硫酸阿巴卡韦 | 188062-50-2

• 物质功能分类: 原料药 - 人工合成抗感染类药 - 抗病毒类药
• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 中文名称: 硫酸阿巴卡韦
• 中文别名: (1S,4R)-4-[2-氨基-6-(环丙基氨基)-9H-嘌呤-9-基]-2-环戊烯-1-甲醇硫酸盐；阿巴卡韦硫酸盐；赛进；阿波卡伟
• 英文名称: abacavir sulfate
• 英文别名: abacavir；[(1S,4R)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]cyclopent-2-en-1-yl]methanol;sulfuric acid
• CAS: 188062-50-2
• 化学式: 2C₁₄H₁₈N₆O*H₂O₄S
• 分子量: 670.753
• InChiKey: MBFKCGGQTYQTLR-SCYNACPDSA-N

物化性质

• 熔点：
  222-225°C
• 溶解度：
  H2O：≥17mg/mL
• 颜色/状态：
  White to off-white solid

计算性质

• 辛醇/水分配系数(LogP)：
  0.44
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  185
• 氢给体数：
  5
• 氢受体数：
  10

ADMET

代谢

阿巴卡韦部分通过醇脱氢酶（形成5'-羧酸）和葡萄糖醛酸化（形成5'-葡萄糖醛酸苷）进行代谢。

Abacavir is partially metabolized by alcohol dehydrogenase (to form the 5'-carboxylic acid) and glucuronidation (to form the 5'-glucuronide).

来源:Hazardous Substances Data Bank (HSDB)

代谢

阿巴卡韦的代谢命运尚未完全确定，但该药物在肝脏中代谢。阿巴卡韦通过醇脱氢酶代谢形成5-羧酸，通过葡萄糖醛酸转移酶代谢形成5-葡萄糖苷酸；这些代谢物似乎没有抗病毒活性。细胞色素P450同工酶在阿巴卡韦代谢中的参与是有限的。

The metabolic fate of abacavir has not been fully determined, but the drug is metabolized in the liver. Abacavir is metabolized by alcohol dehydrogenase to form the 5-carboxylic acid and by glucuronyltransferase to form the 5-glucuronide; these metabolites do not appear to have any antiviral activity. Any involvement of cytochrome p450 isoenzymes in the metabolism of abacavir is limited.

来源:Hazardous Substances Data Bank (HSDB)

代谢

细胞内，阿巴卡韦通过腺苷酸转移酶磷酸化生成阿巴卡韦一磷酸盐；随后，在细胞质酶催化的反应中，阿巴卡韦一磷酸盐转化为卡波韦一磷酸盐，然后通过细胞激酶进一步转化为卡波韦三磷酸盐。阿巴卡韦到卡波韦三磷酸盐的细胞内（宿主细胞）转化对于该药物的 抗病毒活性是必要的。在体外，卡波韦三磷酸盐在CD4+ CEM细胞中的半衰期为3.3小时。

Intracellularly, abacavir is phosphorylated to abacavir monophosphate by adenosine phosphotransferase; abacavir monophosphate is then converted to carbovir monophosphate in a reaction catalyzed by cytosolic enzymes and then to carbovir triphosphate by cellular kinases. Intracellular (host cell) conversion of abacavir to carbovir triphosphate is necessary for the antiviral activity of the drug. The in vitro intracellular half-life of carbovir triphosphate in CD4+ CEM cells is 3.3 hours.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：阿巴卡韦在母乳中以小量出现。关于其在哺乳期使用的安全性信息非常有限。在美国和其他可以获取清洁水源和负担得起的替代喂养的国家，建议感染HIV的母亲不要母乳喂养婴儿，以避免HIV-1感染的后天传播。通过抗逆转录病毒治疗实现并维持病毒载量抑制，可以将母乳喂养传播风险降低到小于1%，但并非零。在抗逆转录病毒治疗下，病毒载量持续不可检测的HIV感染者如果选择母乳喂养，应支持这一决定。 ◉ 对母乳喂养婴儿的影响：一名HIV阳性母亲每天服用一次含有多替拉韦50mg、硫酸阿巴卡韦600mg和拉米夫定300mg（特鲁迈克）的复合片剂。她的婴儿大约纯母乳喂养了30周，然后又部分母乳喂养了大约20周。未观察到明显的副作用。 ◉ 对泌乳和母乳的影响：在接受高效抗逆转录病毒治疗的男性中报告了男性乳房发育。男性乳房发育最初是单侧的，但在大约一半的病例中进展为双侧。未观察到血清催乳素的变化，即使继续用药，通常也会在一年内自发解决。一些病例报告和体外研究建议蛋白酶抑制剂可能会在某些男性患者中引起高催乳素血症和乳汁分泌过多，尽管这一点存在争议。这些发现与哺乳母亲的相关性尚不清楚。已建立泌乳的母亲催乳素水平可能不会影响她的哺乳能力。

