Etravirine

Base Information

• Chemical Name: Etravirine
• CAS No.: 269055-15-4
• Deprecated CAS: 394729-17-0
• Molecular Formula: C20H15BrN6O
• Molecular Weight: 435.283
• European Community (EC) Number: 682-331-6
• UNII: 0C50HW4FO1
• DSSTox Substance ID: DTXSID30181412
• Nikkaji Number: J1.588.786I
• Wikipedia: Etravirine
• Wikidata: Q414762
• NCI Thesaurus Code: C73195
• RXCUI: 475969
• Metabolomics Workbench ID: 62857
• ChEMBL ID: CHEMBL308954
• Mol file: 269055-15-4.mol

Synonyms:4-((6-amino-5-bromo-2-((4-cyanophenyl)amino)-4-pyrimidinyl)oxy)-3,5-dimethyl-benzonitrile;benzonitrile, 4-((6-amino-5-bromo-2-((4-cyanophenyl)amino)-4-pyrimidinyl)oxy)-3,5-dimethyl-;etravirine;Intelence;R165335;TMC 125;TMC-125;TMC125 cpd

Chemical Property of Etravirine

Chemical Property:

• Appearance/Colour: white to off-white solid
• Vapor Pressure: 3.82E-16mmHg at 25°C
• Melting Point: 265oC (dec.)
• Refractive Index: 1.702
• Boiling Point: 637.4 °C at 760 mmHg
• PKA: 1.23±0.10(Predicted)
• Flash Point: 339.3 °C
• Density: 1.57 g/cm³
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO (Slightly), Methanol (Slightly, Heated, Sonicated)
• XLogP3: 4.5
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 4
• Exact Mass: 434.04907
• Heavy Atom Count: 28
• Complexity: 609

Purity/Quality:

99% ^*data from raw suppliers

Etravirine ^*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(=C1OC2=NC(=NC(=C2Br)N)NC3=CC=C(C=C3)C#N)C)C#N
• Recent ClinicalTrials: TMC125-TiDP35-C239 - Continued Access to Etravirine (ETR) in Treatment Experienced HIV-1 Infected Participants
• Recent EU Clinical Trials: Clinical trial - phase II - to test safety and efficay of Etravirine's treatment in Friedreich Ataxia's patients
• General Description: 4-[[6-Amino-5-bromo-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3,5-dimethylbenzonitrile (also known as Intelence, R 165335, or TMC 125) is a diarylpyrimidine (DAPY) derivative that functions as a potent non-nucleoside reverse transcriptase inhibitor (NNRTI) against HIV-1. It exhibits strong antiviral activity against wild-type HIV-1 with low nanomolar EC50 values while demonstrating reduced cytotoxicity compared to other NNRTIs like etravirine and rilpivirine. 4-[[6-amino-5-bromo-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3, 5 –dimethylbenzonitrile's efficacy stems from its optimized interaction with the hydrophobic channel of HIV-1 reverse transcriptase, contributing to an improved resistance profile.

Technology Process of Etravirine

There total 28 articles about Etravirine 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: 92.82%

4-{6-amino-2-[(4-cyanophenyl)amino]pyrimidin-4-yloxy}-3,5-dimethylbenzenecarbonitrile → etravirine (269055-15-4,394729-17-0)

Guidance literature:

4-{6-amino-2-[(4-cyanophenyl)amino]pyrimidin-4-yloxy}-3,5-dimethylbenzenecarbonitrile; With bromine; In propan-1-ol; at 5 - 20 ℃;

With sodium hydroxide; In propan-1-ol; water; at 0 - 20 ℃; Product distribution / selectivity;

Reference yield: 89.0%

4-((4-amino-5-bromo-6-chloropyrimidin-2-yl)amino)benzonitrile (1398507-09-9) + 3,5-dimethyl-4-hydroxybenzonitrile (4198-90-7) → etravirine (269055-15-4,394729-17-0)

Guidance literature:

3,5-dimethyl-4-hydroxybenzonitrile; With potassium carbonate; potassium iodide; In 1-methyl-pyrrolidin-2-one; at 0 - 5 ℃; for 0.166667h; Inert atmosphere;

4-((4-amino-5-bromo-6-chloropyrimidin-2-yl)amino)benzonitrile; In 1-methyl-pyrrolidin-2-one; at 10 - 120 ℃; for 26.5h; Time; Temperature; Reagent/catalyst; Concentration; Inert atmosphere;

Reference yield: 56.0%

C25H22BrN5O3 (1616667-63-0) → etravirine (269055-15-4,394729-17-0)

Guidance literature:

C₂₅H₂₂BrN₅O₃; With silver(II) fluoride; Inert atmosphere; Glovebox;

With ammonia; In water; isopropyl alcohol; at 80 ℃; for 0.5h;

With hydrogenchloride; In water; at 0.25 ℃; for 0.5h;

upstream raw materials:

4-[[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)-6-chloro-2-pyrimidinyl]amino]-benzonitrile

4-(4,6-dichloropyrimidine-2-yl-amino)benzonitrile

4-((4,6-dihydroxypyrimidine-2-yl)amino)benzonitrile

4-[[(5-bromo-4,6-dichloro)-2-pyrimidinyl]amino]benzonitrile

Downstream raw materials:

etravirine tosylatee salt

etravirine phosphate

4-[[4-amino-5-chloro-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino]-benzonitrile

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.