醋丁洛尔盐酸盐 | 34381-68-5

• 物质功能分类: 生物化工 - 抑制剂 - 神经信号通路(Neuronal Signaling)
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 醋丁洛尔盐酸盐
• 中文别名: N-[3-乙酰基-4-[2-羟基-3-[(异丙基)氨基]丙氧基]苯基]丁酰胺盐酸盐；盐酸醋丁洛尔；奥替溴胺
• 英文名称: acebutolol hydrochloride
• 英文别名: N-(3-acetyl-4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl)butanamide hydrochloride；N-[3-acetyl-4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]butanamide;hydron;chloride
• CAS: 34381-68-5
• 化学式: C₁₈H₂₈N₂O₄*ClH
• mdl: MFCD00078860
• 分子量: 372.892
• InChiKey: KTUFKADDDORSSI-UHFFFAOYSA-N

物化性质

• 熔点：
  141-1430C
• 溶解度：
  易溶于水和乙醇（96%），极微溶于丙酮和二氯甲烷。
• 颜色/状态：
  White or slightly off-white, crystalline powder
• 碰撞截面：
  188.3 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]
• 稳定性/保质期：
  如果按照规格正确使用和储存，则不会发生分解，也未发现有已知的危险反应。

计算性质

• 辛醇/水分配系数(LogP)：
  1.53
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.555
• 拓扑面积：
  92.2
• 氢给体数：
  3
• 氢受体数：
  5

ADMET

代谢

Acebutolol is rapidly and extensively metabolized in the liver. Acebutolol undergoes extensive hydrolysis of the butyramide group to form the desbutyl primary amine, acetolol, which is almost completely converted via N-acetylation to diacetolol. The extent of metabolism of acebutolol to diacetolol appears to be independent of the genetic acetylator phenotype of the patient. Diacetolol is equipotent to acebutolol and has a similar pharmacologic profile. 奥昔布洛尔在肝脏中迅速且广泛地被代谢。奥昔布洛尔经过丁酰胺基团的广泛水解，形成去丁基一级胺，醋洛尔，后者几乎完全通过N-乙酰化转化为二醋洛尔。奥昔布洛尔到二醋洛尔的代谢程度似乎与患者的遗传乙酰化酶表型无关。二醋洛尔与奥昔布洛尔等效，并具有类似的药理特性。

Acebutolol is rapidly and extensively metabolized in the liver. Acebutolol undergoes extensive hydrolysis of the butyramide group to form the desbutyl primary amine, acetolol, which is almost completely converted via N-acetylation to diacetolol. The extent of metabolism of acebutolol to diacetolol appears to be independent of the genetic acetylator phenotype of the patient. Diacetolol is equipotent to acebutolol and has a similar pharmacologic profile.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

当同时给予醋丁洛尔和一种去甲肾上腺素耗竭药物（例如，利血平）时，药物的效果可能是累加的。

When acebutolol and a catecholamine-depleting drug (eg, reserpine) are administered concomitantly, the effects of the drugs may be additive.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

当给予降压药或与其他降压药同时使用时，降压效果可能会增加。这种效果通常被用于治疗优势，但必须仔细调整剂量。尚未观察到醋丁洛尔与氢氯噻嗪或肼苯哒嗪之间的显著药代动力学相互作用。

When acebutolol is administered with diuretics or other hypotensive agents, the hypotensive effect may be increased. This effect usually is used to therapeutic advantage, but careful adjustment of dosage is necessary when these drugs are used concomitantly. No substantial pharmacokinetic interactions between acebutolol and hydrochlorothiazide or hydralazine have been observed.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

醋丁洛尔减少了格列本脲对II型糖尿病患者的降糖作用，可能是通过减少胰岛素分泌。非甾体抗炎药减弱了β-肾上腺素能受体阻滞剂（即洛尔类药物）的降压效果。

Acebutolol has decreased the hypoglycemic action of glyburide in type II diabetic patients, presumably by decreasing insulin secretion. Nonsteroidal anti-inflammatory agents have blunted the hypotensive effects of beta-adrenergic blocking agents.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在用β2-肾上腺素能受体阻断剂布托啡和β-受体非特异性阻断剂普萘洛尔预处理的大鼠中，发现异烟肼诱发的惊厥发作有所延迟。在这些动物中，惊厥反应以剂量依赖性方式被抑制。即使是在惊厥发作后，这些化合物仍然有效。β1-受体阻断剂醋丁洛尔仅在注射后挑战前能保护大鼠。在用γ-氨基丁酸提高剂氨基氧乙酸预处理的大鼠中，发现醋丁洛尔和普萘洛尔的抗惊厥效果增强，而布托啡的效果则没有增强。这些发现表明，氨基氧乙酸的γ-氨基丁酸介导的抗惊厥作用似乎与β1-阻断的结果相加，而不是β2-阻断的结果。

