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Details

Stereochemistry ACHIRAL
Molecular Formula C22H18N6
Molecular Weight 366.4193
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of RILPIVIRINE

SMILES

Cc1cc(/C(/[H])=C(\[H])/C#N)cc(C)c1N=c2ccnc(Nc3ccc(cc3)C#N)[nH]2

InChI

InChIKey=YIBOMRUWOWDFLG-ONEGZZNKSA-N
InChI=1S/C22H18N6/c1-15-12-18(4-3-10-23)13-16(2)21(15)27-20-9-11-25-22(28-20)26-19-7-5-17(14-24)6-8-19/h3-9,11-13H,1-2H3,(H2,25,26,27,28)/b4-3+

HIDE SMILES / InChI

Molecular Formula C22H18N6
Molecular Weight 366.4193
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
Curator's Comment:: https://www.ncbi.nlm.nih.gov/pubmed/?term=19933797

Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) which is used for the treatment of HIV-1 infections in treatment-naive patients. It is active against wild-type and NNRTI-resistant HIV-1. Rilpivirine is a diarylpyrimidinethat inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase (RT). Rilpivirine does not inhibit the human cellular DNA polymerases α, β and γ.

CNS Activity

Curator's Comment:: Common side effects may include Central Nervous System (CNS) related side effects including dizziness, difficulty with concentration, sleep disturbances, vivid dreams, agitation, nausea (upset stomach, feeling sick to the stomach), dizziness, sleep disturbances.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Reverse transcriptase/RNaseH (UniProtKB: Q72547)
14 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
EDURANT

Approved Use

In combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-naïve patients with HIV-1 RNA less than or equal to 100,000 copies/mL at the start of therapy.

Launch Date

1305849600000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.14 μg/mL
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RILPIVIRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: FED
121 ng/mL
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RILPIVIRINE plasma
Homo sapiens
population: PREGNANT
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2.38 μg × h/mL
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RILPIVIRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: FED
1792 ng × h/mL
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RILPIVIRINE plasma
Homo sapiens
population: PREGNANT
age: ADULT
sex: FEMALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.3%
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RILPIVIRINE plasma
Homo sapiens
population: PREGNANT
age: ADULT
sex: FEMALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
150 mg 1 times / day multiple, oral
Highest studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 21–66
Health Status: unhealthy
Age Group: 21–66
Sex: M+F
Sources:
Disc. AE: Alanine aminotransferase increase, Aspartate aminotransferase increased...
AEs leading to
discontinuation/dose reduction:
Alanine aminotransferase increase
Aspartate aminotransferase increased
Sources:
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Rash...
AEs leading to
discontinuation/dose reduction:
Rash (0.1%)
Sources:
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Depressive disorders, Suicide attempt...
AEs leading to
discontinuation/dose reduction:
Depressive disorders (severe, 1%)
Suicide attempt (0.29%)
Sources:
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Fat redistribution, Immune reconstitution syndrome...
AEs leading to
discontinuation/dose reduction:
Fat redistribution
Immune reconstitution syndrome
Sources:
AEs

AEs

AESignificanceDosePopulation
Alanine aminotransferase increase Disc. AE
150 mg 1 times / day multiple, oral
Highest studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 21–66
Health Status: unhealthy
Age Group: 21–66
Sex: M+F
Sources:
Aspartate aminotransferase increased Disc. AE
150 mg 1 times / day multiple, oral
Highest studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 21–66
Health Status: unhealthy
Age Group: 21–66
Sex: M+F
Sources:
Rash 0.1%
Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy
Suicide attempt 0.29%
Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy
Depressive disorders severe, 1%
Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy
Fat redistribution Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy
Immune reconstitution syndrome Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy
PubMed

