尼普地洛
尼普地洛用途
β-阻断作用和血管扩张作用,无内源性拟交感作用,可降低心搏数,减少心肌耗氧量和冠脉血流量,还有抗心律不齐作用。用于轻至中度原发性高血压。
尼普地洛名称
[ CAS 号 ]:
81486-22-8
[ 中文名 ]:
尼普地洛
[ 英文名 ]:
Nipradilol
[英文别名 ]:
- nipradilol(jan)
- Nipradolol
- Nipradilol (JAN)
- Nipradilol
- Hypadil
- K-351
- Nipradilolum [Latin]
尼普地洛生物活性
[ 描述 ]:
[ 相关类别 ]:
[ 靶点 ]
α1-adrenergic receptor
[体外研究]
[体内研究]
[参考文献]
尼普地洛物理化学性质
[ 密度 ]:
1.3±0.1 g/cm3
[ 沸点 ]:
500.0±45.0 °C at 760 mmHg
[ 熔点 ]:
110-122ºC
[ 分子式 ]:
C15H22N2O6
[ 分子量 ]:
326.345
[ 闪点 ]:
256.2±28.7 °C
[ 精确质量 ]:
326.147797
[ PSA ]:
105.77000
[ LogP ]:
1.97
[ 外观性状 ]:
无色针状晶体
[ 蒸汽压 ]:
0.0±1.3 mmHg at 25°C
[ 折射率 ]:
1.561
尼普地洛毒性和生态
CHEMICAL IDENTIFICATION
- RTECS NUMBER :
- DJ2887000
- CHEMICAL NAME :
- 2H-1-Benzopyran-3-ol, 3,4-dihydro-8-(2-hydroxy-3-((1-methylethyl)amino)prop oxy)-, 3-nitrate
- CAS REGISTRY NUMBER :
- 81486-22-8
- LAST UPDATED :
- 199612
- DATA ITEMS CITED :
- 20
- MOLECULAR FORMULA :
- C15-H22-N2-O6
- MOLECULAR WEIGHT :
- 326.39
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 1040 mg/kg
- TOXIC EFFECTS :
- Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,725,1985
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intraperitoneal
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 144 mg/kg
- TOXIC EFFECTS :
- Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,725,1985
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Subcutaneous
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 850 mg/kg
- TOXIC EFFECTS :
- Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,725,1985
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 78 mg/kg
- TOXIC EFFECTS :
- Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,725,1985
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 461 mg/kg
- TOXIC EFFECTS :
- Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,725,1985
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intraperitoneal
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 147 mg/kg
- TOXIC EFFECTS :
- Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,725,1985
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Subcutaneous
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 416 mg/kg
- TOXIC EFFECTS :
- Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,725,1985
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 68 mg/kg
- TOXIC EFFECTS :
- Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,725,1985
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Mammal - dog
- DOSE/DURATION :
- >400 mg/kg
- TOXIC EFFECTS :
- Behavioral - somnolence (general depressed activity) Gastrointestinal - nausea or vomiting Lungs, Thorax, or Respiration - dyspnea
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,725,1985
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Mammal - dog
- DOSE/DURATION :
- 20 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,725,1985
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rabbit
- DOSE/DURATION :
- 300 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,725,1985
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - rabbit
- DOSE/DURATION :
- 20 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- REFERENCE :
- IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 20,228,1989 ** OTHER MULTIPLE DOSE TOXICITY DATA **
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 5250 mg/kg/5W-C
- TOXIC EFFECTS :
- Liver - changes in liver weight Endocrine - changes in spleen weight Nutritional and Gross Metabolic - weight loss or decreased weight gain
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,733,1985
