3737-09-5

• 常用中文名：丙吡胺
• 常用英文名：Disopyramide
• CAS号：3737-09-5
• 分子式：C₂₁H₂₉N₃O
• 分子量：339.47400
• 相关类别： 原料药 循环系统用药 抗心律失常药
• 发布时间：2018-10-01 17:03:15
• 更新时间：2024-01-03 10:05:28

• 心脏病类药。抗心律失常，适用于室上性室心早搏、各类心动过速房颤等。

名称

• 中文名: 达舒平
• 英文名: disopyramide
• 中文别名: 双异丙吡胺
• 英文别名: DISOPYRAMIDE; EINECS 223-110-2; MFCD00057366

物化性质

• 密度: 1.059g/cm3
• 沸点: 505.2ºC at 760mmHg
• 熔点: 94.5-950C
• 分子式: C₂₁H₂₉N₃O
• 分子量: 339.47400
• 闪点: 259.4ºC
• 精确质量: 339.23100
• PSA: 59.22000
• LogP: 4.06220
• 储存条件: 2-8°C
• 分子结构:

  1、摩尔折射率：102.12

  2、摩尔体积（cm³/mol）：320.2

  3、等张比容（90.2K）：816.9

  4、表面张力（dyne/cm）：42.3

  5、介电常数：无可用的

  6、极化率（10^-24cm³）：40.48

  7、单一同位素质量：339.231063Da

  8、标称质量：339Da

  9、平均质量：339.4745Da

• 计算化学:

  1、 疏水参数计算参考值（XlogP）：3.2

  2、 氢键供体数量：1

  3、 氢键受体数量：3

  4、 可旋转化学键数量：8

  5、 互变异构体数量：2

  6、 拓扑分子极性表面积（TPSA）：59.2

  7、 重原子数量：25

  8、 表面电荷：0

  9、 复杂度：409

  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：1

生物活性

• 描述: Disopyramide (Dicorantil) 是一种治疗室性和房性心律失常的 IA 类抗心律失常药物。Disopyramide 阻断心肌快速内向钠电流 (sodium current),延长心肌动作电位持续时间。Disopyramide 抑制 HERG 编码的钾通道 (potassium channels)。Disopyramide 也表现出复杂的蛋白质结合,并具有强大的负性肌力作用。
• 相关类别:
  信号通路 >> 跨膜转运 >> 钠通道
  研究领域 >> 心血管疾病
  信号通路 >> 跨膜转运 >> 钾通道
• 体外研究: 在临床范围内(IC50=7.23μM)二锥体胺的浓度以剂量依赖的方式抑制在-40 mV和+30 mV试验脉冲后记录的HERG尾电流[1]。
• 参考文献:

  [1]. S V Jones, et al. Non-competitive Effects of Disopyramide at the Neuromuscular Junction: Evidence for Endplate Ion Channel Block. Br J Anaesth. 1987 Jun;59(6):776-83.

  [2]. L A Siddoway, et al. Clinical Pharmacokinetics of Disopyramide. Clin Pharmacokinet. May-Jun 1986;11(3):214-22.

  [3]. A A Paul, et al. Inhibition of HERG Potassium Channel Current by the Class 1a Antiarrhythmic Agent Disopyramide. Biochem Biophys Res Commun. 2001 Feb 9;280(5):1243-50.

