52-53-9

• 常用中文名：维拉帕米
• 常用英文名：Verapamil
• CAS号：52-53-9
• 分子式：C₂₇H₃₈N₂O₄
• 分子量：454.602
• 相关类别： 原料药 循环系统用药 抗心律失常药
• 发布时间：2018-09-06 20:52:31
• 更新时间：2026-07-01 10:48:03
• Verapamil ((±)-Verapamil) 是一种钙通道 (calcium channel) 阻滞剂,是一种有效的口服活性的第一代 P 糖蛋白 (P-gp) 抑制剂。Verapamil 能也抑制 CYP3A4,并可用于高血压,心律不齐和心绞痛的研究。

名称

• 中文名: 维拉帕米
• 英文名: 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile
• 中文别名: 维拉帕米(异博定); 维拉帕米杂质N; 维拉帕米杂质P; 维拉帕米 Verapamil; 维拉帕米相关杂质; 维拉帕米检测标准品; Verapamil 活性化合物; 维拉帕米,10 MM DMSO 溶液; 戊脉胺; 5-((3,4-二甲氧基苯乙基)甲基氨基)-2-(3,4-二甲氧基苯基)-2-异丙基戊腈; 异博定
• 英文别名: Valeronitrile, 5-[(3,4-dimethoxyphenethyl)methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropyl- (7CI, 8CI); EINECS 200-145-1; 5-[(3,4-Dimethoxyphenethyl)methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile; a-((N-Methyl-N-homoveratryl)-g-aminopropyl)-3,4-dimethoxyphenylacetonitrile; benzeneacetonitrile,alpha-(3-((2-(3,4-dimethoxyphenyl)ethyl)methylamino)propy; 16533-1; Benzeneacetonitrile, alpha-[3-[[2-(3,4-dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy-alpha-(1-methylethyl); 2-isopropyl; 2-(3,4-Dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-isopropylpentanenitrile; a-[3-[[2-(3,4-Dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy-a-(1-methylethyl)benzeneacetonitrile; VERAPAMIL; eronitrile; verapamile; 5-((3,4-dimethoxyphenethyl)methylamino)-2-(3,4-dimethoxyphenyl)-2-isopropylval; oxyphenylacetonitrile; Valeronitrile, 5-((3,4-dimethoxyphenethyl)methylamino)-2-(3,4-dimethoxyphenyl)-2-isopropyl; Verapamil (base and/or unspecified salts); 2-(3,4-Dimethoxyphenyl)-5-[[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino]-2-isopropylpentanenitrile; R,S-Verapamil; (2R)-2-(3,4-diMethoxyphenyl)-5-{[2-(3,4-diMethoxyphenyl)ethyl](Methyl)amino}-2-(propan-2-yl)pentanenitrile; 2-(3,4-Dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]-2-propan-2-ylpentanenitrile; alpha-[3-[[2-(3,4-Dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy-alpha-(1-methylethyl)benzeneacetonitrile; alpha-[3-[[2-(3,4-dimethoxyphenyl)ethyl]-methylamino]propyl]-3,4-dimethoxy-alp; (2S)-2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]-2-propan-2-ylpentanenitrile; Vasolan; (+/-) VERAPAMIL; a-Isopropyl-a-[(N-methyl-N-homoveratryl)-g-aminopropyl]-3,4-dimethoxyphenylacetonitrile; 5-((3,4-Dimethoxyphenethyl)(methyl)amino)-2-(3,4-dimethoxyphenyl)-2-isopropylpentanenitrile; 5-((3,4-Dimethoxyphenethyl)methylamino)-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile; VerapamilQ: What is Verapamil Q: What is the CAS Number of Verapamil Q: What is the storage condition of Verapamil Q: What e the applications of Verapamil; dl-Verapamil; aleronitrile; Verapamil in methanol; Benzeneacetonitrile, α-[3-[[2-(3,4-dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy-α-(1-methylethyl); (2R)-2-(3,4-Dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-isopropylpentanenitrile; alpha-((N-Methyl-N-homoveratryl)-gamma-aminopropyl)-3,4-dimethoxyphenylacetonitrile; 16(Verapamil); alpha-((n-methyl-n-homoveratryl)-gamma-aminopropyl)-3,4-dimethoxyphenylaceto; Dilacoran; VPL; valeronitrile,5-((3,4-dimethoxyphenethyl)methylamino)-2-(3,4-dimethoxyphenyl); Verapamil, 10 mM in DMSO; Verapamil //BP; 5-((3,4-dimethoxyphenethyl)methylamino)-2-(3,4-dimethoxyphenyl)-2-isopropylv; VerapamilC27H38N204; Benzeneacetonitrile, .alpha.-(3,4-dimethoxyphenyl)ethylmethylaminopropyl-3,4-dimethoxy-.alpha.-(1-methylethyl); MFCD00056240; alpha-isopropyl-alpha-[(n-methyl-n-homoveratryl)-gamma-aminopropyl]-3,4-dimeth; 4-dimethoxy-alpha-(1-methylethyl)-l); ha-(1-methylethyl)benzeneacetonitrile; verapaiTiil; Lekoptin; NSC 272306NA; Benzeneacetonitrile, a-[3-[[2-(3,4-dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy-a-(1-methylethyl)- (9CI); (±)-Verapamil; D-365; CP 16533-1

