64241-34-5

• 常用中文名：2-(6-(乙基(2-羟丙基)氨基)哒嗪-3-基)肼甲酸乙酯
• 常用英文名：Cadralazine
• CAS号：64241-34-5
• 分子式：C₁₂H₂₁N₅O₃
• 分子量：283.32700
• 相关类别： 原料药 循环系统用药 抗高血压病药
• 发布时间：2018-04-25 08:00:00
• 更新时间：2024-01-14 13:04:28
• 卡达拉嗪(ISF 2469)是一种口服活性抗高血压药物。卡达拉嗪是一种外周动脉血管扩张剂[1]。

名称

• 中文名: 卡屈嗪
• 英文名: ethyl N-[[6-[ethyl(2-hydroxypropyl)amino]pyridazin-3-yl]amino]carbamate
• 中文别名: 2-[6-[乙基(2-羟丙基)氨基]-3-哒嗪基]肼羧酸乙酯; 卡柔比星
• 英文别名: DC-826; Cadralazine [INN:BAN:JAN]; 2-[6-[Ethyl(2-Hydroxypropyl)Amino]-3-Pyridazinyl]-Hydrazinecarboxylic Acid Ethyl Ester; Cadralazina [INN-Spanish]; ISF 2469; Cadralazine; Cadralazina [Spanish]; Cadralazinum [INN-Latin]; N'-{6-[ethyl-(2-hydroxy-propyl)-amino]-pyridazin-3-yl}-hydrazinecarboxylic acid ethyl ester

物化性质

• 密度: 1.253 g/cm3
• 沸点: 425.88°C (rough estimate)
• 熔点: 160-162°
• 分子式: C₁₂H₂₁N₅O₃
• 分子量: 283.32700
• 精确质量: 283.16400
• PSA: 99.61000
• LogP: 1.22060
• 折射率: 1.59
• 储存条件: 库房通风低温干燥
• 分子结构:

  1、 摩尔折射率：76.38

  2、 摩尔体积（cm³/mol）：226.0

  3、 等张比容（90.2K）：622.2

  4、 表面张力（dyne/cm）：57.4

  5、 极化率（10-24cm3）：30.28

• 计算化学:

  1.疏水参数计算参考值（XlogP）:1

  2.氢键供体数量:3

  3.氢键受体数量:7

  4.可旋转化学键数量:8

  5.互变异构体数量:6

  6.拓扑分子极性表面积99.6

  7.重原子数量:20

  8.表面电荷:0

  9.复杂度:292

  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

• 更多:

  1.性状：在丙酮中结晶。

  2.熔点（ºC）：160～162。

  3.pKa ：6.0。

  4.UV最大吸收：248，340m(ε22100，2250)。

  5.溶解度：溶解度(mg/m1)：水1.3，盐酸235.0，二甲亚砜323.0，甲醇21.0，二氧六环18.6，氯仿8.5，乙醚、苯及环己烷＜0.1。

生物活性

• 描述: 卡达拉嗪(ISF 2469)是一种口服活性抗高血压药物。卡达拉嗪是一种外周动脉血管扩张剂[1]。
• 相关类别:
  研究领域 >> 心血管疾病
  信号通路 >> 其他 >> 其他
• 参考文献:

  [1]. K Takeyama, et al. Antihypertensive activity of cadralazine in experimental hypertensive rats. Arch Int Pharmacodyn Ther. Jan-Feb 1988;291:163-74.

毒性和生态

毒理学数据: 急性毒性LD50大鼠，狗(mg/kg)：269，约400静脉注射；2060，＞2000口服。急性毒性LD50鼠(mg/kg)：700腹腔注射。 CHEMICAL IDENTIFICATION RTECS NUMBER : MV1720400 CHEMICAL NAME : Hydrazinecarboxylic acid, 2-(6-(ethyl(2-hydroxypropyl)amino)-3-pyridazinyl)-, ethyl ester CAS REGISTRY NUMBER : 64241-34-5 BEILSTEIN REFERENCE NO. : 0894631 LAST UPDATED : 199612 DATA ITEMS CITED : 15 MOLECULAR FORMULA : C12-H21-N5-O3 MOLECULAR WEIGHT : 283.38 WISWESSER LINE NOTATION : T6NNJ CN2&1YQ1 FMMVO2 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 : 2060 mg/kg TOXIC EFFECTS : Cardiac - change in rate Vascular - BP lowering not characterized in autonomic section REFERENCE : JCPCDT Journal of Cardiovascular Pharmacology. (Raven Press, 1140 Ave. of the Americas, New York, NY 10036) V.1- 1979- Volume(issue)/page/year: 3,455,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 440 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 7,382,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - altered sleep time (including change in righting reflex) Liver - other changes 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: 15,3839,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 269 mg/kg TOXIC EFFECTS : Cardiac - change in rate Vascular - BP lowering not characterized in autonomic section REFERENCE : JCPCDT Journal of Cardiovascular Pharmacology. (Raven Press, 1140 Ave. of the Americas, New York, NY 10036) V.1- 1979- Volume(issue)/page/year: 3,455,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 825 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 7,382,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 362 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 7,382,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1420 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - altered sleep time (including change in righting reflex) Lungs, Thorax, or Respiration - dyspnea 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: 15,3839,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 162 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 7,382,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 7,382,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 400 mg/kg TOXIC EFFECTS : Cardiac - change in rate Vascular - BP lowering not characterized in autonomic section Kidney, Ureter, Bladder - changes in blood vessels or in circulation of kidney REFERENCE : JCPCDT Journal of Cardiovascular Pharmacology. (Raven Press, 1140 Ave. of the Americas, New York, NY 10036) V.1- 1979- Volume(issue)/page/year: 3,455,1981 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 36400 mg/kg/52W-C TOXIC EFFECTS : Kidney, Ureter, Bladder - other changes in urine composition Endocrine - changes in spleen weight Blood - changes in leukocyte (WBC) count 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: 15,3875,1987 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 9 gm/kg/30D-C TOXIC EFFECTS : Liver - changes in liver weight Endocrine - changes in spleen weight Blood - normocytic anemia 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: 15,3847,1987 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 132 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) 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: 15,3913,1987 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 3300 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system 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: 15,3913,1987 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 910 mg/kg SEX/DURATION : female 17-21 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - physical 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: 15,3945,1987

合成路线

141-30-0 40171-86-6 4114-31-2 ~% 64241-34-5

文献：US4757142 A1, ;

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制备

在约70℃时，6h内往1L N-乙基-2-羟基丙胺中，加入583g 3，6-二氯酞嗪，在95℃下搅拌16h。然后加入1.5 L水、470ml 37%盐酸和884ml肼基甲酸乙酯，回流20h。用液氨调反应液的Ph值为8.5，得776g卡屈嗪。