959-24-0

• 常用中文名：盐酸索他洛尔
• 常用英文名：Sotalol hydrochloride
• CAS号：959-24-0
• 分子式：C₁₂H₂₁ClN₂O₃S
• 分子量：308.825
• 相关类别： 原料药 循环系统用药 抗心律失常药
• 发布时间：2018-08-19 09:23:15
• 更新时间：2024-01-04 09:30:38
• Sotalol盐酸盐是肾上腺素受体拮抗剂,可作用于威胁生命的心律失常。

名称

• 中文名: 盐酸索他洛尔
• 英文名: sotalol hydrochloride
• 中文别名: N-[4-[1-羟基-2-(异丙基氨基)乙基]苯基]甲盐酸; 4'-(1-羟基-2-异丙胺乙基)甲磺酸苯胺盐酸盐
• 英文别名: MFCD00242937; Sotacor; Sotalol hydrochloride; Betapace; (±)-Sotalol hydrochloride; N-(4-{1-Hydroxy-2-[(1-methylethyl)amino]ethyl}phenyl)methansulfonamidhydrochlorid; EINECS 213-496-0; N-Isopropyl-b-(4-methanesulfonamidophenyl)ethanolamine Hydrochloride; Methanesulfonamide, N-[4-[1-hydroxy-2-[(1-methylethyl)amino]ethyl]phenyl]-, hydrochloride (1:1); methanesulfonamide, N-[4-[1-hydroxy-2-[(1-methylethyl)amino]ethyl]phenyl]-, monohydrochloride; N-Isopropyl-β-(4-methanesulfonamidophenyl)ethanolamine hydrochloride; 4'-[1-Hydroxy-2-(isopropylamino)ethyl]methanesulfonanilide monohydrochloride; b-Cardone; N-{4-[1-Hydroxy-2-(isopropylamino)ethyl]phenyl}methanesulfonamide hydrochloride (1:1); β-Cardone; N-{4-[1-hydroxy-2-(propan-2-ylamino)ethyl]phenyl}methanesulfonamide hydrochloride (1:1); N-(4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)phenyl)methanesulfonamide Monohydrochloride; Sotalol Monohydrochloride; 4'-[1-Hydroxy-2-(isopropylamino)ethyl]methanesulfonanilide hydrochloride; N-(4-{1-hydroxy-2-[(1-méthyléthyl)amino]éthyl}phényl)méthanesulfonamide chlorhydrate; Sotalol (hydrochloride)

物化性质

• 沸点: 443.3ºC at 760 mmHg
• 熔点: 218-220°C
• 分子式: C₁₂H₂₁ClN₂O₃S
• 分子量: 308.825
• 闪点: 221.9ºC
• 精确质量: 308.096130
• PSA: 86.81000
• LogP: 3.43620
• 外观性状: 白色至灰白色粉末
• 储存条件:

  保持容器密封，储存在阴凉，干燥的地方

• 稳定性:

  常温常压下稳定，避免氧化物接触

• 水溶解性: H2O: 20 mg/mL
• 计算化学:

  1.疏水参数计算参考值（XlogP）:无

  2.氢键供体数量:4

  3.氢键受体数量:5

  4.可旋转化学键数量:6

  5.互变异构体数量:无

  6.拓扑分子极性表面积86.8

  7.重原子数量:19

  8.表面电荷:0

  9.复杂度:330

  10.同位素原子数量:0

  11.确定原子立构中心数量:0

  12.不确定原子立构中心数量:1

  13.确定化学键立构中心数量:0

  14.不确定化学键立构中心数量:0

  15.共价键单元数量:2

• 更多:

