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Details

Stereochemistry ABSOLUTE
Molecular Formula C28H38F3N5O2
Molecular Weight 533.6299
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VICRIVIROC

SMILES

C[C@@]1([H])CN(CCN1[C@@]([H])(COC)c2ccc(cc2)C(F)(F)F)C3(C)CCN(CC3)C(=O)c4c(C)ncnc4C

InChI

InChIKey=CNPVJJQCETWNEU-CYFREDJKSA-N
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

HIDE SMILES / InChI

Molecular Formula C28H38F3N5O2
Molecular Weight 533.6299
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16304152 | https://aidsinfo.nih.gov/drugs/519/vicriviroc/0/patient

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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
63 ng/mL
5 mg 1 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VICRIVIROC plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
131 ng/mL
10 mg 1 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VICRIVIROC plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
181 ng/mL
15 mg 1 times / day steady-state, oral
dose: 15 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VICRIVIROC plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
149 ng/mL
20.5 mg 2 times / day steady-state, oral
dose: 20.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VICRIVIROC plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
342 ng/mL
41.1 mg 2 times / day steady-state, oral
dose: 41.1 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VICRIVIROC plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
65 ng/mL
8.2 mg 2 times / day steady-state, oral
dose: 8.2 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VICRIVIROC plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1172 ng × h/mL
5 mg 1 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VICRIVIROC plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2502 ng × h/mL
10 mg 1 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VICRIVIROC plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3390 ng × h/mL
15 mg 1 times / day steady-state, oral
dose: 15 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VICRIVIROC plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1060 ng × h/mL
20.5 mg 2 times / day steady-state, oral
dose: 20.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VICRIVIROC plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2290 ng × h/mL
41.1 mg 2 times / day steady-state, oral
dose: 41.1 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VICRIVIROC plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
424 ng × h/mL
8.2 mg 2 times / day steady-state, oral
dose: 8.2 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VICRIVIROC plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
29 h
20.5 mg 2 times / day steady-state, oral
dose: 20.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VICRIVIROC plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
28 h
41.1 mg 2 times / day steady-state, oral
dose: 41.1 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VICRIVIROC plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
33 h
8.2 mg 2 times / day steady-state, oral
dose: 8.2 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VICRIVIROC plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
V3 loop truncations in HIV-1 envelope impart resistance to coreceptor inhibitors and enhanced sensitivity to neutralizing antibodies.
2007 Aug 24
Identification of human liver cytochrome P450 enzymes involved in biotransformation of vicriviroc, a CCR5 receptor antagonist.
2007 Dec
Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-Infected, treatment-experienced patients: AIDS clinical trials group 5211.
2007 Jul 15
Escape of HIV-1 from a small molecule CCR5 inhibitor is not associated with a fitness loss.
2007 Jun
Antiviral activity, pharmacokinetics and safety of vicriviroc, an oral CCR5 antagonist, during 14-day monotherapy in HIV-infected adults.
2007 Jun 19
Access denied? The status of co-receptor inhibition to counter HIV entry.
2007 May
Antiviral drugs in the treatment of AIDS: what is in the pipeline ?
2007 Oct 15
CCR5 antagonists in the treatment of treatment-naive patients infected with CCR5 tropic HIV-1.
2007 Oct 15
CCR5 antagonists in the treatment of treatment-experienced patients infected with CCR5 tropic HIV-1.
2007 Oct 15
CCR5 antagonists: comparison of efficacy, side effects, pharmacokinetics and interactions--review of the literature.
2007 Oct 15
HIV-1 drug-resistance and drug-dependence.
2007 Oct 25
Mapping resistance to the CCR5 co-receptor antagonist vicriviroc using heterologous chimeric HIV-1 envelope genes reveals key determinants in the C2-V5 domain of gp120.
2008 Apr 10
Neutralizing antibody and anti-retroviral drug sensitivities of HIV-1 isolates resistant to small molecule CCR5 inhibitors.
2008 Aug 1
Long-term safety study of vicriviroc presented.
2008 Dec
Better results from vicriviroc with new Trofile test.
2008 Dec
Topical application of entry inhibitors as "virustats" to prevent sexual transmission of HIV infection.
2008 Dec 18
[CCR5 antagonists: a new class of antiretrovirals].
2008 Mar
Molecular interactions of CCR5 with major classes of small-molecule anti-HIV CCR5 antagonists.
2008 Mar
Distinct efficacy of HIV-1 entry inhibitors to prevent cell-to-cell transfer of R5 and X4 viruses across a human placental trophoblast barrier in a reconstitution model in vitro.
2008 Mar 31
Phase II study of vicriviroc versus efavirenz (both with zidovudine/lamivudine) in treatment-naive subjects with HIV-1 infection.
2008 Oct 15
[Chemokine receptors and its importance in the replication cycle of human immunodeficiency virus: clinical and therapeutic implications].
2008 Sep-Oct
Pharmacologic and nonpharmacologic options for the management of HIV infection during pregnancy.
2009
Novel compounds for the treatment of HIV type-1 infection.
2009
The chemokine system and CCR5 antagonists: potential in HIV treatment and other novel therapies.
2009 Apr
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
HIV entry: new insights and implications for patient management.
2009 Feb
Gateways to clinical trials.
2009 Jul-Aug
Pharmacotherapy of pediatric and adolescent HIV infection.
2009 Jun
Inefficient entry of vicriviroc-resistant HIV-1 via the inhibitor-CCR5 complex at low cell surface CCR5 densities.
2009 May 10
Novel drug classes: entry inhibitors [enfuvirtide, chemokine (C-C motif) receptor 5 antagonists].
2009 Nov
Long-term data on vicriviroc released.
2009 Nov
Efavirenz: a decade of clinical experience in the treatment of HIV.
2009 Nov
Gateways to clinical trials.
2009 Sep
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
Potential use of rapamycin in HIV infection.
2010 Dec
Evolution of CCR5 antagonist resistance in an HIV-1 subtype C clinical isolate.
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
Vicriviroc and peripheral neuropathy: results from AIDS Clinical Trials Group 5211.
2010 Jan-Feb
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
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
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

