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Details

Stereochemistry ABSOLUTE
Molecular Formula C28H38F3N5O2.C4H4O4
Molecular Weight 649.701
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of VICRIVIROC MALEATE

SMILES

OC(=O)\C=C/C(O)=O.COC[C@H](N1CCN(C[C@@H]1C)C2(C)CCN(CC2)C(=O)C3=C(C)N=CN=C3C)C4=CC=C(C=C4)C(F)(F)F

InChI

InChIKey=GXINKQQWHLIBJA-UCIBKFKQSA-N
InChI=1S/C28H38F3N5O2.C4H4O4/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;5-3(6)1-2-4(7)8/h6-9,18-19,24H,10-17H2,1-5H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t19-,24-;/m0./s1

HIDE SMILES / InChI

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Molecular Formula C28H38F3N5O2
Molecular Weight 533.6288
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Vicriviroc or SCH 417690 is a potent and selective antagonist of the CCR5 receptor. vicriviroc binds specifically to the CCR5 receptor and prevents infection of target cells by CCR5-tropic HIV-1 isolates. In antiviral assays, vicriviroc showed potent, broad-spectrum activity against genetically diverse and drug-resistant HIV-1 isolates and was consistently more active than SCH-C in inhibiting viral replication. This compound demonstrated synergistic anti-HIV activity in combination with drugs from all other classes of approved antiretrovirals. Competition binding assays revealed that vicriviroc binds with higher affinity to CCR5 than SCH-C. Functional assays, including inhibition of calcium flux, guanosine 5'-[35S]triphosphate exchange, and chemotaxis, confirmed that vicriviroc acts as a receptor antagonist by inhibiting signaling of CCR5 by chemokines. Finally, vicriviroc demonstrated diminished affinity for the human ether a-go-go related gene transcript ion channel compared to SCH-C, suggesting a reduced potential for cardiac effects. Vicriviroc represented a promising new candidate for the treatment of HIV-1 infection. Vicriviroc for HIV treatment was previously in Phase III studies but has since been discontinued.

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
New targets in antiretroviral therapy 2006.
2006 Sep
Maraviroc: the evidence for its potential in the management of HIV.
2007 Mar 31
Pharmacologic characteristics of investigational and recently approved agents for the treatment of HIV.
2008 May
Pharmacologic and nonpharmacologic options for the management of HIV infection during pregnancy.
2009
Drug interactions with new and investigational antiretrovirals.
2009
Novel compounds for the treatment of HIV type-1 infection.
2009
Two HIV-1 variants resistant to small molecule CCR5 inhibitors differ in how they use CCR5 for entry.
2009 Aug
Vicriviroc, a CCR5 receptor antagonist for the potential treatment of HIV infection.
2009 Aug
Antiretroviral therapy: new drugs, formulations, ideas, and strategies.
2009 Dec
Response to vicriviroc in treatment-experienced subjects, as determined by an enhanced-sensitivity coreceptor tropism assay: reanalysis of AIDS clinical trials group A5211.
2009 Dec 1
HIV entry: new insights and implications for patient management.
2009 Feb
Maraviroc in the treatment of HIV infection.
2009 Feb 6
CCR5 inhibitors: Emerging promising HIV therapeutic strategy.
2009 Jan
Gateways to clinical trials.
2009 Jul-Aug
Pharmacotherapy of pediatric and adolescent HIV infection.
2009 Jun
Novel drug classes: entry inhibitors [enfuvirtide, chemokine (C-C motif) receptor 5 antagonists].
2009 Nov
Long-term data on vicriviroc released.
2009 Nov
Vicriviroc: a CCR5 antagonist for treatment-experienced patients with HIV-1 infection.
2009 Nov
Efavirenz: a decade of clinical experience in the treatment of HIV.
2009 Nov
Gateways to clinical trials.
2009 Sep
Profile of maraviroc: a CCR5 antagonist in the management of treatment-experienced HIV patients.
2010
Pharmacokinetic/pharmacodynamic modeling of the antiretroviral activity of the CCR5 antagonist Vicriviroc in treatment experienced HIV-infected subjects (ACTG protocol 5211).
2010 Apr
Clinical resistance to vicriviroc through adaptive V3 loop mutations in HIV-1 subtype D gp120 that alter interactions with the N-terminus and ECL2 of CCR5.
2010 Apr 25
Three-year safety and efficacy of vicriviroc, a CCR5 antagonist, in HIV-1-infected treatment-experienced patients.
2010 Aug
Gateways to clinical trials.
2010 Dec
Potential use of rapamycin in HIV infection.
2010 Dec
Evolution of CCR5 antagonist resistance in an HIV-1 subtype C clinical isolate.
2010 Dec
C-C chemokine receptor type 5 (CCR5) utilization of transmitted and early founder human immunodeficiency virus type 1 envelopes and sensitivity to small-molecule CCR5 inhibitors.
2010 Dec
Early development of non-hodgkin lymphoma following initiation of newer class antiretroviral therapy among HIV-infected patients - implications for immune reconstitution.
2010 Dec 14
CCR5: From Natural Resistance to a New Anti-HIV Strategy.
2010 Feb
Vicriviroc in combination therapy with an optimized regimen for treatment-experienced subjects: 48-week results of the VICTOR-E1 phase 2 trial.
2010 Feb 15
Short-term administration of the CCR5 antagonist vicriviroc to patients with HIV and HCV coinfection is safe and tolerable.
2010 Jan
Pharmacokinetics and drug-drug interactions of antiretrovirals: an update.
2010 Jan
Vicriviroc and peripheral neuropathy: results from AIDS Clinical Trials Group 5211.
2010 Jan-Feb
Short communication: antiretroviral therapy resistance mutations present in the HIV type 1 subtype C pol and env regions from therapy-naive patients in Zambia.
2010 Jul
Gateways to clinical trials.
2010 Jun
Renal insufficiency has no effect on the pharmacokinetics of vicriviroc in a ritonavir-containing regimen.
2010 Jun
Disappointing results for vicriviroc.
2010 Mar
HIV-1 Entry, Inhibitors, and Resistance.
2010 May
Characterization of emergent HIV resistance in treatment-naive subjects enrolled in a vicriviroc phase 2 trial.
2010 May 15
Therapeutic immunization with HIV-1 Tat reduces immune activation and loss of regulatory T-cells and improves immune function in subjects on HAART.
2010 Nov 11
Structure of HIV-1 quasi-species as early indicator for switches of co-receptor tropism.
2010 Nov 30
A maraviroc-resistant HIV-1 with narrow cross-resistance to other CCR5 antagonists depends on both N-terminal and extracellular loop domains of drug-bound CCR5.
2010 Oct
GenHtr: a tool for comparative assessment of genetic heterogeneity in microbial genomes generated by massive short-read sequencing.
2010 Oct 12
Vicriviroc, a new CC-chemokine receptor 5 inhibitor for treatment of HIV: properties, promises and challenges.
2010 Sep
Identification and characterization of INCB9471, an allosteric noncompetitive small-molecule antagonist of C-C chemokine receptor 5 with potent inhibitory activity against monocyte migration and HIV-1 infection.
2011 Jul
Novel 4,4-disubstituted piperidine-based C-C chemokine receptor-5 inhibitors with high potency against human immunodeficiency virus-1 and an improved human ether-a-go-go related gene (hERG) profile.
2011 Jun 9
Conjugation of cell-penetrating peptides leads to identification of anti-HIV peptides from matrix proteins.
2012 Feb 15
Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance.
2012 Jul 5
Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance.
2013 Jun 7
Patents

