4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethyl-phenyl]amino]pyrimidin-2-yl]amino]benzonitrile Property

Melting point:

245℃

Boiling point:

634.1±65.0 °C(Predicted)

Density 

1.27

storage temp. 

Refrigerator

solubility 

Acetone (Slightly), Chloroform (Slightly), DMSO (Slightly), Water (Very Slightly)

pka

4.56±0.10(Predicted)

form 

Solid

color 

Yellow

Safety

Hazardous Substances Data

500287-72-9(Hazardous Substances Data)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H319Causes serious eye irritation

H400Very toxic to aquatic life

H410Very toxic to aquatic life with long lasting effects

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P273Avoid release to the environment.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P330Rinse mouth.

P391Collect spillage. Hazardous to the aquatic environment

P501Dispose of contents/container to..…

4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethyl-phenyl]amino]pyrimidin-2-yl]amino]benzonitrile Chemical Properties,Usage,Production

Description

In May 2011, the U.S. FDA approved rilpivirine in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV) 1 infection in treatment-naive adult patients. Rilpivirine is a member of the nonnucleoside reverse transcriptase inhibitor (NNRTI) class of anti-HIV agents. It is highly potent against a range of wild-type HIV strains (EC50=0.07–1.0 nM),～10–20 timesmore potent than the NNRTI efavirenz (Sustiva), and active against HIV strains resistant to other NNRTIs. The discovery of rilpivirine was guided by molecular modeling and X-ray crystallography of HIV-1 RT complexed with inhibitors. The synthesis of rilpivirine is accomplished by an efficient 6-step route in which the key step is coupling of 4-((4-chloropyrimidin-2-yl)amino)benzonitrile with (E)-3-(4-amino-3,5-dimethylphenyl)acrylonitrile.

Chemical Properties

N/ABright Yellow Solid

Originator

Janssen (Belgium)

Uses

A novel non-nucleoside reverse transcriptase inhibitor. Rilpivirine seems to be well tolerated with less CNS disturbance than Efavirenz, and has non-teratogenic potential. An anti-HIV agent.

Definition

ChEBI: An aminopyrimidine that is pyrimidine-2,4-diamine in which the amino groups at positions 2 and 4 are substituted by 4-cyanophenyl and 4-[(E)-2-cyanovinyl]-2,6-dimethylphenyl groups respectively. Used for treatment of HIV.

brand name

Edurant

Clinical Use

Non-nucleoside reverse transcriptase inhibitor:
Treatment of progressive or advanced HIV infection in combination with at least two other antivirals

target

reverse transcriptase

Drug interactions

Potentially hazardous interactions with other drugs
Antibacterials: avoid with clarithromycin and erythromycin - concentration possibly increased; concentration decreased by rifampicin and rifabutin - avoid with rifampicin, increase dose of rilpivirine to 50 mg daily.
Antidepressants: concentration possibly reduced by St John’s wort - avoid.
Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin, oxcarbazepine, phenobarbital, primidone and phenytoin - avoid.
Corticosteroids: avoid with dexamethasone (except as a single dose).
Orlistat: absorption possibly reduced by orlistat.
Ulcer-healing drugs: concentration possibly reduced by esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole - avoid; avoid histamine H2 -antagonists for 12 hours before and 4 hours after rilpiverine.

Metabolism

Primarily undergoes oxidative metabolism mediated by the cytochrome P450 (CYP) 3A system.
85% excreted via the faeces (25% as unchanged drug) and 6% via the urine.

storage

Store at -20°C

References

[1] moss d m, liptrott n j, curley p, et al. rilpivirine inhibits drug transporters abcb1, slc22a1, and slc22a2 in vitro. antimicrobial agents and chemotherapy, 2013, 57(11): 5612-5618.
[2] garvey l, winston a. rilpivirine: a novel non-nucleoside reverse transcriptase inhibitor. 2009.
[3] weiss j, haefeli w e. potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. international journal of antimicrobial agents, 2013, 41(5): 484-487.
[4] baert l, van’t klooster g, dries w, et al. development of a long-acting injectable formulation with nanoparticles of rilpivirine (tmc278) for hiv treatment. european journal of pharmaceutics and biopharmaceutics, 2009, 72(3): 502-508.