◉ Summary of Use during Lactation:Abacavir appears in breastmilk in small quantities. Very little information is available on the safety of its use during breastfeeding. In the US and other countries where access to clean water and affordable replacement feeding are available, it is recommended that mothers living with HIV not breastfeed their infants to avoid postnatal transmission of HIV-1 infection. Achieving and maintaining viral suppression with antiretroviral therapy decreases breastfeeding transmission risk to less than 1%, but not zero. Individuals with HIV who are on antiretroviral therapy with a sustained undetectable viral load and who choose to breastfeed should be supported in this decision. ◉ Effects in Breastfed Infants:An HIV-positive mother took a combination tablet containing dolutegravir 50 mg, abacavir sulfate 600 mg and lamivudine 300 mg (Triumeq) once daily. Her infant was exclusively breastfed for about 30 weeks and partially breastfed for about 20 weeks more. No obvious side effects were noted. ◉ Effects on Lactation and Breastmilk:Gynecomastia has been reported among men receiving highly active antiretroviral therapy. Gynecomastia is unilateral initially, but progresses to bilateral in about half of cases. No alterations in serum prolactin were noted and spontaneous resolution usually occurred within one year, even with continuation of the regimen. Some case reports and in vitro studies have suggested that protease inhibitors might cause hyperprolactinemia and galactorrhea in some male patients, although this has been disputed. The relevance of these findings to nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 相互作用

同时使用乙醇与阿巴卡韦可能会导致阿巴卡韦的浓度和半衰期增加，这是由于酒精脱氢酶通过共同代谢途径竞争所致。

Concurrent use /of ethanol/ with abacavir may result in increased concentrations and half-life of abacavir as a result of competition for common metabolic pathways via alcohol dehydrogenase.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在接受口服美沙酮维持治疗的稳定患者中，开始每日两次600毫克阿巴卡韦治疗，美沙酮的清除率增加了22%；在大多数患者中，清除率的增加在临床上不会显著；少数患者可能需要增加美沙酮的剂量。

Methadone clearance increased 22% in patients stabilized on oral methadone maintenance therapy who started abacavir therapy with 600 mg twice daily; increase in clearance will not be clinically significant in the majority of patients; methadone dosage increase may be required in a small number of patients.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

基本治疗：建立专利气道。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，协助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要进行治疗……。监测休克，如有必要进行治疗……。预见并治疗癫痫发作……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用生理盐水连续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

高级治疗：对于昏迷、严重肺水肿或呼吸停止的患者，考虑进行口咽或鼻咽插管以控制气道。使用带有气囊面罩的装置进行正压通气技术可能有益。监测心率和必要时治疗心律失常。 ... 开始静脉输液，使用5%葡萄糖盐水/生理盐水： "保持开放"，最低流速/。如果出现低血容量的迹象，使用乳酸钠林格氏液。注意液体过载的迹象。考虑使用药物治疗肺水肿。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象。 ... 使用地西泮（安定）治疗癫痫。使用丙美卡因氢氯化物协助眼部冲洗。 /毒药A和B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在口服600毫克放射性阿巴卡韦后，82.2%的剂量通过尿液排出，16%的剂量通过粪便排出。尿液中的5-羧酸代谢物、5-葡萄糖苷酸代谢物和未改变的阿巴卡韦分别占回收放射性活性的30%、36%和1.2%；未识别的次要代谢物占尿液回收放射性活性的15%。

