53179-11-6

• 常用中文名：洛哌丁胺
• 常用英文名：Loperamide
• CAS号：53179-11-6
• 分子式：C₂₉H₃₃ClN₂O₂
• 分子量：477.04
• 相关类别： 原料药 消化系统用药 泻药止泻药
• 发布时间：2018-02-23 08:00:00
• 更新时间：2024-01-04 08:10:51
• Loperamide (ADL 2-1294) 是一种选择性 μ opioid receptor 激动剂,对 μ、δ 和 κ opioid 受体的 Ki 分别为 3、48 和 1156 nM。Loperamide 可作为止泻剂。

名称

• 中文名: 洛哌丁胺
• 英文名: loperamide
• 中文别名: 4-对氯苯-4-羟基-N,N-二甲基-α,α-二苯-1-对哌啶基丁酰胺; 4-[4-(4-氯苯基)-4-羟基哌啶-1-基]-N,N-二甲基-2,2-二苯基丁酰胺; 4-(4-氯苯基)-4-羟基-N,N-二甲基-Α,Α-二苯基-1-哌啶丁酰胺; 氯苯哌丁胺
• 英文别名: Loperamida; 4-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-N,N-dimethyl-2,2-diphenylbutanamide; Maalox Anti-Diarrheal; [3H]-Loperamide; Ioperamide; Loperacap; 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-N,N-dimethyl-2,2-diphenylbutanamide; Apo-Loperamide; Kaopectate II; MFCD00600388; Imodium; Loperamidum; EINECS 258-416-5; Nu-Loperamide

物化性质

• 密度: 1.187g/cm3
• 沸点: 647.2ºC at 760 mmHg
• 分子式: C₂₉H₃₃ClN₂O₂
• 分子量: 477.04
• 闪点: 345.2ºC
• 精确质量: 476.22300
• PSA: 43.78000
• LogP: 5.02590
• 折射率: 1.6
• 分子结构:

  1、 摩尔折射率：137.52

  2、 摩尔体积（cm³/mol）：401.6

  3、 等张比容（90.2K）：1067.1

  4、 表面张力（dyne/cm）：49.8

  5、 极化率（10-24cm3）：54.51

• 计算化学:

  1.疏水参数计算参考值（XlogP）:5

  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:7

  5.互变异构体数量:无

  6.拓扑分子极性表面积43.8

  7.重原子数量:34

  8.表面电荷:0

  9.复杂度:623

  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:0

  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：从异丙醇结晶

  2.熔点：222~223

生物活性

• 描述: Loperamide (ADL 2-1294) 是一种选择性 μ opioid receptor 激动剂,对 μ、δ 和 κ opioid 受体的 Ki 分别为 3、48 和 1156 nM。Loperamide 可作为止泻剂。
• 相关类别:
  信号通路 >> G 蛋白偶联受体/G 蛋白 >> 阿片受体
  信号通路 >> 其他 >> 其他
  研究领域 >> 炎症/免疫
  信号通路 >> 神经信号通路 >> 阿片受体
• 靶点:

  Ki: 3 nM (μ opioid receptor), 48 nM (δ opioid receptor), 1156 nM (κ opioid receptor)[1]

• 参考文献:

  [1]. DeHaven-Hudkins DL, et al. Loperamide (ADL 2-1294), an opioid antihyperalgesic agent with peripheral selectivity. J Pharmacol Exp Ther. 1999 Apr;289(1):494-502.

毒性和生态

毒理学数据: 急性毒性。小鼠(mg/kg)：75皮下注射；105口服。急性毒性LD50大鼠(mg/kg)：185口服。 CHEMICAL IDENTIFICATION RTECS NUMBER : TM4959000 CHEMICAL NAME : 1-Piperidinebutanamide, 4-(4-chlorophenyl)-4-hydroxy-N,N-dimethyl-alpha,alpha -diphenyl- CAS REGISTRY NUMBER : 53179-11-6 BEILSTEIN REFERENCE NO. : 1558273 LAST UPDATED : 199612 DATA ITEMS CITED : 8 MOLECULAR FORMULA : C29-H33-Cl-N2-O2 MOLECULAR WEIGHT : 477.09 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 : 98 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : DDREDK Drug Development Research. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1981- Volume(issue)/page/year: 8,279,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 5100 ug/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor Nutritional and Gross Metabolic - body temperature increase REFERENCE : PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 3,461,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 105 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor Nutritional and Gross Metabolic - body temperature increase REFERENCE : PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 3,461,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 28 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor Nutritional and Gross Metabolic - body temperature increase REFERENCE : PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 3,461,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 75 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor Nutritional and Gross Metabolic - body temperature increase REFERENCE : PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 3,461,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 40 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor Nutritional and Gross Metabolic - body temperature increase REFERENCE : PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 3,461,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 2800 ug/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor Nutritional and Gross Metabolic - body temperature increase REFERENCE : PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 3,461,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 42 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor Nutritional and Gross Metabolic - body temperature increase REFERENCE : PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 3,461,1981

安全

• 危害码 (欧洲): C,Xi
• 风险声明 (欧洲): R34:Causes burns. R36/37/38:Irritating to eyes, respiratory system and skin . R41:Risk of serious damage to eyes. R37/38:Irritating to respiratory system and skin . R20/21/22:Harmful by inhalation, in contact with skin and if swallowed .
• 安全声明 (欧洲): S26-S36/37/39-S45-S37/39
• 危险品运输编码: UN 2735 8/PG 3
• WGK德国: 3
• RTECS号: FF2200000
• 海关编码: 29252000

合成路线

39512-49-7 37743-18-3 ~77% 53179-11-6

文献：Chen, Zhengming; Davies, Ellen; Miller, Wendy S.; Shan, Shen; Valenzano, Kenneth J.; Kyle, Donald J. Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 21 p. 5275 - 5279

37742-98-6 ~% 53179-11-6

文献：Bioorganic and Medicinal Chemistry Letters, , vol. 14, # 21 p. 5275 - 5279

50650-44-7 ~% 53179-11-6

文献：Bioorganic and Medicinal Chemistry Letters, , vol. 14, # 21 p. 5275 - 5279

956-89-8 ~% 53179-11-6

文献：Bioorganic and Medicinal Chemistry Letters, , vol. 23, # 19 p. 5259 - 5263

上下游产品

上游产品  4
39512-49-7 37743-18-3 37742-98-6 956-89-8
下游产品  0

制备

二苯乙腈和氨基钠作用后，再通入环氧乙烷反应。在反应得到产物中，加入36%溴化氢的冰乙酸溶液，得4-溴-2,2-二苯基丁酸。接着用氧化亚砜氯化酰氯，再在甲苯和水中，通入二甲胺进行酰化，最后和4-羟基-4-对氯苯基哌啶反应，即得洛哌丁胺。

海关

海关编码	29252000