PubMed

TitleDatePubMed
A series of diaryltriazines and diarylpyrimidines are highly potent nonnucleoside reverse transcriptase inhibitors with possible applications as microbicides.
2004 Oct
Synthesis of novel diarylpyrimidine analogues and their antiviral activity against human immunodeficiency virus type 1.
2005 Mar 24
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
Next-generation HIV-1 non-nucleoside reverse transcriptase inhibitors.
2006 Feb
Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 wild-type and mutant strains.
2007 May
Rilpivirine: a novel non-nucleoside reverse transcriptase inhibitor.
2009 Jul
TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1.
2010 Feb
Rilpivirine: a next-generation non-nucleoside analogue for the treatment of HIV infection.
2012 May
Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro.
2013 May
Update on rilpivirine: a new potent non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV replication.
2013 May
In vitro and in vivo activities of AIC292, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor.
2013 Nov
Optimization of diarylazines as anti-HIV agents with dramatically enhanced solubility.
2013 Sep 15
Competitive fitness assays indicate that the E138A substitution in HIV-1 reverse transcriptase decreases in vitro susceptibility to emtricitabine.
2014
In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor.
2014
Discovery of MK-1439, an orally bioavailable non-nucleoside reverse transcriptase inhibitor potent against a wide range of resistant mutant HIV viruses.
2014 Feb 1
Patents

Sample Use Guides

25 mg (one 25 mg tablet) taken once daily with a meal, is not recommended for patients less than 12 years of age.
Route of Administration: Oral
TMC278 (rilpivirine) showed subnanomolar 50% effective concentrations (EC50 values) against wild-type HIV-1 group M isolates (0.07 to 1.01 nM) and nanomolar EC50 values against group O isolates (2.88 to 8.45 nM).
Substance Class Chemical
Created
by admin
on Fri Jun 25 23:30:29 UTC 2021
Edited
by admin
on Fri Jun 25 23:30:29 UTC 2021
Record UNII
FI96A8X663
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RILPIVIRINE
DASH   INN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
R278474
Code English
RILPIVIRINE COMPONENT OF CABENUVA
Brand Name English
RILPIVIRINE [INN]
Common Name English
R-278474
Code English
TMC-278
Code English
4-((4-((4-((1E)-2-CYANOETHENYL)-2,6-DIMETHYLPHENYL)AMINO)PYRIMIDIN-2-YL)AMINO)BENZONITRILE
Systematic Name English
RILPIVIRINE [USAN]
Common Name English
RILPIVIRINE [MI]
Common Name English
EDURANT
Brand Name English
RILPIVIRINE [WHO-DD]
Common Name English
BENZONITRILE, 4-((4-((4-((1E)-2-CYANOETHENYL)-2,6-DIMETHYLPHENYL)AMINO)-2- PYRIMIDINYL)AMINO)-
Systematic Name English
CABENUVA COMPONENT RILPIVIRINE
Brand Name English
RILPIVIRINE [VANDF]
Common Name English
RILPIVIRINE [MART.]
Common Name English
TMC278
Code English
RILPIVIRINE [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
WHO-ATC J05AG05
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
WHO-ATC J05AR08
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
NDF-RT N0000175463
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
NCI_THESAURUS C97453
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
WHO-VATC QJ05AG05
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
WHO-ATC J05AR19
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
LIVERTOX 848
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
WHO-ATC J05AR21
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
WHO-VATC QJ05AR08
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C76929
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
PRIMARY
INN
8469
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
PRIMARY
PUBCHEM
6451164
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
PRIMARY
CAS
500287-72-9
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
PRIMARY
DRUG BANK
DB08864
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
PRIMARY
HSDB
8153
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
PRIMARY
MERCK INDEX
M9619
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
PRIMARY Merck Index
EVMPD
SUB31456
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
PRIMARY
RXCUI
1102270
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
PRIMARY RxNorm
EPA CompTox
500287-72-9
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
PRIMARY
WIKIPEDIA
RILPIVIRINE
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
PRIMARY
LACTMED
Rilpivirine
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
PRIMARY
ChEMBL
CHEMBL175691
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
PRIMARY
DRUG CENTRAL
4174
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
PRIMARY
FDA UNII
FI96A8X663
Created by admin on Fri Jun 25 23:30:29 UTC 2021 , Edited by admin on Fri Jun 25 23:30:29 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
FECAL
SALT/SOLVATE -> PARENT
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
MAJOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Blood-to-plasma ratio PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC oral administration