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

Identification

Name
Vicriviroc
Accession Number
DB06652
Type
Small Molecule
Groups
Investigational
Description

Vicriviroc, previously named SCH 417690 and SCH-D, is a pyrimidine currently undergoing clinical trials as a CCR5 entry inhibitor of HIV-1. It was developed by the pharmaceutical company Schering-Plough.

Structure
Thumb
Synonyms
Not Available
External IDs
MK-4176 / SCH 417690 / SCH-417690 / SCH-D
Product Ingredients
IngredientUNIICASInChI Key
Vicriviroc Hydrochloride25SS1WQB7W541503-48-4ULGCLTGMZKAFMX-RIAYWLAYSA-N
Vicriviroc MaleateEP3QG127N9599179-03-0GXINKQQWHLIBJA-UCIBKFKQSA-N
Categories
UNII
TL515DW4QS
CAS number
306296-47-9
Weight
Average: 533.6288
Monoisotopic: 533.2977601
Chemical Formula
C28H38F3N5O2
InChI Key
CNPVJJQCETWNEU-CYFREDJKSA-N
InChI
InChI=1S/C28H38F3N5O2/c1-19-16-35(14-15-36(19)24(17-38-5)22-6-8-23(9-7-22)28(29,30)31)27(4)10-12-34(13-11-27)26(37)25-20(2)32-18-33-21(25)3/h6-9,18-19,24H,10-17H2,1-5H3/t19-,24-/m0/s1
IUPAC Name
5-{4-[(3S)-4-[(1R)-2-methoxy-1-[4-(trifluoromethyl)phenyl]ethyl]-3-methylpiperazin-1-yl]-4-methylpiperidine-1-carbonyl}-4,6-dimethylpyrimidine
SMILES
COC[C@H](N1CCN(C[C@@H]1C)C1(C)CCN(CC1)C(=O)C1=C(C)N=CN=C1C)C1=CC=C(C=C1)C(F)(F)F

Pharmacology

Indication

Investigated for use/treatment in HIV infection and viral infection.

Pharmacodynamics
Not Available
Mechanism of action

Vicriviroc is a noncompetitive allosteric antagonist of CCR5. It is orally administered and, because it is effective at nanomolar concentrations, it can be administered once daily. Vicriviroc binds to a small hydrophobic pocket between the transmembrane helices near the extracellular surface of the CCR5 receptor. Binding to this pocket induces a conformational change of the extracellular segment of CCR5 and prevents binding of gp120 to the target cell, consequently preventing the virus from entering the target cell at all.

TargetActionsOrganism
UC-C chemokine receptor type 5Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Metabolised primarily by the CYP3A4 system

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
DrugInteraction
AbirateroneThe metabolism of Vicriviroc can be decreased when combined with Abiraterone.
AcetazolamideThe metabolism of Vicriviroc can be decreased when combined with Acetazolamide.
Acetyl sulfisoxazoleThe metabolism of Vicriviroc can be decreased when combined with Acetyl sulfisoxazole.
AlbendazoleThe metabolism of Vicriviroc can be decreased when combined with Albendazole.
AlclometasoneThe metabolism of Alclometasone can be decreased when combined with Vicriviroc.
AlfentanilThe metabolism of Alfentanil can be decreased when combined with Vicriviroc.
AlfuzosinThe metabolism of Vicriviroc can be decreased when combined with Alfuzosin.
AlmotriptanThe metabolism of Vicriviroc can be decreased when combined with Almotriptan.
AlosetronThe metabolism of Vicriviroc can be decreased when combined with Alosetron.
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Vicriviroc.
Food Interactions
Not Available

References

General References
  1. Idemyor V: Human immunodeficiency virus (HIV) entry inhibitors (CCR5 specific blockers) in development: are they the next novel therapies? HIV Clin Trials. 2005 Sep-Oct;6(5):272-7. [PubMed:16306033]
  2. Emmelkamp JM, Rockstroh JK: CCR5 antagonists: comparison of efficacy, side effects, pharmacokinetics and interactions--review of the literature. Eur J Med Res. 2007 Oct 15;12(9):409-17. [PubMed:17933722]
  3. Ghosal A, Ramanathan R, Yuan Y, Hapangama N, Chowdhury SK, Kishnani NS, Alton KB: Identification of human liver cytochrome P450 enzymes involved in biotransformation of vicriviroc, a CCR5 receptor antagonist. Drug Metab Dispos. 2007 Dec;35(12):2186-95. Epub 2007 Sep 7. [PubMed:17827338]
External Links
ChemSpider
2278662
BindingDB
50145685
ChEBI
94843
ChEMBL
CHEMBL82301
Wikipedia
Vicriviroc

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
1, 2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections4
2RecruitingTreatmentNeoplasms, Colorectal1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections2
3TerminatedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1

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 Solubility0.0362 mg/mLALOGPS
logP3.29ALOGPS
logP2.8ChemAxon
logS-4.2ALOGPS
pKa (Strongest Basic)8.85ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area61.8 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity142.64 m3·mol-1ChemAxon
Polarizability56.3 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

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 trifluoromethylbenzenes. These are organofluorine compounds that contain a benzene ring substituted with one or more trifluoromethyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Trifluoromethylbenzenes
Direct Parent
Trifluoromethylbenzenes
Alternative Parents
Pyrimidinecarboxylic acids and derivatives / N-acylpiperidines / Aminopiperidines / Aralkylamines / N-alkylpiperazines / Tertiary carboxylic acid amides / Heteroaromatic compounds / Trialkylamines / Amino acids and derivatives / Azacyclic compounds
show 6 more
Substituents
Trifluoromethylbenzene / N-acyl-piperidine / Pyrimidine-5-carboxylic acid or derivatives / 4-aminopiperidine / N-alkylpiperazine / Aralkylamine / 1,4-diazinane / Piperazine / Piperidine / Pyrimidine
show 24 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Virus receptor activity
Specific Function
Receptor for a number of inflammatory CC-chemokines including MIP-1-alpha, MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a r...
Gene Name
CCR5
Uniprot ID
P51681
Uniprot Name
C-C chemokine receptor type 5
Molecular Weight
40523.645 Da
References
  1. Wilkin TJ, Su Z, Kuritzkes DR, Hughes M, Flexner C, Gross R, Coakley E, Greaves W, Godfrey C, Skolnik PR, Timpone J, Rodriguez B, Gulick RM: HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor: AIDS Clinical Trial Group A5211. Clin Infect Dis. 2007 Feb 15;44(4):591-5. Epub 2007 Jan 17. [PubMed:17243065]
  2. Tsibris AM, Sagar M, Gulick RM, Su Z, Hughes M, Greaves W, Subramanian M, Flexner C, Giguel F, Leopold KE, Coakley E, Kuritzkes DR: In vivo emergence of vicriviroc resistance in a human immunodeficiency virus type 1 subtype C-infected subject. J Virol. 2008 Aug;82(16):8210-4. doi: 10.1128/JVI.00444-08. Epub 2008 May 21. [PubMed:18495779]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]

Drug created on March 19, 2008 10:44 / Updated on October 01, 2018 16:46