  1. 性状：白色或类白色粉末

  2. 密度（g/mL,25/4℃）：未确定

  3. 相对蒸汽密度（g/mL,空气=1）：未确定

  4. 熔点（ºC）：218-220°C

  5. 沸点（ºC,常压）：未确定

  6. 沸点（ºC,5.2kPa）：未确定

  7. 折射率：未确定

  8. 闪点（ºC）：未确定

  9. 比旋光度（º）：未确定

  10. 自燃点或引燃温度（ºC）：未确定

  11. 蒸气压（kPa,25ºC）：未确定

  12. 饱和蒸气压（kPa,60ºC）：未确定

  13. 燃烧热（KJ/mol）：未确定

  14. 临界温度（ºC）：未确定

  15. 临界压力（KPa）：未确定

  16. 油水（辛醇/水）分配系数的对数值：未确定

  17. 爆炸上限（%,V/V）：未确定

  18. 爆炸下限（%,V/V）：未确定

  19. 溶解性：H₂O: 20mg/mL

生物活性

• 描述: Sotalol盐酸盐是肾上腺素受体拮抗剂,可作用于威胁生命的心律失常。
• 相关类别:
  信号通路 >> G 蛋白偶联受体/G 蛋白 >> 肾上腺素能受体
  研究领域 >> 心血管疾病
• 参考文献:

  [1]. Antonaccio, M.J. and A. Gomoll, Pharmacologic basis of the antiarrhythmic and hemodynamic effects of sotalol. Am J Cardiol, 1993. 72(4): p. 27A-37A.

  [2]. Bertrix, L., et al., Protection against ventricular and atrial fibrillation by sotalol. Cardiovasc Res, 1986. 20(5): p. 358-63.

毒性和生态

毒理学数据: 1、急性毒性：小鼠口经LD50：2600mg/kg；大鼠口经LD50：3450mg/kg 2、急性毒性：小鼠腹腔LD50：670mg/kg；大鼠腹腔LD50：680mg/kg 生态学数据: 对水是稍微有害的，不要让未稀释或大量的产品接触地下水，水道或者污水系统，若无政府许可，勿将材料排入周围环境 CHEMICAL IDENTIFICATION RTECS NUMBER : PB0826000 CHEMICAL NAME : Methanesulfonanilide, 4'-(1-hydroxy-2-(isopropylamino)ethyl)-, monohydrochloride CAS REGISTRY NUMBER : 959-24-0 LAST UPDATED : 199609 DATA ITEMS CITED : 16 MOLECULAR FORMULA : C12-H20-N2-O3-S.Cl-H MOLECULAR WEIGHT : 308.86 WISWESSER LINE NOTATION : WS1&MR DYQ1MY1&1 &GH HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 45714 ug/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Behavioral - excitement Lungs, Thorax, or Respiration - dyspnea REFERENCE : ARTODN Archives of Toxicology. (Springer-Verlag, Heidelberger Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.32- 1974- Volume(issue)/page/year: 43,221,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 64 mg/kg/2W-I TOXIC EFFECTS : Cardiac - arrhythmias (including changes in conduction) REFERENCE : BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 291,544,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 3450 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity) Behavioral - ataxia REFERENCE : JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 149,161,1965 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 680 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay) Behavioral - ataxia REFERENCE : JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 149,161,1965 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 2600 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay) Behavioral - ataxia REFERENCE : JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 149,161,1965 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 670 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay) Behavioral - ataxia REFERENCE : JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 149,161,1965 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 330 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation Behavioral - changes in motor activity (specific assay) Behavioral - ataxia REFERENCE : JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 149,161,1965 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 1 gm/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay) Behavioral - ataxia REFERENCE : JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 149,161,1965 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 69450 mg/kg/30D-I TOXIC EFFECTS : Liver - changes in liver weight Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23,2895,1995 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 281 gm/kg/1Y-I TOXIC EFFECTS : Cardiac - changes in heart weight Kidney, Ureter, Bladder - urine volume increased Endocrine - changes in spleen weight REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23,2913,1995 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 126 gm/kg SEX/DURATION : male 9 week(s) pre-mating female 2 week(s) pre-mating - 7 day(s) after conception TOXIC EFFECTS : Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23,1995,1995 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 280 mg/kg SEX/DURATION : female 8-21 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - behavioral REFERENCE : EJPHAZ European Journal of Pharmacology. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1967- Volume(issue)/page/year: 195,75,1991 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 8085 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23,2007,1995 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 24960 mg/kg SEX/DURATION : female 17-21 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Maternal Effects - other effects Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23,2031,1995 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 2340 mg/kg SEX/DURATION : female 6-18 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23,2023,1995 *** REVIEWS *** TOXICOLOGY REVIEW FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 6,395,1986