毒性和生态

生态学数据: 通常对水是不危害的，若无政府许可，勿将材料排入周围环境。 CHEMICAL IDENTIFICATION RTECS NUMBER : UR8432000 CHEMICAL NAME : 2-Pyridineacetamide, alpha-(2-(diisopropylamino)ethyl)-alpha-phenyl- CAS REGISTRY NUMBER : 3737-09-5 LAST UPDATED : 199806 DATA ITEMS CITED : 25 MOLECULAR FORMULA : C21-H29-N3-O MOLECULAR WEIGHT : 339.53 WISWESSER LINE NOTATION : T6NJ BXR&VZ2NY1&1&Y1&1 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 4286 ug/kg TOXIC EFFECTS : Cardiac - other changes Lungs, Thorax, or Respiration - dyspnea Lungs, Thorax, or Respiration - other changes REFERENCE : NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year: 302,614,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Human - woman DOSE/DURATION : 700 mg/kg/13W-I TOXIC EFFECTS : Behavioral - coma Endocrine - hypoglycemia REFERENCE : AMDIBO Annales de Medecine Interne. (Masson Abonnements, B.P.22, F-41354 Vineuil Cedex, France) V.120- 1969- Volume(issue)/page/year: 146,209,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 333 mg/kg TOXIC EFFECTS : Behavioral - changes in motor activity (specific assay) Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory depression REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 38,1398,1988 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 170 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,319,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 800 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: 9,829,1978 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 39100 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : FRPPAO Farmaco, Edizione Pratica. (Casella Postale 227, 27100 Pavia, Italy) V.8-43 1953-88 For publisher information, see FRMCE8 Volume(issue)/page/year: 35,49,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 352 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : FRPPAO Farmaco, Edizione Pratica. (Casella Postale 227, 27100 Pavia, Italy) V.8-43 1953-88 For publisher information, see FRMCE8 Volume(issue)/page/year: 35,49,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 114 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Blood - changes in spleen REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 5,1628,1971 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 305 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,319,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 26 mg/kg TOXIC EFFECTS : Behavioral - tremor Behavioral - rigidity (including catalepsy) Lungs, Thorax, or Respiration - respiratory depression REFERENCE : USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #4237139 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 36 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - rigidity (including catalepsy) Lungs, Thorax, or Respiration - respiratory depression 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: 136,114,1962 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 42200 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : FRPPAO Farmaco, Edizione Pratica. (Casella Postale 227, 27100 Pavia, Italy) V.8-43 1953-88 For publisher information, see FRMCE8 Volume(issue)/page/year: 35,49,1980 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 24900 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : FRPPAO Farmaco, Edizione Pratica. (Casella Postale 227, 27100 Pavia, Italy) V.8-43 1953-88 For publisher information, see FRMCE8 Volume(issue)/page/year: 35,49,1980 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 14 gm/kg/35D-I TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Cardiac - arrhythmias (including changes in conduction) 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: 13,2555,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 11200 mg/kg/4W-C TOXIC EFFECTS : Blood - changes in cell count (unspecified) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases Related to Chronic Data - changes in uterine weight REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 5,1628,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 27300 mg/kg/26W-C TOXIC EFFECTS : Liver - changes in liver weight Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 5,1628,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 18200 mg/kg/13W-I TOXIC EFFECTS : Liver - fatty liver degeneration Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Related to Chronic Data - death REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 27,3536,1993 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 22260 mg/kg/53W-I TOXIC EFFECTS : Cardiac - change in rate Gastrointestinal - nausea or vomiting 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: 13,2609,1985 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 24 mg/kg SEX/DURATION : female 40-41 week(s) after conception TOXIC EFFECTS : Reproductive - Maternal Effects - parturition REFERENCE : AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920- Volume(issue)/page/year: 162,482,1990 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 11200 mg/kg SEX/DURATION : male 28 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 5,1628,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 11200 mg/kg SEX/DURATION : female 28 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Maternal Effects - uterus, cervix, vagina REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 5,1628,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 420 mg/kg SEX/DURATION : female 9-15 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 5,1641,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 1260 mg/kg SEX/DURATION : female 9-15 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 5,1641,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 1260 mg/kg SEX/DURATION : female 7-13 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 5,1641,1971 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4710 No. of Facilities: 22 (estimated) No. of Industries: 1 No. of Occupations: 3 No. of Employees: 424 (estimated) No. of Female Employees: 318 (estimated)

安全

• 符号: GHS07, GHS08
• 信号词: Warning
• 危害声明: H302-H361
• 警示性声明: P280-P301 + P312 + P330
• 危害码 (欧洲): Xn: Harmful;
• 风险声明 (欧洲): 22
• 安全声明 (欧洲): S36
• 危险品运输编码: NONH for all modes of transport
• WGK德国: 3
• RTECS号: UR8432000

制备

2-溴吡啶与苄腈、N,N-二异丙基氯乙胺缩合、水解，再与磷酸成盐即得到治疗心律失常药双异丙吡胺。