Rilpivirine

Base Information

• Chemical Name: Rilpivirine
• CAS No.: 500287-72-9
• Molecular Formula: C22H18N6
• Molecular Weight: 366.425
• Hs Code.: 2933599090
• European Community (EC) Number: 695-719-5
• UNII: FI96A8X663
• DSSTox Substance ID: DTXSID10198189
• Nikkaji Number: J2.576.528A,J2.980.206H
• Wikipedia: Rilpivirine
• Wikidata: Q421547
• NCI Thesaurus Code: C76929
• RXCUI: 1102270
• Pharos Ligand ID: 3ZHBK2D9PUKP
• Metabolomics Workbench ID: 65119
• ChEMBL ID: CHEMBL175691
• Mol file: 500287-72-9.mol

Synonyms:278, TMC;HCl, Rilpivirine;Hydrochloride, Rilpivirine;R278474;Rilpivirine;Rilpivirine HCl;Rilpivirine Hydrochloride;TMC 278;TMC-278;TMC278

Chemical Property of Rilpivirine

Chemical Property:

• Vapor Pressure: 5.56E-16mmHg at 25°C
• Melting Point: 245 °C
• Refractive Index: 1.665
• Boiling Point: 634.1 °C at 760 mmHg
• PKA: 4.56±0.10(Predicted)
• Flash Point: 337.3 °C
• PSA: 97.42000
• Density: 1.27 g/cm³
• LogP: 5.13506
• Storage Temp.: Refrigerator
• Solubility.: Acetone (Slightly), Chloroform (Slightly), DMSO (Slightly), Water (Very Slightly
• XLogP3: 4.5
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 5
• Exact Mass: 366.15929460
• Heavy Atom Count: 28
• Complexity: 607

Purity/Quality:

97% ^*data from raw suppliers

Rilpivirine ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiviral Agents
• Canonical SMILES: CC1=CC(=CC(=C1NC2=NC(=NC=C2)NC3=CC=C(C=C3)C#N)C)C=CC#N
• Isomeric SMILES: CC1=CC(=CC(=C1NC2=NC(=NC=C2)NC3=CC=C(C=C3)C#N)C)/C=C/C#N
• Recent ClinicalTrials: A Study to Evaluate Efficacy and Safety of Cabotegravir (CAB) Long Acting (LA) Plus (+) Rilpivirine (RPV) LA Versus BIKTARVY? (BIK) in Participants With Human Immunodeficiency Virus (HIV)-1 Who Are Virologically Suppressed
• Recent EU Clinical Trials: HIV-1 RNA suppression and drug concentrations in semen, cervicovaginal fluid and rectum in HIV-1 infected individuals receiving intramuscular long-acting cabotegravir plus rilpivirine (“CAR-GR Study)
• General Description: 4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethyl-phenyl]amino]pyrimidin-2-yl]amino]benzonitrile (also known as R 278474 or TMC 278) is a diarylpyrimidine (DAPY) derivative identified as a potent HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI). It exhibits strong antiviral activity against HIV-1 wild-type with low nanomolar EC50 values and demonstrates an improved resistance profile, along with reduced cytotoxicity compared to established drugs like etravirine and rilpivirine. 4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethyl-phenyl]amino]pyrimidin-2-yl]amino]benzonitrile exemplifies the successful exploration of the "hydrophobic channel" in HIV-1 RT, contributing to the development of next-generation NNRTIs with enhanced efficacy and safety.

Technology Process of Rilpivirine

There total 36 articles about Rilpivirine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 97.8%

4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile → rilpivirine (500287-72-9)

Guidance literature:

With succinic acid; In acetonitrile; at 60 ℃; Reagent/catalyst; Solvent; Temperature; Large scale; Industrial scale;

Reference yield: 93.9%

(E)- 3-{4-[2-(4-(cyanophenylamino)-1-oxo-pyrimidin-4-yl)amino]-3,5-dimethylphenyl}acrylamide (500288-66-4) → rilpivirine (500287-72-9)

Guidance literature:

With trichlorophosphate; at 20 ℃; Reflux;

Reference yield: 89.6%

(2E)-3-(4-amino-3,5-dimethylphenyl)prop-2-enenitrile hydrochloride (661489-23-2) + 4-[(4-chloro-2-pyrimidinyl)amino]benzonitrile (244768-32-9) → rilpivirine (500287-72-9)

Guidance literature:

(2E)-3-(4-amino-3,5-dimethylphenyl)prop-2-enenitrile hydrochloride; 4-[(4-chloro-2-pyrimidinyl)amino]benzonitrile; In acetonitrile; at 50 ℃; for 24h; Heating / reflux;

With potassium carbonate; In water; acetonitrile; at 40 - 50 ℃; for 1.25 - 1.33h;

In ethanol; for 2h; Heating / reflux;

upstream raw materials:

(cyanomethyl)triphenylphosphonium chloride

4-[4-(4-formyl-2,6-dimethylphenylamino)pyrimidin-2-ylamino]benzonitrile

acrylonitrile

4-((4-((4-bromo-2,6-dimethylphenyl)amino)pyrimidin-2-yl)amino)benzonitrile

Downstream raw materials:

rilpivirine tosylate salt

Rilpivirine hydrochloride

C₂₃H₁₇ClN₆O

Refernces

Discovery of novel diarylpyrimidines as potent HIV-1 NNRTIs by investigating the chemical space of a less explored "hydrophobic channel"

10.1039/c7ob02828h

The study was guided by X-ray structural biology data of HIV-1 RT/NNRTIs complexes and molecular modeling, leading to the design and synthesis of a new series of DAPYs. The purpose was to further investigate the chemical space of the less explored "hydrophobic channel" and to develop NNRTIs with improved resistance profiles. The conclusions drawn from the research indicate that most of the synthesized DAPYs were active against HIV-1 wild-type with low nanomolar EC50 values and displayed reduced cytotoxicity compared to existing drugs like etravirine and rilpivirine. Notably, compounds Z10 and Z13 showed equivalent potency against HIV-1 wild-type as reference drugs efavirenz and etravirine.