This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

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Name
Torcetrapib
Accession Number
DB06281
Type
Small Molecule
Groups
Investigational
Description

Torcetrapib (CP-529414, Pfizer) was developed to treat hypercholesterolemia but its development was halted in 2006 when phase III studies showed excessive mortality in the treatment group receiving a combination of atorvastatin and the study drug.

Structure
Thumb
Synonyms
Not Available
External IDs
CP 529,414 / CP-529,414 / CP-529414
Categories
UNII
4N4457MV2U
CAS number
262352-17-0
Weight
Average: 600.4733
Monoisotopic: 600.167061143
Chemical Formula
C26H25F9N2O4
InChI Key
CMSGWTNRGKRWGS-NQIIRXRSSA-N
InChI
InChI=1S/C26H25F9N2O4/c1-4-18-12-21(19-11-15(24(27,28)29)6-7-20(19)37(18)23(39)41-5-2)36(22(38)40-3)13-14-8-16(25(30,31)32)10-17(9-14)26(33,34)35/h6-11,18,21H,4-5,12-13H2,1-3H3/t18-,21+/m1/s1
IUPAC Name
ethyl (2R,4S)-4-({[3,5-bis(trifluoromethyl)phenyl]methyl}(methoxycarbonyl)amino)-2-ethyl-6-(trifluoromethyl)-1,2,3,4-tetrahydroquinoline-1-carboxylate
SMILES
CCOC(=O)N1[C@H](CC)C[C@H](N(CC2=CC(=CC(=C2)C(F)(F)F)C(F)(F)F)C(=O)OC)C2=C1C=CC(=C2)C(F)(F)F

Pharmacology

Indication

Investigated for use/treatment in peripheral vascular disease and hyperlipidemia.

Pharmacodynamics
Not Available
Mechanism of action

Torcetrapib is an inhibitor of cholesteryl ester-transfer protein (CETP) that increases high-density lipoprotein (HDL) cholesterol levels. The drug increases HDL-cholesterol and apolipoprotein A-I levels and decreases LDL-cholesterol and apolipoprotein B levels. The effect is showed in monotherapy and when administered in combination with statins.

TargetActionsOrganism
ACholesteryl ester transfer protein
antagonist
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Perez-Castrillon JL, Duenas-Laita A: New approaches to atherosclerotic cardiovascular disease. the potentialities of torcetrapib. Recent Pat Cardiovasc Drug Discov. 2006 Jan;1(1):109-14. [PubMed:18221079]
External Links
PubChem Compound
159325
ChemSpider
140123
BindingDB
50312718
ChEBI
49203
ChEMBL
CHEMBL479527
HET
0RP
Wikipedia
Torcetrapib
PDB Entries
4ews

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentCoronary Arteriosclerosis / Coronary Heart Disease (CHD) / Hyperlipidemias1
3CompletedTreatmentDyslipidemia (Fredrickson Type Ⅱa)1
3CompletedTreatmentDyslipidemia (Fredrickson Type Ⅱa) / Hyperlipidemias2
3CompletedTreatmentDyslipidemias / High Cholesterol / Hyperlipidemias1
3CompletedTreatmentHyperlipidemias3
3CompletedTreatmentHyperlipoproteinemia Type iv / Hypertriglyceridemias1
3TerminatedTreatmentCoronary Heart Disease (CHD) / Diabetes Mellitus (DM)1
3TerminatedTreatmentDyslipidemias / High Cholesterol / Hyperlipidemias1
3TerminatedTreatmentDyslipidemias / Hyperlipidemias1
3TerminatedTreatmentHyperlipoproteinemia Type III1
3TerminatedTreatmentMixed hypercholesterolemia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00589 mg/mLALOGPS
logP5.29ALOGPS
logP7.08ChemAxon
logS-5ALOGPS
pKa (Strongest Basic)-1.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area59.08 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity128.89 m3·mol-1ChemAxon
Polarizability50.67 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9282
Blood Brain Barrier+0.9624
Caco-2 permeable+0.5171
P-glycoprotein substrateSubstrate0.6547
P-glycoprotein inhibitor IInhibitor0.7607
P-glycoprotein inhibitor IIInhibitor0.8636
Renal organic cation transporterNon-inhibitor0.8158
CYP450 2C9 substrateNon-substrate0.8145
CYP450 2D6 substrateNon-substrate0.7812
CYP450 3A4 substrateSubstrate0.6575
CYP450 1A2 substrateNon-inhibitor0.6226
CYP450 2C9 inhibitorNon-inhibitor0.5507
CYP450 2D6 inhibitorNon-inhibitor0.8653
CYP450 2C19 inhibitorInhibitor0.6212
CYP450 3A4 inhibitorNon-inhibitor0.6518
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7998
Ames testNon AMES toxic0.607
CarcinogenicityNon-carcinogens0.7679
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7449 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9933
hERG inhibition (predictor II)Inhibitor0.6011
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as hydroquinolines. These are derivatives of quinoline in which in which at least one double bond in the quinoline moiety are reduced by adding two hydrogen atoms.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Hydroquinolines
Direct Parent
Hydroquinolines
Alternative Parents
Trifluoromethylbenzenes / Methylcarbamates / Organic carbonic acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organofluorides / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
show 1 more
Substituents
Tetrahydroquinoline / Trifluoromethylbenzene / Monocyclic benzene moiety / Benzenoid / Methylcarbamate / Carbamic acid ester / Carbonic acid derivative / Azacycle / Alkyl fluoride / Hydrocarbon derivative
show 11 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
carbamate ester, quinolines, (trifluoromethyl)benzenes (CHEBI:49203)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Triglyceride binding
Specific Function
Involved in the transfer of neutral lipids, including cholesteryl ester and triglyceride, among lipoprotein particles. Allows the net movement of cholesteryl ester from high density lipoproteins/HD...
Gene Name
CETP
Uniprot ID
P11597
Uniprot Name
Cholesteryl ester transfer protein
Molecular Weight
54755.74 Da
References
  1. Suckling K: The ENHANCE Study: an unusual publication of trial data raises questions beyond ezetimibe. Expert Opin Pharmacother. 2008 May;9(7):1067-70. doi: 10.1517/14656566.9.7.1067. [PubMed:18422466]
  2. Perez-Castrillon JL, Duenas-Laita A: New approaches to atherosclerotic cardiovascular disease. the potentialities of torcetrapib. Recent Pat Cardiovasc Drug Discov. 2006 Jan;1(1):109-14. [PubMed:18221079]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid 11-beta-monooxygenase activity
Specific Function
Preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone.
Gene Name
CYP11B2
Uniprot ID
P19099
Uniprot Name
Cytochrome P450 11B2, mitochondrial
Molecular Weight
57559.62 Da
References
  1. Hu X, Dietz JD, Xia C, Knight DR, Loging WT, Smith AH, Yuan H, Perry DA, Keiser J: Torcetrapib induces aldosterone and cortisol production by an intracellular calcium-mediated mechanism independently of cholesteryl ester transfer protein inhibition. Endocrinology. 2009 May;150(5):2211-9. doi: 10.1210/en.2008-1512. Epub 2009 Jan 22. [PubMed:19164467]

Drug created on March 19, 2008 10:21 / Updated on August 02, 2019 07:50