A delay in the onset of isoniazid induced convulsions was found in rats pretreated with the beta 2-adrenoceptor blocker, butoxamine, and the nonspecific beta-blocker, propranolol. In these animals the convulsive responses were inhibited in a dose dependent manner. These compounds were found to be effective even after the induction of convulsions. The beta-1-blocker, acebutolol was able to protect rats only when injected prior to the challenge. The anticonvulsant effect of acebutolol and propranolol but not that of butoxamine was found to be enhanced in animals pretreated with a gamma-aminobutyric acid elevating agent, aminooxyacetic acid. The findings indicate that the gamma-aminobutyric acid mediated anticonvulsant action of aminooxyacetic acid seems to be additive with that resulting from beta-1 but not beta-2-blockade.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

与甲苯磺丁脲和华法林进行的药物相互作用研究表明，这些化合物对甲苯磺丁脲和华法林的疗效没有影响。地高辛和氢氯噻嗪的血浆水平并未受到同时给予Sectral（醋丁洛尔）的影响。同时给予氢氯噻嗪、肼屈嗪、磺吡酮或口服避孕药并未显著改变Sectral的动力学特性。

Drug interaction studies with tolbutamide and warfarin indicated no influence on the therapeutic effects of these compounds. Digoxin and hydrochlorothiazide plasma levels were not affected by concomitant Sectral /acebutolol hydrochloride/ administration. The kinetics of sectral were not significantly altered by concomitant administration of hydrochlorothiazide, hydralazine, sulfinpyrazone, or oral contraceptives.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

盐酸醋丁洛尔的体内分布尚未完全表征。在大鼠静脉注射后，醋丁洛尔广泛分布于许多组织，包括心脏、肝脏、肾脏、肺、肠、胃和唾液腺，但仅极少量分布于脑脊液或睾丸。在健康个体口服盐酸醋丁洛尔后，醋丁洛尔以及程度较小的二醋丁洛尔分布进入唾液，并极少量进入脑脊液。口服单次300毫克剂量的盐酸醋丁洛尔后，约3-9%的剂量在24小时内分布进入胆汁，大约相当于醋丁洛尔和二醋丁洛尔的等量。醋丁洛尔在胆汁中的峰浓度大约是血浆峰浓度的60-100倍。

Distribution of acebutolol hydrochloride into body tissue and fluids has not been fully characterized. Following IV administration in rats, acebutolol is distributed extensively into many tissues, including heart, liver, kidneys, lungs, intestines, stomach, and salivary glands, but only minimally into CSF or testes. Following oral administration of acebutolol hydrochloride in healthy individuals, acebutolol and, to a lesser extent, diacetolol, are distributed into saliva and minimally into CSF. Following oral administration of a single 300-mg dose of acebutolol hydrochloride, about 3-9% of the dose is distributed into bile within 24 hours, in approximately equivalent amounts as acebutolol and diacetolol. Peak biliary concentrations of acebutolol are approximately 60-100 times greater than peak plasma concentrations.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

乙酰布洛尔和双乙酰洛尔能轻易穿过胎盘并在胎儿体内积聚。在接受乙酰布洛尔的孕妇中，脐静脉与母体静脉血浆中乙酰布洛尔和双乙酰洛尔的平均比率分别为0.8（范围：0.5-1）和0.6（范围：0.3-0.8）。

Acebutolol and diacetolol readily cross the placenta and can accumulate in the fetus. In pregnant women receiving acebutolol, the mean acebutolol and diacetolol ratios of umbilical venous to maternal venous plasma concentrations were 0.8 (range: 0.5-1) and 0.6 (range: 0.3-0.8), respectively.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

静脉给药后，醋丁洛尔迅速广泛分布到血管外空间，健康成年人中药物的表观分布容积约为1.6-3升/千克（范围：1-3.8升/千克）。在健康个体中，静脉给药后中央室的分布容积和稳态时的平均分布容积分别为0.16-0.22升和大约1.2升/千克。老年患者的表观分布容积可能会降低。

