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Details

Stereochemistry ABSOLUTE
Molecular Formula C31H36F6N6O2
Molecular Weight 638.647
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of EVACETRAPIB

SMILES

CN1N=NC(=N1)N(CC2=CC(=CC(=C2)C(F)(F)F)C(F)(F)F)[C@H]3CCCN(C[C@H]4CC[C@@H](CC4)C(O)=O)C5=C3C=C(C)C=C5C

InChI

InChIKey=IHIUGIVXARLYHP-YBXDKENTSA-N
InChI=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

HIDE SMILES / InChI
Molecular Formula C31H36F6N6O2
Molecular Weight 638.647
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including http://www.selleckchem.com/products/evacetrapib-ly2484595.html

Evacetrapib (LY2484595) is a novel benzazepine-based CETP inhibitor that has been developed at Lilly Research Laboratories. Evacetrapib inhibits CETP with IC50 of 5.5 nM, elevates HDL cholesterol without increases in aldosterone or blood pressure. Phase 3. On 01 Sep 2016 Eli Lilly terminates the phase III ACCENTUATE trial in Hyperlipidaemia (Adjunctive treatment) in USA and Puerto Rico (PO) due to insufficient efficacy (NCT02227784).

Originator

Eli Lilly
237
Curator's Comment: # Eli Lilly

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 5.5 nM [IC50]
Inhibitor
8297
 0.57 µM [Ki]
Inhibitor
8297
 1.2 µM [Ki]
Inhibitor
8297
 2.1 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
656
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1330 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/24961753
600 mg 1 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
EVACETRAPIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: LOW-FAT
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
13700 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/24961753
600 mg 1 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
EVACETRAPIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: LOW-FAT
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
37.4 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/24961753
600 mg 1 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
EVACETRAPIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: LOW-FAT
Doses

Doses

DosePopulationAdverse events​
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24271137
Page: p.287
healthy, ADULT
n = 70
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 70
Sources:
https://pubmed.ncbi.nlm.nih.gov/24271137
Page: p.287
Disc. AE: Deep vein thrombosis leg...
AEs leading to
discontinuation/dose reduction:
Deep vein thrombosis leg (1.4%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/24271137
Page: p.287
600 mg 1 times / day multiple, oral
Studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24961753
Page: p.1582
healthy, ADULT
n = 25
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: LOW-FAT
Population Size: 25
Sources:
https://pubmed.ncbi.nlm.nih.gov/24961753
Page: p.1582
Disc. AE: Skin rash...
AEs leading to
discontinuation/dose reduction:
Skin rash (8%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/24961753
Page: p.1582
AEs

AEs

AESignificanceDosePopulation
Deep vein thrombosis leg 1.4%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24271137
Page: p.287
healthy, ADULT
n = 70
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 70
Sources:
https://pubmed.ncbi.nlm.nih.gov/24271137
Page: p.287
Skin rash 8%
Disc. AE
600 mg 1 times / day multiple, oral
Studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24961753
Page: p.1582
healthy, ADULT
n = 25
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: LOW-FAT
Population Size: 25
Sources:
https://pubmed.ncbi.nlm.nih.gov/24961753
Page: p.1582
PubMed

PubMed

TitleDatePubMed
Design, synthesis and structure-activity-relationship of 1,5-tetrahydronaphthyridines as CETP inhibitors.
2012 May 1
Future of cholesteryl ester transfer protein inhibitors.
2014
Recent advances in pharmacotherapy for hypertriglyceridemia.
2014 Oct
Patents