物化性质

• 密度: 1.1±0.1 g/cm3
• 沸点: 586.2±50.0 °C at 760 mmHg
• 熔点: 25°C
• 分子式: C₂₇H₃₈N₂O₄
• 分子量: 454.602
• 闪点: 308.3±30.1 °C
• 精确质量: 454.283173
• PSA: 63.95000
• LogP: 3.90
• 外观性状: 黏的,淡黄色油状
• 蒸汽压: 0.0±1.6 mmHg at 25°C
• 折射率: 1.526
• 储存条件: 室温
• 分子结构:

  1、 摩尔折射率：131.86

  2、 摩尔体积（cm³/mol）：429.3

  3、 等张比容（90.2K）：1063.9

  4、 表面张力（dyne/cm）：37.6

  5、 极化率（10-24cm3）：52.27

• 计算化学:

  1.疏水参数计算参考值（XlogP）:无

  2.氢键供体数量:0

  3.氢键受体数量:6

  4.可旋转化学键数量:13

  5.互变异构体数量:无

  6.拓扑分子极性表面积64

  7.重原子数量:33

  8.表面电荷:0

  9.复杂度:606

  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：粘稠的淡黄色油状液体。

  2.沸点（℃）：243-246（1.3Pa）。

  3.折光率（nD25）：1.5448。

  4.溶解性：溶于苯、醚，易溶于低级醇、丙酮、乙酸乙酯、氯仿，难溶于已烷，不溶于水。

生物活性

• 描述: Verapamil ((±)-Verapamil) 是一种钙通道 (calcium channel) 阻滞剂,是一种有效的口服活性的第一代 P 糖蛋白 (P-gp) 抑制剂。Verapamil 能也抑制 CYP3A4,并可用于高血压,心律不齐和心绞痛的研究。
• 相关类别:
  信号通路 >> 跨膜转运 >> 钙通道
  信号通路 >> 代谢酶/蛋白酶 >> 细胞色素P450
  信号通路 >> 跨膜转运 >> P-糖蛋白
  研究领域 >> 代谢疾病
• 靶点:

  Calcium channel[1] Permeability-glycoprotein (P-gp)[1] CYP3A4[1]

• 体外研究: 阳离子药物抑制TR-iBRB2细胞对everfulu-FL-Verapamil(EFV)的摄取,并以浓度依赖性方式抑制Verapamil,IC50为98.0μM[4]。
• 体内研究: 静脉注射维拉帕米对终止阵发性往复式房室性心动过速非常有效,无论是与预激相关还是仅累及房室结[2]。口服对预防房室折返性心动过速和调节房颤时的房室结反应是有用的[2]。
• 参考文献:

  [1]. Gowarty JL, et al. Verapamil as a culprit of palbociclib toxicity. J Oncol Pharm Pract. 2019 Apr;25(3):743-746.

  [2]. Krikler DM. Verapamil in arrhythmia. Br J Clin Pharmacol. 1986;21 Suppl 2:183S-189S.