安全

• 符号: GHS07
• 信号词: Warning
• 危害声明: H315-H319-H335
• 警示性声明: P261-P305 + P351 + P338
• 个人防护装备: dust mask type N95 (US);Eyeshields;Gloves
• 危害码 (欧洲): Xi:Irritant;
• 风险声明 (欧洲): R36/37/38
• 安全声明 (欧洲): S26-S36
• 危险品运输编码: NONH for all modes of transport
• WGK德国: 3
• RTECS号: PB0826000
• 海关编码: 2942000000

制备

1. 甲磺酰苯胺的制备

在反应瓶中加入苯胺15.5g(0.16mol)、三乙胺12ml和乙醇150ml冰盐浴冷却下搅拌滴加甲烷磺酰氯20g(0.17mol),控制滴加速度以保持内温在-5~0ºC之间为准,滴加毕,于室温搅拌反应4h.过滤#滤液浓缩至原体积的1/2,冷却至0ºC下析晶,过滤,用乙醇重结晶,干燥,得白色晶体甲磺酰苯胺23g,收率84%,mp>293ºC.Rf0.7[展开剂:氯仿/甲醇(3:1)]

2. 4’-(2-溴乙酰基)甲磺酰苯胺的制备

在反应瓶中加入上步制备的化合物甲磺酰苯胺8.55g(0.055mol)、溴乙酰溴15g(0.07mol)和二硫化碳70ml,于冰水浴冷却下搅拌加入无水AlCl3 17g,控制内温在15ºC以下,加毕,于室温搅拌反应2h.搅拌回流反应1h. 蒸除溶剂,将剩余浓缩液倾入冰水中,析出固体,过滤,得粗品4’-(2-溴乙酰基)甲磺酰苯胺,为浅红色颗粒状结晶,将其用乙醇重结晶,得白色晶体,干燥后得4’-(2-溴乙酰基)甲磺酰苯胺14.1g,收率96.6%,mp191~192ºC(分解).

3. 4’-(2-异丙氨基乙酰基)甲磺酰苯胺盐酸盐的制备

在反应瓶中加入异丙胺10.0g(0.17mol)和甲醇30ml,搅拌和冰盐浴冷却下,于-5ºC左右加入4’-(2-溴乙酰基) 甲磺酰苯胺4’-(2-溴乙酰基)甲磺酰苯胺14.6g(0.05mol),继续在同温度下搅拌反应2h.将反应液减压蒸除溶剂,剩余物加入丙酮200ml,通入氯化氢气体至pH=2,冷却,过滤,结晶用无水乙醇重结晶#得白色晶体4’-(2-异丙氨基乙酰基)甲磺酰苯胺盐酸盐13.6g,收率65%,mp223~225ºC.

4. N-[4-[1-羟基-2-[(1-甲基乙基)氨基]乙基]苯基]甲磺酰胺盐酸盐(盐酸索他洛尔)的合成

在氢化反应瓶中加入上步制备的化合物4’-(2-异丙氨基乙酰基)甲磺酰苯胺盐酸盐19.01g(0.65mol)、甲醇200ml和10%Pd/C1.14g.用N2置换瓶中空气3次,用氢气置换N2 2次,于室温下搅拌通H2反应至不吸氢为止(常压下反应),过滤,滤液浓缩至干,得粗品,将粗品加甲醇200ml加热至全溶,加适量活性炭脱色15min.抽滤,冷却析晶,过滤,得白色晶体17g,mp206.5~207ºC,收率85%[Pd/C回收:将Pd/C置于稀盐酸中回流,再通氢气活化数小时即可]

海关

海关编码	2935009090
中文概述	2935009090 其他磺（酰）胺. 增值税率:17.0% 退税率:9.0% 监管条件:无 最惠国关税:6.5% 普通关税:35.0%
申报要素	品名, 成分含量, 用途
Summary	2935009090 other sulphonamides VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:35.0%