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Etravirine

CAS No.
269055-15-4
Chemical Name:
Etravirine
Synonyms
CS-1948;TMC 125;R 165335;Etravirine;Etravirine Powder;Etravirine(TMC-125);Etravirine (R165335;Etravirine 13C 15N2;4-[[6-AMino-5-broMo-2-[(4-cyanophenyl)aMino]-4-pyriMidinyl]oxy]-3,5-diMethyl -;4-[6-amino-5-bromo-2-(4-cyanoanilino)pyrimidin-4-yl]oxy-3,5-dimethylbenzonitrile
CBNumber:
CB51509336
Molecular Formula:
C20H15BrN6O
Molecular Weight:
435.28
MDL Number:
MFCD09837879
MOL File:
269055-15-4.mol
MSDS File:
SDS
Last updated:2023-09-06 17:45:48

Etravirine Properties

Melting point .265°C (dec.)
Boiling point 637.4±65.0 °C(Predicted)
Density 1.439 g/cm3
storage temp. Keep in dark place,Inert atmosphere,Store in freezer, under -20°C
solubility DMSO (Slightly), Methanol (Slightly, Heated, Sonicated)
form Solid
pka 1.23±0.10(Predicted)
color White to Off-White
FDA UNII 0C50HW4FO1
ATC code J05AG04

Pharmacokinetic data

Protein binding 99.9%
Excreted unchanged in urine 0 (1.2% as metabolites)
Biological half-life 30-40 / Probably unchanged

SAFETY

Risk and Safety Statements

Symbol(GHS)  GHS hazard pictograms
GHS09
Signal word  Warning
Hazard statements  H410
Precautionary statements  P273-P391-P501
NFPA 704
0
2 0

Etravirine price More Price(32)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich 901779 4-((6-Amino-5-bromo-2-((4-cyanophenyl)amino)pyrimidin-4-yl)oxy)-3,5-dimethylbenzonitrile 269055-15-4 100MG $138 2023-06-20 Buy
Cayman Chemical 20946 Etravirine ≥95% 269055-15-4 5mg $68 2024-03-01 Buy
Cayman Chemical 20946 Etravirine ≥95% 269055-15-4 10mg $121 2024-03-01 Buy
Cayman Chemical 20946 Etravirine ≥95% 269055-15-4 25mg $268 2024-03-01 Buy
Cayman Chemical 20946 Etravirine ≥95% 269055-15-4 50mg $401 2024-03-01 Buy
Product number Packaging Price Buy
901779 100MG $138 Buy
20946 5mg $68 Buy
20946 10mg $121 Buy
20946 25mg $268 Buy
20946 50mg $401 Buy

Etravirine Chemical Properties,Uses,Production

Description

Etravirine is a second-generation NNRTI. It is indicated for use in combination with other antiretroviral agents for treating HIV-1 infection in treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to the currently available NNRTIs and other antiretroviral agents. The NNRTIs, along with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs), are important components of the combination regimens currently used to treat HIV-1 infection. The NRTIs/NtRTIs act by competing with the natural nucleotide substrates of reverse transcriptase for incorporation into viral DNA and subsequent chain termination. By contrast, the NNRTIs bind to an allosteric site of the enzyme and disrupt the DNA polymerase function by inducing conformational changes to the catalytic site. The allosteric binding nature of NNRTIs generally results in improved safety profile since there is no known human homolog for the drug-binding site of the enzyme.
As with other NNRTIs, etravirine has many drug–drug interactions. It is a substrate of CYP3A4, CYP2C9, and CYP2C19, an inducer of 3A4, and an inhibitor of 2C9 and 2C19. Caution should be used with co-administration of inducers, inhibitors, or substrates of these enzymes. Etravirine can be synthesized starting from 5-bromo-2,4,6-trichloropyrimidine through three successive nucleophilic substitution reactions. Initial displacement with 4-aminobenzonitrile using Hu¨nig’s base, followed by reaction with sodium salt of 4-hydroxy-3,5- dimethylbenzonitrile, and subsequent ammonolysis reaction with ammonia in dioxane under pressure affords etravirine. .

Chemical Properties

White to Off-White Solid

Originator

Janssen (United States)

Uses

Etravirine is a novel HIV reverse transcriptase inhibitor useful in treatment of HIV infection.

