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Details

Stereochemistry ACHIRAL
Molecular Formula C20H19N5
Molecular Weight 329.3991
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DAPIVIRINE

SMILES

Cc1cc(C)c(c(C)c1)N=c2ccnc(Nc3ccc(cc3)C#N)[nH]2

InChI

InChIKey=ILAYIAGXTHKHNT-UHFFFAOYSA-N
InChI=1S/C20H19N5/c1-13-10-14(2)19(15(3)11-13)24-18-8-9-22-20(25-18)23-17-6-4-16(12-21)5-7-17/h4-11H,1-3H3,(H2,22,23,24,25)

HIDE SMILES / InChI

Molecular Formula C20H19N5
Molecular Weight 329.3991
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created using several sources including: http://www.mtnstopshiv.org/news/studies/mtn020 | https://www.ncbi.nlm.nih.gov/pubmed/14693562 | https://clinicaltrials.gov/ct2/show/NCT02010593

Dapivirine, an anti-retroviral (ARV)-based microbicide, is a substituted diaminopyrimidine (DAPY) derivative and a potent non-nucleoside reverse-transcriptase inhibitor (NNRTI) with antiviral activity against HIV-1. Dapivirine showed high activity against wild-type and mutant HIV in in virto HIV models inhibiting a broad panel of HIV-1 isolates from different classes, including a wide range of NNRTI-resistant isolates. Developed by Janssen Sciences (formerly Tibotec Pharmaceuticals), dapivirine was initially tested as an oral treatment for HIV in a number of Phase I/II clinical trials. In 2014 the International Partnership for Microbicides (IPM) began its work on the monthly dapivirine ring. Phase I/II clinical trials in Africa, Europe and the United States proved that dapivirine is safe and well-tolerated. Phase III long-term safety and efficacy studies of the monthly dapivirine ring as part of IPM's Dapivirine Ring Licensure Program confirmed that the monthly dapivirine ring can safely help prevent HIV infection in women. In 2016 the ASPIRE Study reported a 27 percent reduction in HIV-1 acquisition with a trend toward greater protection in women over age 21 and no significant protection for women under age 21.

Originator

Curator's Comment:: In 2004, Tibotec granted International Partnership for Microbicides (IPM) a non-exclusive, royalty-free license to develop dapivirine as a microbicide for use in resource-poor countries. This agreement expanded in 2014, when Janssen granted IPM exclusive worldwide rights to dapivirine.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Correlations between factors determining the pharmacokinetics and antiviral activity of HIV-1 non-nucleoside reverse transcriptase inhibitors of the diaryltriazine and diarylpyrimidine classes of compounds.
2004
TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1.
2004 Dec
In search of a novel anti-HIV drug: multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2- pyrimidinyl]amino]benzonitrile (R278474, rilpivirine).
2005 Mar 24
Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol.
2006 Nov
Inhibition of human immunodeficiency virus type 1 infection by the candidate microbicide dapivirine, a nonnucleoside reverse transcriptase inhibitor.
2009 Feb
Selective killing of human immunodeficiency virus infected cells by non-nucleoside reverse transcriptase inhibitor-induced activation of HIV protease.
2010 Oct 15
Inhibition of HIV-1 by non-nucleoside reverse transcriptase inhibitors via an induced fit mechanism-Importance of slow dissociation and relaxation rates for antiviral efficacy.
2010 Oct 15
Complete inactivation of HIV-1 using photo-labeled non-nucleoside reverse transcriptase inhibitors.
2011 Jan
Synthesis, evaluation and structure-activity relationships of triazine dimers as novel antiviral agents.
2012 Dec 1
Optimization of diarylazines as anti-HIV agents with dramatically enhanced solubility.
2013 Sep 15
Patents

Sample Use Guides

The dapivirine matrix vaginal ring containing 25 mg of drug substance dispersed in a platinum-catalyzed-cured silicone matrix inserts once every 4 weeks in postmenopausal women over 12 weeks of product use.
Route of Administration: Other
A 24-h treatment with 100 nM TMC120-R147681 (dapivirine) prevented cell-free HIV infection, whereas 10-fold-higher concentrations blocked cell-associated HIV when studied using monocyte-derived dendritic cells (MO-DC) and autologous CD4+ T cells, representing early targets during sexual transmission.
Substance Class Chemical
Created
by admin
on Sat Jun 26 11:06:16 UTC 2021
Edited
by admin
on Sat Jun 26 11:06:16 UTC 2021
Record UNII
TCN4MG2VXS
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DAPIVIRINE
INN   USAN  
INN   USAN  
Official Name English
4-((4-((2,4,6-TRIMETHYLPHENYL)AMINO)PYRIMIDIN-2-YL)AMINO)BENZONITRILE
Systematic Name English
DAPIVIRINE [USAN]
Common Name English
AIDS-105293
Code English
R-147681
Code English
DAPIVIRINE [WHO-DD]
Common Name English
GEL-02
Common Name English
DAPIVIRINE [INN]
Common Name English
TMC-120
Code English
Classification Tree Code System Code
WHO-ATC G01AX17
Created by admin on Sat Jun 26 11:06:17 UTC 2021 , Edited by admin on Sat Jun 26 11:06:17 UTC 2021
NCI_THESAURUS C97453
Created by admin on Sat Jun 26 11:06:17 UTC 2021 , Edited by admin on Sat Jun 26 11:06:17 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL70663
Created by admin on Sat Jun 26 11:06:17 UTC 2021 , Edited by admin on Sat Jun 26 11:06:17 UTC 2021
PRIMARY
DRUG BANK
DB08639
Created by admin on Sat Jun 26 11:06:17 UTC 2021 , Edited by admin on Sat Jun 26 11:06:17 UTC 2021
PRIMARY
NCI_THESAURUS
C73205
Created by admin on Sat Jun 26 11:06:17 UTC 2021 , Edited by admin on Sat Jun 26 11:06:17 UTC 2021
PRIMARY
PUBCHEM
214347
Created by admin on Sat Jun 26 11:06:17 UTC 2021 , Edited by admin on Sat Jun 26 11:06:17 UTC 2021
PRIMARY
EPA CompTox
244767-67-7
Created by admin on Sat Jun 26 11:06:17 UTC 2021 , Edited by admin on Sat Jun 26 11:06:17 UTC 2021
PRIMARY
INN
8164
Created by admin on Sat Jun 26 11:06:17 UTC 2021 , Edited by admin on Sat Jun 26 11:06:17 UTC 2021
PRIMARY
CAS
244767-67-7
Created by admin on Sat Jun 26 11:06:17 UTC 2021 , Edited by admin on Sat Jun 26 11:06:17 UTC 2021
PRIMARY
FDA UNII
TCN4MG2VXS
Created by admin on Sat Jun 26 11:06:17 UTC 2021 , Edited by admin on Sat Jun 26 11:06:17 UTC 2021
PRIMARY
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TARGET ORGANISM->INHIBITOR
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