Following oral administration of a 600-mg dose of radiolabeled abacavir, 82.2% of the dose is excreted in urine and 16% of the dose is excreted in feces. The 5-carboxylic acid metabolite, 5-glucuronide metabolite, and unchanged abacavir accounted for 30, 36, and 1.2%, respectively, of recovered radioactivity in urine; unidentified minor metabolites accounted for 15% of recovered radioactivity in urine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

尚不清楚阿巴卡韦是否分布到人乳中；该药物在大鼠乳汁中有分布。

It is not known whether abacavir is distributed into human milk; the drug is distributed into milk in rats.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

Abacavir 在大鼠体内可通过胎盘。

Abacavir crosses the placenta in rats.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

阿巴卡韦的口服生物利用度很高，无论是否与食物同服；脑脊液与血浆的AUC比值大约为0.3。

The oral bioavailability of abacavir is high with or without food; the CSF-to-plasma AUC ratio is approximately 0.3.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S36/37
• 危险类别码：
  R40,R63
• WGK Germany：
  3
• 海关编码：
  2933595960
• 包装等级：
  III
• 危险类别：
  6.1
• 危险性防范说明：
  P280,P305+P351+P338
• 危险品运输编号：
  2811
• 危险性描述：
  H317,H319,H341,H350,H360
• 储存条件：
  -20°C冷冻库

SDS

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SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : Abacavir sulfate
REACH No. : A registration number is not available for this substance as the substance
or its uses are exempted from registration, the annual tonnage does not
require a registration or the registration is envisaged for a later
registration deadline.
CAS-No. : 188062-50-2
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

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SECTION 2: Hazards identification
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008
Carcinogenicity (Category 2), H351
Reproductive toxicity (Category 2), H361
For the full text of the H-Statements mentioned in this Section, see Section 16.
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Xn Harmful R40, R63
For the full text of the R-phrases mentioned in this Section, see Section 16.
Label elements
Labelling according Regulation (EC) No 1272/2008
Pictogram
Signal word Warning
Hazard statement(s)
H351 Suspected of causing cancer.
H361 Suspected of damaging fertility or the unborn child.
Precautionary statement(s)
P281 Use personal protective equipment as required.
Supplemental Hazard none
Statements
Other hazards - none

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SECTION 3: Composition/information on ingredients
Substances
Synonyms : Abacavir hemisulfate
Formula : C14H18N6O · 0.5 H2SO4
Molecular Weight : 335,37 g/mol
CAS-No. : 188062-50-2
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
Abacavir sulfate
CAS-No. 188062-50-2 Carc. 2; Repr. 2; H351, H361 <= 100 %
For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16

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SECTION 4: First aid measures
Description of first aid measures
General advice
Consult a physician. Show this safety data sheet to the doctor in attendance.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Consult a physician.
In case of eye contact
Flush eyes with water as a precaution.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.
Most important symptoms and effects, both acute and delayed
The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in
section 11
Indication of any immediate medical attention and special treatment needed
no data available

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SECTION 5: Firefighting measures
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
no data available
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

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SECTION 6: Accidental release measures
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure
adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.
For personal protection see section 8.
Environmental precautions
Prevent further leakage or spillage if safe to do so. Do not let product enter drains.
Methods and materials for containment and cleaning up
Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed
containers for disposal.
Reference to other sections
For disposal see section 13.

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SECTION 7: Handling and storage
Precautions for safe handling
Avoid contact with skin and eyes. Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed.
For precautions see section 2.2.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Recommended storage temperature: 2 - 8 °C
Specific end use(s)
A part from the uses mentioned in section 1.2 no other specific uses are stipulated

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SECTION 8: Exposure controls/personal protection
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and
at the end of workday.
Personal protective equipment
Eye/face protection
Safety glasses with side-shields conforming to EN166 Use equipment for eye protection tested
and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique
(without touching glove's outer surface) to avoid skin contact with this product. Dispose of
contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and
the standard EN 374 derived from it.
Body Protection
impervious clothing, The type of protective equipment must be selected according to the
concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
Where risk assessment shows air-purifying respirators are appropriate use a full-face particle
respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering
controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use
respirators and components tested and approved under appropriate government standards such
as NIOSH (US) or CEN (EU).
Control of environmental exposure
Prevent further leakage or spillage if safe to do so. Do not let product enter drains.

