Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C28H38F3N5O2 |
| Molecular Weight | 533.6288 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
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=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
| Molecular Formula | C28H38F3N5O2 |
| Molecular Weight | 533.6288 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionCurator'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
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
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
63 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20071999 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20071999 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20071999 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1172 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20071999 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20071999 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20071999 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
29 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705 |
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 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| CCR5 antagonists: host-targeted antivirals for the treatment of HIV infection. | 2005 |
|
| Report from the 13th retrovirus conference. Vicriviroc less effective than efavirenz in treatment-naive patients. | 2006 Apr |
|
| Anti-HIV agents. Vicriviroc: is the risk of cancer increased? | 2006 Aug-Sep |
|
| Recent advances of CCR5 antagonists. | 2006 Sep |
|
| V3 loop truncations in HIV-1 envelope impart resistance to coreceptor inhibitors and enhanced sensitivity to neutralizing antibodies. | 2007 Aug 24 |
|
| 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 |
|
| Maraviroc: the evidence for its potential in the management of HIV. | 2007 Mar 31 |
|
| CCR5 antagonists in the treatment of treatment-naive 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 |
|
| New approaches in the treatment of HIV/AIDS - focus on maraviroc and other CCR5 antagonists. | 2008 Apr |
|
| 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 |
|
| [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 |
|
| Novel targets for antiretroviral therapy: clinical progress to date. | 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 |
|
| 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 |
|
| HIV-1 entry inhibitors: an overview. | 2009 Mar |
|
| The relative activity of "function sparing" HIV-1 entry inhibitors on viral entry and CCR5 internalization: is allosteric functional selectivity a valuable therapeutic property? | 2009 Mar |
|
| 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 |
|
| Profile of maraviroc: a CCR5 antagonist in the management of treatment-experienced HIV patients. | 2010 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| 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
Sample Use Guides
| Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 16:04:15 GMT 2023
by
admin
on
Fri Dec 15 16:04:15 GMT 2023
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| Record UNII |
TL515DW4QS
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Validated (UNII)
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NCI_THESAURUS |
C63817
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NCI_THESAURUS |
C1660
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VICRIVIROC
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m11442
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TL515DW4QS
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DTXSID40897719
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SUB77762
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C486781
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3009355
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100000138309
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DB06652
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8647
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C73589
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306296-47-9
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CHEMBL82301
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TARGET ORGANISM->INHIBITOR |
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SALT/SOLVATE -> PARENT |
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ACTIVE MOIETY |