Uses

Etravirine (TMC125) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used for the treatment of HIV.

Uses

Etravirine is an antiretroviral (anti-HIV) drug that is part of the non nucleoside reverse transcriptase inhibitor (NNRTIs or Non Nukes) family. It is used together with other antiretrovirals in treatment-experienced adult patients, who have failed previous therapy, and have HIV-1 strains which are resistant to other retrovirals and NNRTIs. Etravirine is used to delay the progression of HIV infection. By using etravirine, your immune system should improve (increase in CD4 + count) and you will be better protected against opportunistic infections.
Etravirine does not cure AIDS or completely kill the HIV virus, but helps to prevent further damage by slowing down the production of new viruses. Treatment with etravirine does not reduce the risk of passing infection on to others. You will still be able to pass HIV by sexual contact, by blood transfer or by sharing needles. You should always use appropriate precautions to prevent passing HIV on to others.

Definition

ChEBI: An aminopyrimidine that consists of 2,6-diaminopyrimidine bearing a bromo substituent at position 5, a 4-cyano-2,6-dimethylphenoxy substituent at position 4 and having a 4-cyanophenyl substituent attached to the 2-amino group. NNRTI of HIV-1, binds directl to RT and blocks RNA-dependent and DNA-dependent DNA polymerase activities

brand name

Intelence

Acquired resistance

Various mutations are associated with a decreased virological response. Single codon substitutions at positions 100, 101 and 181 are considered major mutations. A single K103N mutation is not associated with resistance.

Pharmaceutical Applications

A comprehensive analysis of baseline resistance data from the DUET-1 and DUET-2 studies has identified a list of 17 etravirine resistance associated mutations: V901, A98G, L100L, K101E/H/I, V1061, E138A, V179D/F/T, Y181C/L/V, G190A/S, and M230L. A single K103N mutation is not associated with resistance to etravirine.

Mechanism of action

Etravirine binds directly to reverse transcriptase and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. Etravirine does not inhibit the human DNA polymerases alpha, beta, and gamma.

Pharmacokinetics

Oral absorption: Not known/available
Cmax 200 mg oral twice daily: c. 959 ng/mL
Cmin 200 mg oral twice daily: c. 469 ng/mL
Plasma half-life: c. 36 h
Volume of distribution: Not known/available
Plasma protein binding: >99%
Administration with food improves the bioavailability and reduces interpatient variability. It undergoes oxidative metabolism by cytochrome P450 systems. Around 93.7% and 1.2% of an administered dose can be retrieved in the feces and urine, respectively, mostly as unchanged drug.
Details of distribution into CSF, semen and breast milk and recommendations for dose adjustment in patients with hepatic impairment are not yet available.

Clinical Use

Treatment of HIV-1 infection in adults (in combination with other antiretroviral drugs)

Side effects

In the phase III studies around 15% of patients experienced erythematous or maculopapular rashes of mild or moderate severity; most resolved with continued dosing, but treatment was discontinued in 2% of patients. Rare cases of Stevens– Johnson syndrome have been reported.
Other common adverse events are diarrhea, nausea, headache and fatigue. Dyslipidemia and raised pancreatic amylase occur in some patients.

Synthesis

Only the discovery synthesis and small scale syntheses have been disclosed for this compound in the following scheme. The largest scale synthesis was initiated by the portionwise addition of cyanamide to a solution of the p-cyanoaniline hydrochloride salt 73. The mixture was refluxed in diglyme to give guanidine salt 74 in 85% yield after concentration of the reaction mixture and recrystallization from acetone. Reaction of guanidine 74 with diethylmalonate in the presence of sodium ethoxide in refluxing ethanol gave pyrimidine diol 75 in 57% yield, which upon refluxing in phosphorous oxychloride for 30 min gave dichloride 76 in 97% yield. Bromination of dichloride 76 with NBS in chloroform at room temperature provided bromide 77 in 55% yield. Heating a mixture of the dichlorobromide 77 with the sodium salt of 2,5-dimethyl-4-cyanophenol 78, generated by reaction with sodium hydride in situ) in diglyme and NMP at 155 ??C gave the coupled product 79 in 45% yield. Finally, reaction of the chloride 79 with ammonia in refluxing dioxane (or iPrOH) in a sealed tube gave etravirine (IX) in 41% yield after purification.

Synthesis_269055-15-4

Drug interactions

Potentially hazardous interactions with other drugs
Antibacterials: concentration increased by clarithromycin, also concentration of clarithromycin reduced; concentration of both drugs reduced with rifabutin; avoid concomitant use with rifampicin
. Antivirals: concentration possibly reduced by efavirenz and nevirapine - avoid concomitant use; concentration of fosamprenavir increased, consider reducing fosamprenavir dose; possibly reduces bosutinib and indinavir concentration - avoid concomitant use; concentration of dolutegravir reduced; possibly reduces concentration of maraviroc; concentration reduced by tipranavir and tipranavir concentration increased - avoid concomitant use.
Clopidogrel: possibly reduced antiplatelet effect.
Guanfacine: possibly reduces concentration of guanfacine - increase guanfacine dose.
Orlistat: absorption possibly reduced by orlistat.

Metabolism

Etravirine is extensively metabolised by hepatic microsomal enzymes, mainly by the cytochrome P450 isoenzymes CYP3A4, CYP2C9, and CYP2C19, to substantially less active metabolites.
Unchanged etravirine accounted for 81.2-86.4% of the administered dose in faeces. Unchanged etravirine was not detected in urine.

269055-76-7
269055-15-4
Synthesis of Etravirine from 6-Desamino 6-Chloro Etravirine

Etravirine Preparation Products And Raw materials

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  • Apr 19,2022

View Lastest Price from Etravirine manufacturers

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etravirine pictures 2024-01-12 etravirine
269055-15-4
US $1.00 / mg 1mg 0.99 5ton/month ANHUI SHENGZHIKAI BIOTECHNOLOGY CO.,LTD
etravirine  pictures 2024-01-08 etravirine
269055-15-4
US $4.00 / KG 1KG 99% 50000tons Wuhan Boyuan Import & Export Co., LTD
Etravirine pictures 2023-09-06 Etravirine
269055-15-4
US $50.00 / kg 1kg 99% 10000tons Anhui Ruihan Technology Co., Ltd
  • etravirine pictures
  • etravirine
    269055-15-4
  • US $1.00 / mg
  • 0.99
  • ANHUI SHENGZHIKAI BIOTECHNOLOGY CO.,LTD
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  • etravirine
    269055-15-4
  • US $4.00 / KG
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  • Wuhan Boyuan Import & Export Co., LTD
  • Etravirine pictures
  • Etravirine
    269055-15-4
  • US $50.00 / kg
  • 99%
  • Anhui Ruihan Technology Co., Ltd

Etravirine Spectrum

4-[[6-amino-5-bromo-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3, 5 –dimethylbenzonitrile Etravirine Etravirine(TMC-125) R 165335 TMC 125 4-(6-amino-5-bromo-2-(4-cyanobenzyl)pyrimidin-4-yloxy)-3,5-dimethylbenzonitrile, Etravirine 4-[[6-AMino-5-broMo-2-[(4-cyanophenyl)aMino]-4-pyriMidinyl]oxy]-3,5-diMethyl - 4-[[6-aMino-5-broMo-2-[(4-cyanophenyl)aMino]-4-pyriMidinyl]oxy]-3, 5 –diMethylbenzonitrile/Etravirine 4-[6-amino-5-bromo-2-(4-cyanoanilino)pyrimidin-4-yl]oxy-3,5-dimethylbenzonitrile CS-1948 Etravirine Powder 4-[[6-amino-5-bromo-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3, 5 –dimethylbenzonitrile USP/EP/BP Etravirine (R165335 EtravirineQ: What is Etravirine Q: What is the CAS Number of Etravirine Q: What is the storage condition of Etravirine Q: What are the applications of Etravirine Etravirine 13C 15N2 TIANFU-CHEM - 4-[[6-amino-5-bromo-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3, 5 –dimethylbenzonitrile 269055-15-4 C20H45BrN6O Other APIs All Inhibitors Inhibitors Intermediates & Fine Chemicals Non-nucleoside Reverse Transcriptase Pharmaceuticals