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SECTION 9: Physical and chemical properties
Information on basic physical and chemical properties
a) Appearance Form: solid
b) Odour no data available
c) Odour Threshold no data available
d) pH no data available
e) Melting point/freezing no data available
point
f) Initial boiling point and no data available
boiling range
g) Flash point no data available
h) Evapouration rate no data available
i) Flammability (solid, gas) no data available
j) Upper/lower no data available
flammability or
explosive limits
k) Vapour pressure no data available
l) Vapour density no data available
m) Relative density no data available
n) Water solubility no data available
o) Partition coefficient: n- no data available
octanol/water
p) Auto-ignition no data available
temperature
q) Decomposition no data available
temperature
r) Viscosity no data available
s) Explosive properties no data available
t) Oxidizing properties no data available
Other safety information
no data available

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SECTION 10: Stability and reactivity
Reactivity
no data available
Chemical stability
Stable under recommended storage conditions.
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
Strong oxidizing agents
Hazardous decomposition products
Other decomposition products - no data available
In the event of fire: see section 5

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SECTION 11: Toxicological information
Information on toxicological effects
Acute toxicity
no data available
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitisation
no data available
Germ cell mutagenicity
no data available
Carcinogenicity
Limited evidence of carcinogenicity in animal studies
IARC: No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
Suspected human reproductive toxicant
Specific target organ toxicity - single exposure
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Additional Information
RTECS: Not available
Hypersensitivity reactions include:, Fever, Rash, Ingestion may cause gastrointestinal irritation, nausea,
vomiting and diarrhoea., Fatigue, Respiratory disorder

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SECTION 12: Ecological information
Toxicity
no data available
Persistence and degradability
no data available
Bioaccumulative potential
no data available
Mobility in soil
no data available
Results of PBT and vPvB assessment
PBT/vPvB assessment not available as chemical safety assessment not required/not conducted
Other adverse effects
no data available

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SECTION 13: Disposal considerations
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company. Dissolve or mix the material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.
Contaminated packaging
Dispose of as unused product.

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SECTION 14: Transport information
UN number
ADR/RID: - IMDG: - IATA: -
UN proper shipping name
ADR/RID: Not dangerous goods
IMDG: Not dangerous goods
IATA: Not dangerous goods
Transport hazard class(es)
ADR/RID: - IMDG: - IATA: -
Packaging group
ADR/RID: - IMDG: - IATA: -
Environmental hazards
ADR/RID: no IMDG Marine pollutant: no IATA: no
Special precautions for user
no data available

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SECTION 15 - REGULATORY INFORMATION
N/A

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

硫酸阿巴卡韦简介

硫酸阿巴卡韦是抗病毒药物阿巴卡韦的硫酸盐，药理作用与阿巴卡韦相同，由英国葛兰素威康（Glaxo-Wellcome）公司研发成功。1998年12月，美国食品与药品管理局（FDA）批准其上市销售，商品名为Ziagen。本品是一种核苷类逆转录酶抑制剂（NRTI），通过抑制HIV逆转录酶，引起断链，阻止病毒复制而起效。研究显示，本品与其他核苷类逆转录酶抑制剂如地丹诺辛 (didanosine)、扎西他宾 (zalcitabine)、拉米夫定 (lamivudine) 和司他夫定 (stavudine) 合用时，疗效具有相加作用；与齐多夫定 (zidovudine) 合用有协同作用。这为治疗HIV感染提供了一种三重治疗的新方法，并使得蛋白酶抑制剂和非核苷逆转录酶抑制剂在临床用药中保持可选择性。