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 93600 mg/kg/52W-I
- TOXIC EFFECTS :
- Kidney, Ureter, Bladder - other changes in urine composition Blood - normocytic anemia Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 30,221,1985 ** REPRODUCTIVE DATA **
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 5400 mg/kg
- SEX/DURATION :
- female 17-22 day(s) after conception lactating female 21 day(s) post-birth
- TOXIC EFFECTS :
- Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4)
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 30,1,1985
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 4400 mg/kg
- SEX/DURATION :
- female 7-17 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Newborn - live birth index (measured after birth)
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,747,1985
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 2200 mg/kg
- SEX/DURATION :
- female 7-17 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Effects on Embryo or Fetus - fetal death
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,747,1985
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 550 mg/kg
- SEX/DURATION :
- female 7-17 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Specific Developmental Abnormalities - musculoskeletal system
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,747,1985
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 2700 mg/kg
- SEX/DURATION :
- female 17-22 day(s) after conception lactating female 21 day(s) post-birth
- TOXIC EFFECTS :
- Reproductive - Effects on Newborn - physical
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 30,1,1985
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 260 mg/kg
- SEX/DURATION :
- female 6-18 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Embryo or Fetus - fetal death
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,747,1985
尼普地洛合成路线
尼普地洛上下游产品
尼普地洛上游产品
尼普地洛下游产品
尼普地洛制备
消旋体的制备。1.82g2-烯丙基-6-甲氧基苯基乙酸酯溶于20ml二氯甲烷,加入3.0ml40%(W/V)过氧乙酸溶液和0.18g乙酸钾,在室温下搅拌48h。将反应液加到100ml氯仿和50ml5%亚硫酸钠水溶液中。分出有机层,水洗,无水硫酸钠干燥。减压浓缩得1.74g淡黄色粘稠液体的化合物(Ⅰ),收率88.7%。
1.74g化合物(Ⅰ)溶于10ml乙醚,在0℃加入5.0ml20%(W/V)氯化氢的乙醚溶液,在室温下搅拌12h。加入100ml乙醚,用饱和碳酸氢钠溶液中和。分出醚层,水洗,无水硫酸钠干燥。减压浓缩得1.83g淡黄色粘稠液体的化合物(Ⅱ),收率90.4%。
1.82g化合物(Ⅱ)溶于10ml二甲基甲酰胺,加入1.26g碳酸钾,在室温下搅拌2h后,加入50ml水和100ml苯。分出有机层,水洗,无水硫酸钠干燥。减压浓缩得1.53g淡黄色粘稠液体的化合物(Ⅲ)。
1.53g化合物(Ⅲ)溶于30ml甲醇,加入10ml1mol/L氢氧化钠溶液。在室温下搅拌1h后,加入12ml1mol/L盐酸。减压浓缩,剩余物用30ml苯提取。提取液水洗,无水硫酸钠干燥。减压浓缩得到的棕色粘稠油用苯-己烷重结晶,得0.66g无色棱状结晶的化合物c,收率52.1%,熔点79~82℃。
1.50g化合物1mol/L加到8.60g47%氢溴酸中,在90℃下搅拌9h。冷至室温,用氢氧化钠水溶液调至弱酸性后,用30ml乙酸乙酯提取。提取液用饱和盐水洗,无水硫酸钠干燥。减压浓缩,丙酮结晶得棕色固体。再用乙酮和己烷重结晶,得1.23g无色针状结晶的化合物(Ⅴ),收率88.9%,熔点126~129℃。
20mmol化合物(Ⅴ)和23mmol三乙胺溶于20ml四氢呋喃,在0~5℃加入23mmol氯甲酸乙酯(或三氯乙酰氯)溶于35ml四氢呋喃的溶液,再搅拌0.5h。过滤,滤液减压浓缩。剩余物(4.85g)溶于80ml乙腈,冷至-8~-10℃,加入乙酰硝酸酯(从2.22g乙酸酐和1.36g发烟硝酸制得),在此温度再搅拌0.5h。再在-8℃加入另一份乙酰硝酸酯(从1.36g乙酸酐和0.85g发烟硝酸制得),继续搅拌0.5h。加入碳酸氢钠以终止反应,用180ml乙酸乙酯提取。提取液用碳酸氢钠溶液和饱和盐水洗,干燥,浓缩至干。剩余物棕色油溶于10ml甲醇和0.93g氢氧化钠溶于5ml水的混合溶液,在室温下搅拌0.5h。用浓盐酸酸化后,减压蒸去甲醇,用60ml乙酸乙酯提取。提取液用饱和盐水洗,干燥,浓缩至干。剩余的深棕色油用硅胶柱层析,用苯洗脱。得到的固体再用苯和己烷结晶,得无色结晶的化合物(Ⅵ),收率65%,熔点101~103℃。
4mmol化合物(Ⅵ)溶于15ml1mol/L氢氧化钠,加入16mmol环氧氯丙烷,在50℃下搅拌2h。加入30ml乙酸乙酯。分出有机层,用10ml1mol/L氢氧化钠溶液和10ml饱和盐水洗,干燥,浓缩至干。得到的油状物无需提纯,可直接用于下列反应。取4mmol该油溶于30ml甲醇,加入20mmol异丙胺,在70℃下加热1h。浓缩至干,剩余油状物用三氧化二铝柱层析,氯仿洗脱。得到的固体用乙酸乙酯和己烷结晶,得尼普地洛,收率61%,熔点110~122℃。
推荐生产厂家/供应商:
相关化合物
【尼普地洛】化源网提供尼普地洛CAS号81486-22-8,尼普地洛MSDS及其说明、性质、英文名、生产厂家、作用/用途、分子量、密度、沸点、熔点、结构式等。CAS号查询尼普地洛上化源网,专业又轻松。>>电脑版:尼普地洛
标题:尼普地洛_用途_密度_熔点_尼普地洛CAS号【81486-22-8】_化源网 地址:https://m.chemsrc.com/mip/cas/81486-22-8_81269.html