Following IV administration, acebutolol is rapidly and widely distributed into the extravascular space and the apparent volume of distribution of the drug in healthy adults is approximately 1.6-3 l/kg (range: 1-3.8 l/kg). In healthy individuals, the volume of distribution in the central compartment and at steady state averages 0.16-0.22 and approximately 1.2 l/kg, respectively, following IV administration. The apparent volume distribution may be decreased in geriatric patients.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

体外实验中，在血浆中阿塞洛尔（acebutolol）和二乙酰洛尔（diacetolol）的蛋白结合率分别约为11-35%和6-9%，当血浆中阿塞洛尔浓度为20-9,000 ng/ml时。阿塞洛尔大约有50%与红细胞结合。

In vitro, acebutolol and diacetolol are approximately 11-35 and 6-9% bound, respectively, to plasma proteins at plasma acebutolol concentrations of 20-9,000 ng/ml. Acebutolol is approximately 50% bound to erythrocytes.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S36
• 危险类别码：
  R20/21/22
• WGK Germany：
  3
• 海关编码：
  2924296000
• RTECS号：
  ES5235000
• 储存条件：
  密封，在2至-8摄氏度下保存

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : Acebutolol hydrochloride
CAS-No. : 34381-68-5
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 [EU-GHS/CLP]
Acute toxicity, Inhalation (Category 4)
Acute toxicity, Dermal (Category 4)
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Harmful by inhalation, in contact with skin and if swallowed.
Label elements
Labelling according Regulation (EC) No 1272/2008 [CLP]
Pictogram
Signal word Warning
Hazard statement(s)
H312 Harmful in contact with skin.
H332 Harmful if inhaled.
Precautionary statement(s)
P280 Wear protective gloves/ protective clothing.
Supplemental Hazard none
Statements
According to European Directive 67/548/EEC as amended.
Hazard symbol(s)
R-phrase(s)
R20/21/22 Harmful by inhalation, in contact with skin and if swallowed.
S-phrase(s)
S36 Wear suitable protective clothing.
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Synonyms : N-(3-Acetyl-4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl)butanamide
Formula : C18H28N2O4 · HCl
Molecular Weight : 372,89 g/mol
Component Concentration
(+/-)-N-[3-Acetyl-4-[2-hydroxy-3-[(isopropyl)amino]propoxy]phenyl]butyramide monohydrochloride
CAS-No. 34381-68-5 -
EC-No. 251-980-3

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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
Nausea, Vomiting, Diarrhoea, Dizziness, Impairment of vision, Blood disorders, Rash
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
Carbon oxides, nitrogen oxides (NOx), Hydrogen chloride gas
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 vapors, mist or gas. Ensure
adequate ventilation. Avoid breathing dust.
Environmental precautions
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.
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 uses
no data available

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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
Complete suit protecting against chemicals, The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher
level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges.
Use respirators and components tested and approved under appropriate government standards
such as NIOSH (US) or CEN (EU).

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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) Evaporation 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) Autoignition 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
no data available
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
no data available
Hazardous decomposition products
Other decomposition products - no data available

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Section 11. TOXICOLOGICAL INFORMATION
Information on toxicological effects
Acute toxicity
LD50 Oral - rat - 6.620 mg/kg
Remarks: Behavioral:Change in motor activity (specific assay). Behavioral:Ataxia. Respiratory disorder
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitization
no data available
Germ cell mutagenicity
no data available
Carcinogenicity
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
Developmental Toxicity - rat - Intravenous
Specific Developmental Abnormalities: Musculoskeletal system.
Developmental Toxicity - rat - Oral
Specific Developmental Abnormalities: Musculoskeletal system. Effects on Newborn: Weaning or lactation
index (e.g., # alive at weaning per # alive at day 4). Effects on Newborn: Delayed effects.
Specific target organ toxicity - single exposure
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Potential health effects
Inhalation
Harmful if inhaled. May cause respiratory tract irritation.
Ingestion May be harmful if swallowed.
Skin Harmful if absorbed through skin. May cause skin irritation.
Eyes May cause eye irritation.
Signs and Symptoms of Exposure
Nausea, Vomiting, Diarrhoea, Dizziness, Impairment of vision, Blood disorders, Rash
Additional Information
RTECS: ES5235000

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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
no data available
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
This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006.
Safety, health and environmental regulations/legislation specific for the substance or mixture
no data available
Chemical Safety Assessment
no data available

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Section 16. OTHER INFORMATION
Further information
Copyright 2012 Co. LLC. License granted to make unlimited paper copies for internal use
only.
The above information is believed to be correct but does not purport to be all inclusive and shall be
used only as a guide. The information in this document is based on the present state of our knowledge
and is applicable to the product with regard to appropriate safety precautions. It does not represent any
guarantee of the properties of the product. Corporation and its Affiliates shall not be held
liable for any damage resulting from handling or from contact with the above product. See
and/or the reverse side of invoice or packing slip for additional terms and conditions of sale.