不良反应

2004年4月，美国FDA批准硫酸阿巴卡韦联合其他药物用于抗HIV的感染。2003年，其销售收入为1.67亿英镑。2008年2月份，美国食品与药品管理局修订了艾滋病抗病毒治疗指南，阿巴卡韦成为初次治疗患者中的一种首选抗病毒药物。该选择除了因其抗病毒效果与泰诺福韦相近、对线粒体损害较小、从而减少脂肪消耗、胰腺炎、神经炎和乳酸酸中毒等不良反应外，还在于用药前筛查超敏反应的基因HLA-B5701，在国外应用于临床时，阴性者应用该药后一般不会发生超敏反应，安全性大大提高。2008年5月，美国食品药品管理局（FDA）发布了关于阿巴卡韦（Abacavir）和去羟肌苷（Didanosine）的早期安全性警示，称服用这两种药物的患者存在心脏病发作、心肌梗死的风险。然而，阿巴卡韦制药商葛兰素史克公司收到D:A:D研究分析初步结果后，并未发现该药会增加心脏病发作或心肌梗死的风险。

生物活性

阿巴卡韦（1592U89）是一种常用的核苷类似物，具有抗HIV-1病毒活性。阿巴卡韦是鸟嘌呤的类似物，其靶点为病毒的反转录酶。

Target	Value
HIV-1 reverse-transcriptase

靶点

阿巴卡韦以病毒逆转录酶为靶点，是一种鸟苷（一种嘌呤）类似物。

反应信息

• 作为反应物：
  描述：

  硫酸阿巴卡韦 在 吡啶 、 咪唑 、 triethylamine tris(hydrogen fluoride) 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 21.0h， 生成 (-)-N-{6-(cyclopropylamino)-9-[(1R,4S)-4-(hydroxymethyl)cyclopent-2-enyl]-9H-purin-2-yl}isobutyramide
  参考文献：
  名称：

  化学掺入链终止核苷类似物作为 3'-阻断 DNA 损伤及其通过人 ERCC1-XPF 核酸内切酶去除

  摘要：

  缺乏 3'-羟基的核苷/核苷酸类似物被广泛用于 HIV 治疗。这些链终止核苷类似物 (CTNA) 在掺入生长的 DNA 后会阻止 DNA 合成，从而产生抗病毒作用。然而，它们也被认为是 DNA 损伤剂，据报道，酪氨酰 DNA 磷酸二酯酶 1（一种 DNA 修复酶）能够去除 DNA 的此类 CTNA 修饰。在这里，我们合成了代表性 CTNA 的亚磷酰胺构件，例如阿昔洛韦、阿巴卡韦、卡波韦和拉米夫定，并且在固体支持物上成功合成了具有 3'-CTNA 的寡核苷酸。使用化学合成的寡核苷酸，我们研究了人类切除修复交叉互补蛋白 1-色素干皮病 F 组（ERCC1-XPF）核酸内切酶对 DNA 中 3'-CTNA 的切除，该酶是核苷酸切除修复途径的主要成分之一。生化分析表明 ERCC1-XPF 核酸内切酶在 3'-阻断 CTNAs 上游 2-7 nt 处切割，并且在去除 CTNAs 后重新开始 Klenow

  DOI：

  10.3390/molecules21060766
• 作为产物：
  描述：

  阿巴卡韦 在 硫酸 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 硫酸阿巴卡韦
  参考文献：
  名称：

  [EN] NOVEL CRYSTALLINE FORMS OF ABACAVIR SULFATE
  [FR] NOUVELLES FORMES CRISTALLINES DE SULFATE D'ABACAVIR

  摘要：

  本发明涉及阿巴卡韦硫酸盐的新型晶体形式，以及其制备方法和含有它们的药物组合物。

  公开号：

  WO2004089952A1

文献信息

• [EN] SPIROCYCLIC HETEROCYCLE COMPOUNDS USEFUL AS HIV INTEGRASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES SPIROCYCLIQUES UTILES COMME INHIBITEURS DU VIH
  申请人：MERCK SHARP & DOHME

  公开号：WO2016094198A1

  公开（公告）日：2016-06-16

  The present invention relates to Spirocyclic Heterocycle Compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein A, B, X, R1, R2, R3 and R4 are as defined herein. The present invention also relates to compositions comprising at least one Spirocyclic Heterocycle Compound, and methods of using the Spirocyclic Heterocycle Compounds for treating or preventing HIV infection in a subject.