Patents

08299060
2
08329688
2
20100331309
2
20120058990
2
8299060
2
8329688
2

Sample Use Guides

In Vivo Use Guide
Evacetrapib 130 mg tablet, administered orally once , daily for up to 4 years.
Route of Administration: Oral
In Vitro Use Guide
Evacetrapib inhibited human recombinant CETP protein (5.5 nM IC(50)) and CETP activity in human plasma (36 nM IC(50)) in vitro.
Substance Class Chemical
Created
by admin
on Fri Dec 15 22:10:37 GMT 2023
Edited
by admin
on Fri Dec 15 22:10:37 GMT 2023
Record UNII
51XWV9K850
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
EVACETRAPIB
INN   MI   USAN   WHO-DD  
USAN   INN  
Official Name English
EVACETRAPIB [USAN]
Common Name English
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
Common Name English
LY-2484595
Code English
LY2484595
Code English
(1R,4R)-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-1-BENZAZEPIN-1-YL)METHYL)CYCLOHEXANE-1-CARBOXYLIC ACID
Common Name English
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-
Common Name English
evacetrapib [INN]
Common Name English
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-
Common Name English
EVACETRAPIB [MI]
Common Name English
Evacetrapib [WHO-DD]
Common Name English
Code System Code Type Description
WIKIPEDIA
EVACETRAPIB
Created by admin on Fri Dec 15 22:10:37 GMT 2023 , Edited by admin on Fri Dec 15 22:10:37 GMT 2023
PRIMARY
DRUG BANK
DB11655
Created by admin on Fri Dec 15 22:10:37 GMT 2023 , Edited by admin on Fri Dec 15 22:10:37 GMT 2023
PRIMARY
NCI_THESAURUS
C166804
Created by admin on Fri Dec 15 22:10:37 GMT 2023 , Edited by admin on Fri Dec 15 22:10:37 GMT 2023
PRIMARY
CAS
1186486-62-3
Created by admin on Fri Dec 15 22:10:37 GMT 2023 , Edited by admin on Fri Dec 15 22:10:37 GMT 2023
PRIMARY
EVMPD
SUB189015
Created by admin on Fri Dec 15 22:10:37 GMT 2023 , Edited by admin on Fri Dec 15 22:10:37 GMT 2023
PRIMARY
ChEMBL
CHEMBL2017179
Created by admin on Fri Dec 15 22:10:37 GMT 2023 , Edited by admin on Fri Dec 15 22:10:37 GMT 2023
PRIMARY
EPA CompTox
DTXSID801026275
Created by admin on Fri Dec 15 22:10:37 GMT 2023 , Edited by admin on Fri Dec 15 22:10:37 GMT 2023
PRIMARY
SMS_ID
100000174866
Created by admin on Fri Dec 15 22:10:37 GMT 2023 , Edited by admin on Fri Dec 15 22:10:37 GMT 2023
PRIMARY
FDA UNII
51XWV9K850
Created by admin on Fri Dec 15 22:10:37 GMT 2023 , Edited by admin on Fri Dec 15 22:10:37 GMT 2023
PRIMARY
MERCK INDEX
m5217
Created by admin on Fri Dec 15 22:10:37 GMT 2023 , Edited by admin on Fri Dec 15 22:10:37 GMT 2023
PRIMARY Merck Index
USAN
XX-71
Created by admin on Fri Dec 15 22:10:37 GMT 2023 , Edited by admin on Fri Dec 15 22:10:37 GMT 2023
PRIMARY
INN
9442
Created by admin on Fri Dec 15 22:10:37 GMT 2023 , Edited by admin on Fri Dec 15 22:10:37 GMT 2023
PRIMARY
Related Record Type Details
Structure of EVACETRAPIB MONOHYDRATE
SALT/SOLVATE -> PARENT
Structure of EVACETRAPIB MONOHYDRATE
SOLVATE->ANHYDROUS
CHOLESTERYL ESTER TRANSFER PROTEIN
TARGET -> INHIBITOR
Evacetrapib did not impact aldosterone levels or blood pressure, even while achieving more substantial modulation of HDL and LDL levels than torcetrapib. Unfortunately, it also did not offer clinical benefit in terms of reducing CV events and has been discontinued.
Related Record Type Details
Structure of EVACETRAPIB
ACTIVE MOIETY
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