hazards

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Evacetrapib was a drug under development by Eli Lilly and Company (investigational name LY2484595) that inhibits cholesterylester transfer protein (CETP inhibitor). CETP collects triglycerides from very low-density lipoproteins (VLDL) or low-density lipoproteins (LDL) and exchanges them for cholesteryl esters from high-density lipoproteins (HDL), and vice versa, but primarily increasing high-density lipoprotein and lowering low-density lipoprotein. It is thought that modifying lipoprotein levels modifies the risk of cardiovascular disease. The first CETP inhibitor, torcetrapib, was unsuccessful because it increased levels of the hormone aldosterone and increased blood pressure, which led to excess cardiac events when it was studied. Evacetrapib does not have the same effect.{{cite journal |vauthors=Cao G, Beyer TP, Zhang Y |title=Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that elevates HDL cholesterol without inducing aldosterone or increasing blood pressure |journal=J. Lipid Res. |volume=52 |issue=12 |pages=2169–76 |date=December 2011 |pmid=21957197 |doi=10.1194/jlr.M018069 |doi-access=free |pmc=3220285|display-authors=etal}} When studied in a small clinical trial in people with elevated LDL and low HDL, significant improvements were noted in their lipid profile.{{cite journal |vauthors=Nicholls SJ, Brewer HB, Kastelein JJ, Krueger KA, Wang MD, Shao M, Hu B, McErlean E, Nissen SE | title=Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol | journal=JAMA | year=2011 | volume=306 | issue=19 | pages=2099–109 | doi=10.1001/jama.2011.1649| pmid=22089718 | doi-access= }}

Evacetrapib evaluation for treatment of high-risk vascular disease was discontinued due to lack of efficacy, as had already happened in the past with two other CETP inhibitors (torcetrapib and dalcetrapib{{cite journal |author=Schwartz GG |title=Effects of dalcetrapib in patients with a recent acute coronary syndrome. |journal=N Engl J Med |volume=367 |issue=22 |pages=2089–99 |date=Nov 2015 |pmid=23126252|display-authors=etal |doi=10.1056/NEJMoa1206797|url=http://www.zora.uzh.ch/75761/1/NEJMoa1206797.pdf }}) due to increased deaths and little identifiable cardiovascular benefit (despite substantial increases in HDL). Some hypothesize that CETP inhibitors may still be useful in the treatment of dyslipidemia, though significant caution is warranted.{{cite journal |vauthors=Joy T, Hegele RA |title=The end of the road for CETP inhibitors after torcetrapib? |journal=Curr. Opin. Cardiol. |volume=24 |issue=4 |pages=364–71 |date=July 2009 |pmid=19522058 |doi=10.1097/HCO.0b013e32832ac166|s2cid=6965741 }} Anacetrapib is the fourth CETP inhibitor being tried for cardiovascular benefit