One tablet of vicriviroc 30 mg once daily.
Route of Administration: Oral
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 Sat Jun 26 14:52:42 UTC 2021
Edited
by admin
on Sat Jun 26 14:52:42 UTC 2021
Record UNII
TL515DW4QS
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VICRIVIROC
INN   MI   WHO-DD  
INN  
Official Name English
VICRIVIROC [WHO-DD]
Common Name English
MK-4176
Code English
SCH-417690 FREE BASE
Code English
SCH-D
Code English
MK-7690
Code English
VICRIVIROC [MI]
Common Name English
5-((4-((3S)-4-((1R)-2-METHOXY-1-(4-(TRIFLUOROMETHYL)PHENYL)ETHYL)-3-METHYLPIPERAZIN-1-YL)-4-METHYLPIPERIDIN-1-YL)CARBONYL)-4,6-DIMETHYLPYRIMIDINE
Systematic Name English
VICRIVIROC [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C63817
Created by admin on Sat Jun 26 14:52:43 UTC 2021 , Edited by admin on Sat Jun 26 14:52:43 UTC 2021
NCI_THESAURUS C1660
Created by admin on Sat Jun 26 14:52:43 UTC 2021 , Edited by admin on Sat Jun 26 14:52:43 UTC 2021
Code System Code Type Description
WIKIPEDIA
VICRIVIROC
Created by admin on Sat Jun 26 14:52:43 UTC 2021 , Edited by admin on Sat Jun 26 14:52:43 UTC 2021
PRIMARY
MERCK INDEX
M11442
Created by admin on Sat Jun 26 14:52:43 UTC 2021 , Edited by admin on Sat Jun 26 14:52:43 UTC 2021
PRIMARY Merck Index
FDA UNII
TL515DW4QS
Created by admin on Sat Jun 26 14:52:43 UTC 2021 , Edited by admin on Sat Jun 26 14:52:43 UTC 2021
PRIMARY
EVMPD
SUB77762
Created by admin on Sat Jun 26 14:52:43 UTC 2021 , Edited by admin on Sat Jun 26 14:52:43 UTC 2021
PRIMARY
MESH
C486781
Created by admin on Sat Jun 26 14:52:43 UTC 2021 , Edited by admin on Sat Jun 26 14:52:43 UTC 2021
PRIMARY
PUBCHEM
3009355
Created by admin on Sat Jun 26 14:52:43 UTC 2021 , Edited by admin on Sat Jun 26 14:52:43 UTC 2021
PRIMARY
DRUG BANK
DB06652
Created by admin on Sat Jun 26 14:52:43 UTC 2021 , Edited by admin on Sat Jun 26 14:52:43 UTC 2021
PRIMARY
INN
8647
Created by admin on Sat Jun 26 14:52:43 UTC 2021 , Edited by admin on Sat Jun 26 14:52:43 UTC 2021
PRIMARY
NCI_THESAURUS
C73589
Created by admin on Sat Jun 26 14:52:43 UTC 2021 , Edited by admin on Sat Jun 26 14:52:43 UTC 2021
PRIMARY
CAS
306296-47-9
Created by admin on Sat Jun 26 14:52:43 UTC 2021 , Edited by admin on Sat Jun 26 14:52:43 UTC 2021
PRIMARY
ChEMBL
CHEMBL82301
Created by admin on Sat Jun 26 14:52:43 UTC 2021 , Edited by admin on Sat Jun 26 14:52:43 UTC 2021
PRIMARY
Related Record Type Details
TARGET ORGANISM->INHIBITOR
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY