Etravirine

HCID 193962

기본 정보

CAS
269055-15-4
표준 SMILES
Cc1cc(C#N)cc(C)c1Oc1nc(Nc2ccc(C#N)cc2)nc(N)c1Br
InChIKey
PYGWGZALEOIKDF-UHFFFAOYSA-N
분자식
C20H15BrN6O
평균 분자량
435.3 g/mol
단동위원소 질량
434.0490712

개요

Etravirine is 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 directly to RT and blocks RNA-dependent and DNA-dependent DNA polymerase activities. It has a role as an antiviral agent and a HIV-1 reverse transcriptase inhibitor. It is an aromatic ether, an organobromine compound, an aminopyrimidine and a dinitrile.

이름 및 식별자

우선 이름
Etravirine
IUPAC
4-[6-amino-5-bromo-2-(4-cyanoanilino)pyrimidin-4-yl]oxy-3,5-dimethylbenzonitrile
영어명
Etravirine
분자식
C20H15BrN6O
분자량
435.28

이름 및 동의어

Etravirine269055-15-4IntelenceTMC-125TMC125TMC 125R1653354-((6-Amino-5-bromo-2-((4-cyanophenyl)amino)pyrimidin-4-yl)oxy)-3,5-dimethylbenzonitrileR-165335Etravirina4-({6-AMINO-5-BROMO-2-[(4-CYANOPHENYL)AMINO]PYRIMIDIN-4-YL}OXY)-3,5-DIMETHYLBENZONITRILETMC125 cpd
이름 더 보기
CS-1948R 165335EtorvulinEtravirine CRSEtravirine PowderSeebio EtravirineEtravirine(TMC-125)Etravirine (R165335
0C50HW4FO1CHEBI:635894-[6-amino-5-bromo-2-(4-cyanoanilino)pyrimidin-4-yl]oxy-3,5-dimethylbenzonitrile4-(6-Amino-5-bromo-2-(4-cyanoanilino)pyrimidin-4-yloxy)-3,5-dimethylbenzonitrileDTXSID301814124-((6-amino-5-bromo-2-((4-cyanophenyl)amino)-4-pyrimidinyl)oxy)-3,5-dimethyl-benzonitrileBenzonitrile, 4-((6-amino-5-bromo-2-((4-cyanophenyl)amino)-4-pyrimidinyl)oxy)-3,5-dimethyl-Benzonitrile, 4-[[6-amino-5-bromo-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3,5-dimethyl-

데이터베이스 식별자

CAS
269055-15-4
PubChem CID
193962
DTXSID
DTXSID30181412
ChEMBL
CHEMBL308954
ChEBI
CHEBI:63589
UNII
0C50HW4FO1
EC Number
682-331-6
Nikkaji
J1.588.786I

물성

구조 계산 물성

XLogP
4.5
극성 표면적
121 Ų
수소 결합 공여자 수
2
수소 결합 수용자 수
7
회전 가능 결합 수
4
무거운 원자 수
28

실험 및 물리화학적 성질

Drugs · 2건

Pharmaceuticals

Pharmaceuticals -> Listed in ZINC15

Human Drugs · 4건

Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Reverse Transcriptase Inhibitors

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

물리화학적 성질

녹는점
265 °C · .265°C (dec.)
끓는 점
637.4 · 637.4±65.0 °C(Predicted)
밀도
1.439 g/cm3 · 1.439 g/cm3
저장 조건
-20 °C · Keep in dark place,Inert atmosphere,Store in freezer, under -20°C
용해도
DMSO (약간 용해됨), 메탄올(약간 용해됨,가열, 초음파 처리)
물리적 상태
고체

화학적 성질

White to Off-White Solid

안전 및 규제

GHS 분류

GHS Classification · 4건

Warning

H302 (90%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P264+P265, P270, P273, P280, P301+P317, P305+P351+P338, P330, P337+P317, P391, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 10 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

유해성 정보

Hazard Classes and CategoriesAcute Tox. 4 (90%)

독성 정보

Hepatotoxicity · 1건

Serum aminotransferase elevations occur in a high proportion of patients on etravirine therapy, but increases above 5 times the upper limit of normal occur in only 2% to 3% of patients; this rate may be higher in patients who have hepatitis C coinfection. In most studies, the rate of liver enzyme elevations was no different in etravirine treated than among in comparator arms. In large clinical trials as well as open access studies, there were no reported instances of clinically apparent liver injury attributed to etravirine.

Drug Induced Liver Injury · 6건

Drug Induced Liver Injury Rank (DILIrank 2.0)

Etravirine

vMost-DILI-concern

8

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

Effects During Pregnancy and Lactation◉ Summary of Use during Lactation

안전 데이터

wgk
WGK 3
Hazard Classifications
Aquatic Acute 1Aquatic Chronic 1
스토리지 클래스
11 - Combustible Solids

화학 및 산업

약리 정보

ATC Code · 3건

J05AG04

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

Protein BindingPlasma protein binding is about 99.9% in vitro. In vitro, 99.6% is bound to albumin, and 97.66% - 99.02% is bound to 1-alpha glycoprotein.
PharmacodynamicsClinical trials have shown no prolongation of QT intervals on electrocardiograms after 8 days of dosing.
Mechanism of Action · 1건

Etravirine exerts its effects via direct inhibition of the reverse transcriptase enzyme of human immunodeficiency virus type 1 (HIV-1). It directly binds reverse transcriptase and consequently blocks DNA-dependent and RNA-dependent polymerase activity. Etravirine does not inhibit human DNA polymerase alpha, beta or gamma.

Biological Half-LifeHalf life of 9.05-41 hours.
Metabolism/MetabolitesMetabolized (in vitro) by the liver CYP450 enzymes: CYP3A4, CYP2C9, CYP2C19. The major metabolites formed by a methyl hydroxylation of the dimethylbenzonitrile moiety retained less than 90% of etravirine's activity.

용도 및 제조

UsesUse (kg; approx.) in Germany (2009): >50
응용 분야 · 2건

개요Etravirine 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. .

용도Etravirine 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.

공급사100 곳

上海阿拉丁生化科技股份有限公司400-6206333 13167063860 · [email protected]
合肥翰刚医药科技有限公司+8618062405514 · [email protected]
Wuhan Chemwonders Technology Inc.027-85778276 · [email protected]
河北展药生物科技有限公司15369953316 +8615369953316 · [email protected]
LGM Pharma1-(800)-881-8210 · [email protected]
추가 설명 · 1건

정의ChEBI: 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

관련 반응

121건

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