  本发明涉及式(I)的螺环杂环化合物及其药学上可接受的盐，其中A、B、X、R1、R2、R3和R4如本文所定义。本发明还涉及包含至少一种螺环杂环化合物的组合物，以及使用螺环杂环化合物治疗或预防受试者的HIV感染的方法。
• [EN] HETEROCYCLIC COMPOUNDS AS HIV PROTEASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES EN TANT QU'INHIBITEURS DE LA PROTÉASE DU VIH
  申请人：MERCK SHARP & DOHME

  公开号：WO2018106519A1

  公开（公告）日：2018-06-14

  The present invention is directed to compounds of Formula (I), pharmaceutical compositions comprising the same, and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS.

  本发明涉及式(I)的化合物，包括相同的药物组合物，以及它们在抑制HIV蛋白酶、抑制HIV复制、预防HIV感染、治疗HIV感染以及预防、治疗和延缓艾滋病的发病或进展中的用途。
• [EN] PIPERIDINE OR PIPERAZINE LINKED IMIDAZOLE AND TRIAZOLE DERIVATIVES AND METHODS OF USE THEREOF FOR IMPROVING THE PHARMACOKINETICS OF A DRUG<br/>[FR] DÉRIVÉS D'IMIDAZOLE ET DE TRIAZOLE LIÉS À LA PIPÉRIDINE OU LA PIPÉRAZINE ET LEURS PROCÉDÉS D'UTILISATION POUR AMÉLIORER LA PHARMACOCINÉTIQUE D'UN MÉDICAMENT
  申请人：MERCK SHARP & DOHME

  公开号：WO2015070367A1

  公开（公告）日：2015-05-21

  The piperidine or piperazine linked imidazole and triazole derivatives, compositions comprising said compounds, alone or in combination with other drugs, and methods of using the compounds for improving the pharmacokinetics of a drug are provided. The compounds of the invention are useful in human and veterinary medicine for inhibiting CYP3A4 and for improving the pharmacokinetics of a therapeutic compound that is metabolized by CYP3A4.

  提供了与哌啶或哌嗪连接的咪唑和三唑衍生物，包括所述化合物的组合物，单独或与其他药物结合使用的方法，以及用于改善药物的药代动力学的化合物的方法。该发明的化合物在人类和兽医学中用于抑制CYP3A4并改善由CYP3A4代谢的治疗化合物的药代动力学。
• [EN] MACROCYCLIC COMPOUNDS AS HIV INTEGRASE INHIBITORS<br/>[FR] COMPOSÉS MACROCYCLIQUES EN TANT QU'INHIBITEURS DE L'INTÉGRASE DU VIH
  申请人：MERCK SHARP & DOHME

  公开号：WO2014011769A1

  公开（公告）日：2014-01-16

  The present invention relates to Macrocyclic Compounds. The present invention also relates to compositions comprising at least one Macrocyclic Compound, and methods of using the Macrocyclic Compounds for treating or preventing HIV infection in a subject.

  本发明涉及大环化合物。本发明还涉及包含至少一种大环化合物的组合物，以及利用这些大环化合物治疗或预防受试者的HIV感染的方法。
• MACROCYCLIC COMPOUNDS AS HIV INTEGRASE INHIBITORS
  申请人：MERCK SHARP & DOHME CORP.

  公开号：US20150203512A1

  公开（公告）日：2015-07-23

  The present invention relates to Macrocyclic Compounds. The present invention also relates to compositions comprising at least one Macrocyclic Compound, and methods of using the Macrocyclic Compounds for treating or preventing HIV infection in a subject.

  本发明涉及大环化合物。本发明还涉及包含至少一种大环化合物的组合物，以及利用这些大环化合物治疗或预防受试者的HIV感染的方法。