制备方法与用途

生物活性

Acebutolol HCl 是一种 β-肾上腺素能受体拮抗剂，用于治疗高血压、心绞痛和心律失常。

靶点

Target	Value
β-adrenergic receptor

体外研究

Acebutolol 抑制大鼠脑 P2 片段摄取 NA，其 IC50 值为 0.25 mM。与 Alprenolol 和 Oxprenolol（后者与 LDL 结合）相比，Acebutolol 对 J774 巨噬细胞中胆固醇酯的细胞内积累具有更强的抑制作用。

体内研究

• Acebutolol (10 mg/kg) 单独静脉注射给药大鼠后，血浆清除率为 61.9 mL/min/kg，分布容积为 9.6 L/kg，消除半衰期为 1.8 小时。
• Acebutolol (50 mg/kg) 单独静脉注射给药大鼠后，血浆清除率为 46.5 mL/min/kg，分布容积为 9.5 L/kg，消除半衰期为 2.3 小时。
• Acebutolol (30 mg/kg) 处理 Sprague-Dawley 大鼠，1 分钟和 10 分钟后测量的心输出量分别下降了 65% 和 31%。Acebutolol (30 mg/kg) 处理大鼠后，1 分钟或 10 分钟内大部分器官的局部血流量（RBF）显著降低。

类别

有毒物品

毒性分级

中毒

急性毒性

• 口服 - 大鼠 LD50:6620 毫克/公斤
• 口服 - 小鼠 LD50:4050 毫克/公斤

可燃性危险特性

可燃；加热分解释放有毒氮氧化物和氯化氢烟雾

储运特性

库房通风低温干燥

灭火剂

干粉、泡沫、砂土

反应信息

• 作为反应物：
  描述：

  醋丁洛尔盐酸盐 在 盐酸 作用下， 以 水 为溶剂， 反应 5.0h， 生成 外消旋N-去丁酰基醋丁洛尔
  参考文献：
  名称：

  A proposed mechanism for the adverse effects of acebutolol: CES2 and CYP2C19-mediated metabolism and antinuclear antibody production

  摘要：

  Acebutolol, a beta-adrenergic receptor-blocker, occasionally causes drug-induced lupus erythematosus (DILE). Acebutolol is mainly metabolized to diacetolol. Because metabolic activation has been considered to be related to acebutolol-induced toxicity, we sought to identify the enzymes that are responsible for acebutolol metabolism and investigate their involvement in acebutolol-induced toxicity. By using human liver microsomes (HLM) or intestinal microsomes and recombinant enzymes, we found that diacetolol was produced via hydrolysis by carboxylesterase 2 (CES2) and subsequent acetylation by N-acetyltransferase 2 (NAT2). When acetolol, a hydrolytic metabolite of acebutolol, was incubated with HLM and an NADPH-generating system, a metabolite conjugated with N-acetylcystein was generated. This metabolite was found to be formed by CYP2C19 based on studies with a panel of recombinant cytochrome P450 enzymes and an inhibition study using HLM with tranylcypromine, a CYP2C19 inhibitor. Because antinuclear antibody (ANA) production is associated with DILE, we investigated whether ANA was detected in plasma from mice treated with acebutolol. Administration of acebutolol (100 mg/kg, p.o.) to female C57BL/6 mice for 30 days resulted in ANA production in plasma in seven of thirteen mice. The number of mice that showed ANA production was larger in mice co-treated with pregnenolone 16 alpha-carbonitrile, an inducer of P450s, whereas it was lower in mice co-treated with tri-o-tolylphosphate or 1-aminobenzotriazole, which are inhibitors of esterases or P450s, respectively. These results suggested that the hydrolysis and oxidation of acebutolol was associated with ANA production. In summary, this study demonstrated that metabolic activation may be a causal factor of adverse reactions of acebutolol. (C) 2015 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2015.09.016

文献信息

• Dibenzylamine compound and medicinal use thereof
  申请人：Maeda Kimiya

  公开号：US20050059810A1

  公开（公告）日：2005-03-17

  A dibenzylamine compound represented by the formula (1) wherein R 1 and R 2 are each a C 1-6 alkyl group optionally substituted by halogen atoms and the like; R 3 , R 4 and R 5 are each a hydrogen atom, a halogen atom and the like, or R 3 and R 4 may form, together with carbon atoms bonded thereto, a homocyclic or heterocyclic ring optionally having substituent(s); A is —N(R 7 ) (R 8 ) and the like; ring B is an aryl group or a heterocyclic residue; R 6 is a hydrogen atom, a halogen atom, a nitro group, a C 1-6 alkyl group and the like; n is an integer of 1 to 3, a prodrug thereof and a pharmaceutically acceptable salt thereof show selective and potent CETP inhibitory activity, and therefore, they can be provided as therapeutic or prophylactic agents for hyperlipidemia or arteriosclerosis and the like.

