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
이름 더 보기
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
- 형식 전하
- 0
- 복잡도
- 609
실험 및 물리화학적 성질
Drugs
Pharmaceuticals
Pharmaceuticals -> Listed in ZINC15
Human Drugs
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
- 산도 계수 (pKa)
- 1.23 · 1.23±0.10(Predicted)
- 색상
- 흰색에서 황백색까지
- InChI
- InChI=1S/C20H15BrN6O/c1-11-7-14(10-23)8-12(2)17(11)28-19-16(21)18(24)26-20(27-19)25-15-5-3-13(9-22)4-6-15/h3-8H,1-2H3,(H3,24,25,26,27)
- InChIKey
- PYGWGZALEOIKDF-UHFFFAOYSA-N
- SMILES
- C(#N)C1=CC(C)=C(OC2C(Br)=C(N)N=C(NC3=CC=C(C#N)C=C3)N=2)C(C)=C1
화학적 성질
White to Off-White Solid
안전 및 규제
GHS 분류
GHS Classification
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
독성 정보
Hepatotoxicity
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
Drug Induced Liver Injury Rank (DILIrank 2.0)
Etravirine
vMost-DILI-concern
8
Warnings & precautions
DOI:10.1016/j.drudis.2016.02.015
안전 데이터
- wgk
- WGK 3
- Hazard Classifications
- Aquatic Acute 1Aquatic Chronic 1
- 스토리지 클래스
- 11 - Combustible Solids
화학 및 산업
약리 정보
ATC Code
J05AG04
J - Antiinfectives for systemic use
QJ - Antiinfectives for systemic use
Mechanism of Action
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.
FDA Pharmacological Classification
0C50HW4FO1
ETRAVIRINE
Established Pharmacologic Class [EPC] - Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor
Non-Nucleoside Analog [EXT]
Mechanisms of Action [MoA] - Non-Nucleoside Reverse Transcriptase Inhibitors
Mechanisms of Action [MoA] - Cytochrome P450 3A Inducers
Absorption, Distribution and Excretion
Maximum oral absorption is achieved in 2.5-4 hours. Absorption is unaffected by the concomitant use of oral ranitidine or omeprazole, which decrease gastric acidity. Administration under fasting conditions resulted in a near 50% decrease in systemic exposure (AUC) when compared to administration after a meal.
After a 800mg dose of radio-labelled etraverine, 93.7% was found to undergo fecal elimination, with 81.2% - 86.4% eliminated unchanged. 1.2% of the dose was renally eliminated, changed. Etravirine is dialyzable (hemodialysis).
Distribution of etravirine into compartments other than plasma has not been evaluated in humans.
Renal clearance of etravirine is negligible (<1.2%), thus no dose adjustments are required in patients with renal impairment. Clearance is shown to be reduced in patients with Hepatitis B and/or co-infection, however, the safety profile of etravirine does not call for dosage adjustments.
용도 및 제조
응용 분야
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.
상·하류 제품 정보
상류 원료
공급사100 곳
추가 설명
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
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