Ciluprevir

Identification

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Name
Ciluprevir
Accession Number
DB05868  (DB13130)
Type
Small Molecule
Groups
Investigational
Description

The compound, named BILN 2061, is an orally active inhibitor of the HCV NS3 protease and the first member of this new drug class to be tested in humans.

Structure
Thumb
Synonyms
Not Available
External IDs
BILN 2061 / BILN 2061 ZW
Categories
UNII
75C8DU40T0
CAS number
300832-84-2
Weight
Average: 774.925
Monoisotopic: 774.341083296
Chemical Formula
C40H50N6O8S
InChI Key
PJZPDFUUXKKDNB-KNINVFKUSA-N
InChI
InChI=1S/C40H50N6O8S/c1-23(2)41-38-43-32(22-55-38)31-19-34(28-16-15-26(52-3)17-30(28)42-31)53-27-18-33-35(47)45-40(37(49)50)20-24(40)11-7-5-4-6-8-14-29(36(48)46(33)21-27)44-39(51)54-25-12-9-10-13-25/h7,11,15-17,19,22-25,27,29,33H,4-6,8-10,12-14,18,20-21H2,1-3H3,(H,41,43)(H,44,51)(H,45,47)(H,49,50)/b11-7-/t24-,27-,29+,33+,40-/m1/s1
IUPAC Name
(1S,4R,6S,7Z,14S,18R)-14-{[(cyclopentyloxy)carbonyl]amino}-18-[(7-methoxy-2-{2-[(propan-2-yl)amino]-1,3-thiazol-4-yl}quinolin-4-yl)oxy]-2,15-dioxo-3,16-diazatricyclo[14.3.0.0⁴,⁶]nonadec-7-ene-4-carboxylic acid
SMILES
COC1=CC2=C(C=C1)C(O[C@H]1CN3C(=O)[C@H](CCCCC\C=C/[C@]4([H])C[C@@]4(C(O)=O)NC(=O)[C@]3([H])C1)NC(=O)OC1CCCC1)=CC(=N2)C1=CSC(NC(C)C)=N1

Pharmacology

Indication

Investigated for use/treatment in hepatitis (viral, C).

Pharmacodynamics
Not Available
Mechanism of action

A distinguishing feature of the BILN 2061 inhibitor series is the presence of C-terminal carboxylic acid functionality. This provides exquisite selectivity with respect to other proteases, a property not easily attained with more conventional classes of covalent, reversible serine protease inhibitors. BILN 2061 blocks NS3 protease-dependent polyprotein processing in HCV replicon-containing cells. It is orally bioavailable in various animal species.

TargetActionsOrganism
UGenome polyproteinNot Available
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. Vanwolleghem T, Meuleman P, Libbrecht L, Roskams T, De Vos R, Leroux-Roels G: Ultra-rapid cardiotoxicity of the hepatitis C virus protease inhibitor BILN 2061 in the urokinase-type plasminogen activator mouse. Gastroenterology. 2007 Oct;133(4):1144-55. Epub 2007 Jul 10. [PubMed:17919490]
External Links
PubChem Compound
9853710
PubChem Substance
175427047
ChemSpider
8029420
BindingDB
50142916
ChEMBL
CHEMBL297884
Wikipedia
Protease_inhibitor_%28pharmacology%29

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Liver Cirrhosis1

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 Solubility0.00288 mg/mLALOGPS
logP4.43ALOGPS
logP5.32ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)3.73ChemAxon
pKa (Strongest Basic)2.37ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area181.31 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity204.13 m3·mol-1ChemAxon
Polarizability82.31 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.69
Blood Brain Barrier-0.985
Caco-2 permeable-0.6969
P-glycoprotein substrateSubstrate0.8509
P-glycoprotein inhibitor IInhibitor0.6345
P-glycoprotein inhibitor IINon-inhibitor0.7165
Renal organic cation transporterNon-inhibitor0.9204
CYP450 2C9 substrateNon-substrate0.719
CYP450 2D6 substrateNon-substrate0.7731
CYP450 3A4 substrateSubstrate0.7173
CYP450 1A2 substrateNon-inhibitor0.7649
CYP450 2C9 inhibitorNon-inhibitor0.5721
CYP450 2D6 inhibitorNon-inhibitor0.8385
CYP450 2C19 inhibitorNon-inhibitor0.5
CYP450 3A4 inhibitorInhibitor0.5355
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6419
Ames testNon AMES toxic0.6693
CarcinogenicityNon-carcinogens0.877
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6030 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9765
hERG inhibition (predictor II)Inhibitor0.5447
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 cyclic peptides. These are compounds containing a cyclic moiety bearing a peptide backbone.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Cyclic peptides
Alternative Parents
Macrolactams / Alpha amino acids and derivatives / Quinolines and derivatives / Anisoles / Secondary alkylarylamines / Alkyl aryl ethers / 2,4-disubstituted thiazoles / Cyclopropanecarboxylic acids / Pyridines and derivatives / 2-amino-1,3-thiazoles
show 15 more
Substituents
Cyclic alpha peptide / Macrolactam / Alpha-amino acid or derivatives / Quinoline / Anisole / 2,4-disubstituted 1,3-thiazole / Alkyl aryl ether / Secondary aliphatic/aromatic amine / Cyclopropanecarboxylic acid or derivatives / Cyclopropanecarboxylic acid
show 31 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Not Available
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regula...
Gene Name
Not Available
Uniprot ID
P26664
Uniprot Name
Genome polyprotein
Molecular Weight
327198.77 Da

Drug created on November 18, 2007 11:28 / Updated on June 04, 2019 06:20