  一种二苄胺化合物，其化学式如下： 其中，R1和R2分别是C1-6烷基基团，可选择性地被卤原子等取代；R3、R4和R5分别是氢原子、卤原子等，或者R3和R4可以与与之相结合的碳原子一起形成一个具有取代基的同环或异环环；A是-N(R7)(R8)等；环B是芳基或杂环残基；R6是氢原子、卤原子、硝基、C1-6烷基基团等；n是1到3的整数，其前体和药学上可接受的盐表现出选择性和强效的CETP抑制活性，因此，它们可以作为治疗或预防高脂血症或动脉硬化等疾病的药物。
• 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs
  申请人：DeAngelis Alan

  公开号：US20060058393A1

  公开（公告）日：2006-03-16

  The invention features 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs, compositions containing them, and methods of using them as PPAR modulators to treat or inhibit the progression of, for example, dyslipidemia.

  这项发明涉及4-((苯氧烷基)硫基)-苯氧乙酸及其类似物，含有它们的组合物，以及将它们用作PPAR调节剂来治疗或抑制例如脂质代谢异常的进展的方法。
• [EN] TARGETED DRUG DELIVERY THROUGH AFFINITY BASED LINKERS<br/>[FR] ADMINISTRATION CIBLÉE D'UN MÉDICAMENT FAISANT APPEL À DES COUPLEURS FONDÉS SUR L'AFFINITÉ
  申请人：INVICTUS ONCOLOGY PVT LTD

  公开号：WO2015148126A1

  公开（公告）日：2015-10-01

  The current invention discloses targeted drug delivery conjugates comprising a targeting moiety linked to a drug via a molecule having an affinity for the targeting moiety. Typically, the conjugate comprises a targeting ligand and a molecule of interest, e.g., a therapeutic agent. The targeting ligand and the molecule of interest are linked to each other via an affinity ligand. The affinity ligand is further covalently or non-covalently linked to a drug or therapeutic agent. The drug can be modified to make it more soluble and so that it cleaves from the linking molecule at the target site.

  当前的发明揭示了包括通过具有与靶向基团亲和力的分子连接到药物的靶向药物传递共轭物。通常，该共轭物包括一个靶向配体和一个感兴趣的分子，例如，一个治疗剂。靶向配体和感兴趣的分子通过一个亲和配体相互连接。该亲和配体进一步以共价或非共价方式连接到药物或治疗剂。药物可以被修改以使其更溶解，并使其在靶点处从连接分子中解离。
• Novel Bicyclic Pyridinones
  申请人：Pettersson Martin Youngjin

  公开号：US20120252758A1

  公开（公告）日：2012-10-04

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I as defined herein. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  所述化合物及其药用可接受的盐被披露，其中所述化合物具有如本文所定义的Formula I的结构。相应的药物组合物、治疗方法、合成方法和中间体也被披露。
• Nitrogen-containing fused ring compounds and use thereof
  申请人：Hirata Kazuyuki

  公开号：US20070010670A1

  公开（公告）日：2007-01-11

  A URAT1 activity inhibitor containing a nitrogen-containing fused ring compound represented by the following formula [1]: wherein each symbol is as defined in the description. The present invention is useful for the prophylaxis or treatment of pathology showing involvement of uric acid, such as hyperuricemia, gouty tophus, acute gouty arthritis, chronic gouty arthritis, gouty kidney, urolithiasis, renal function disorder, coronary artery disease, ischemic heart disease and the like.

  一种包含氮含有融合环化合物的URAT1活性抑制剂，其化学式如下所示[1]： 其中每个符号如描述中所定义。本发明对于预防或治疗显示尿酸参与的病理学，如高尿酸血症、痛风石、急性痛风性关节炎、慢性痛风性关节炎、痛风性肾脏、尿路结石、肾功能障碍、冠状动脉疾病、缺血性心脏病等方面具有用处。