Patents

Sample Use Guides

In Vivo Use Guide
One tablet of vicriviroc 30 mg once daily.
Route of Administration: Oral
In Vitro Use Guide
Vicriviroc potently inhibited all the HIV-1 isolates in PBMCs isolates tested, with geometric mean EC50s ranging between 0.04 nM and 2.3 nM and IC90s between 0.45 nM and 18 nM
Substance Class Chemical
Created
by admin
on Tue Oct 22 01:36:17 UTC 2019
Edited
by admin
on Tue Oct 22 01:36:17 UTC 2019
Record UNII
EP3QG127N9
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VICRIVIROC MALEATE
MI   USAN  
USAN  
Official Name English
SCH 417690
Code English
SCH-417690
Code English
VICRIVIROC MALEATE [MI]
Common Name English
VICRIVIROC MALEATE [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1660
Created by admin on Tue Oct 22 01:36:17 UTC 2019 , Edited by admin on Tue Oct 22 01:36:17 UTC 2019
NCI_THESAURUS C63817
Created by admin on Tue Oct 22 01:36:17 UTC 2019 , Edited by admin on Tue Oct 22 01:36:17 UTC 2019
Code System Code Type Description
PUBCHEM
6451165
Created by admin on Tue Oct 22 01:36:17 UTC 2019 , Edited by admin on Tue Oct 22 01:36:17 UTC 2019
PRIMARY
NCI_THESAURUS
C73146
Created by admin on Tue Oct 22 01:36:17 UTC 2019 , Edited by admin on Tue Oct 22 01:36:17 UTC 2019
PRIMARY
ChEMBL
CHEMBL82301
Created by admin on Tue Oct 22 01:36:17 UTC 2019 , Edited by admin on Tue Oct 22 01:36:17 UTC 2019
PRIMARY
EPA CompTox
599179-03-0
Created by admin on Tue Oct 22 01:36:17 UTC 2019 , Edited by admin on Tue Oct 22 01:36:17 UTC 2019
PRIMARY
MERCK INDEX
M11442
Created by admin on Tue Oct 22 01:36:17 UTC 2019 , Edited by admin on Tue Oct 22 01:36:17 UTC 2019
PRIMARY Merck Index
CAS
599179-03-0
Created by admin on Tue Oct 22 01:36:17 UTC 2019 , Edited by admin on Tue Oct 22 01:36:17 UTC 2019
PRIMARY
EVMPD
SUB35087
Created by admin on Tue Oct 22 01:36:17 UTC 2019 , Edited by admin on Tue Oct 22 01:36:17 UTC 2019
PRIMARY
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PARENT -> SALT/SOLVATE
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ACTIVE MOIETY