  [3]. Rehnqvist N,et al. Effects of metoprolol vs verapamil in patients with stable angina pectoris. The Angina Prognosis Study in Stockholm (APSIS). Eur Heart J. 1996 Jan;17(1):76-81.

  [4]. Kubo Y, et al. Blood-to-Retina Transport of Fluorescence-Labeled Verapamil at the Blood-Retinal Barrier. Pharm Res. 2018 Mar 12;35(5):93.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : YV8300000 CHEMICAL NAME : Valeronitrile, 5-((3,4-dimethoxyphenethyl)methylamino)-2-(3,4-dimeth oxyphenyl)-2-isopropy l- CAS REGISTRY NUMBER : 52-53-9 LAST UPDATED : 199801 DATA ITEMS CITED : 19 MOLECULAR FORMULA : C27-H38-N2-O4 MOLECULAR WEIGHT : 454.67 WISWESSER LINE NOTATION : 1OR BO1 DXCN&Y1&1&3N1&2R CO1 DO1 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 80 mg/kg TOXIC EFFECTS : Behavioral - coma Cardiac - pulse rate increase, without fall in BP Vascular - BP lowering not characterized in autonomic section REFERENCE : HETOEA Human & Experimental Toxicology. (Macmillan Press Ltd., Brunel Road, Houndmills, Basingstoke, Hampshire, RG21 2XS, UK) V.9- 1990- Volume(issue)/page/year: 16,35,1997 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 46 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Cardiac - EKG changes not diagnostic of specified effects Vascular - BP lowering not characterized in autonomic section REFERENCE : CTOXAO Clinical Toxicology. (New York, NY) V.1-18, 1968-81. For publisher information, see JTCTDW. Volume(issue)/page/year: 17,395,1980 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 2 gm/kg TOXIC EFFECTS : Sense Organs and Special Senses (Olfaction) - effect, not otherwise specified Cardiac - other changes Vascular - BP lowering not characterized in autonomic section REFERENCE : CHETBF Chest. (American College of Chest Physicians, 911 Busse Hwy, Park Ridge, IL 60068) V.57- 1970- Volume(issue)/page/year: 75,200,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 64 mg/kg TOXIC EFFECTS : Cardiac - pulse rate Cardiac - change in rate Vascular - BP lowering not characterized in autonomic section REFERENCE : BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 2,1127,1978 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 48 mg/kg/2W-I TOXIC EFFECTS : Liver - hepatitis (hepatocellular necrosis), diffuse REFERENCE : NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year: 306,612,1982 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 83 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Cardiac - cardiomyopathy including infarction Vascular - BP lowering not characterized in autonomic section REFERENCE : AJEMEN American Journal of Emergency Medicine. (WB Saunders, Philadelphia, PA) V.1- 1983- Volume(issue)/page/year: 7,624,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 3429 ug/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Cardiac - pulse rate Lungs, Thorax, or Respiration - acute pulmonary edema REFERENCE : CCMDC7 Critical Care Medicine. (Williams & Wilkins, 428 E. Preston Street, Baltimore, MD 21202) V.1- 1973- Volume(issue)/page/year: 19,436,1991 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Human - man DOSE/DURATION : 1429 ug/kg/5M-C TOXIC EFFECTS : Cardiac - pulse rate Lungs, Thorax, or Respiration - cyanosis Skin and Appendages - sweating REFERENCE : NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year: 306,238,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Human - man DOSE/DURATION : 71 ug/kg TOXIC EFFECTS : Cardiac - pulse rate increase, without fall in BP Lungs, Thorax, or Respiration - dyspnea REFERENCE : AHJOA2 American Heart Journal. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1925- Volume(issue)/page/year: 111,622,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Human - child DOSE/DURATION : 250 ug/kg/5M-C TOXIC EFFECTS : Cardiac - arrhythmias (including changes in conduction) REFERENCE : AHJOA2 American Heart Journal. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1925- Volume(issue)/page/year: 106,145,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 163 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : EJMCA5 European Journal of Medicinal Chemistry--Chimie Therapeutique. (Editions Scientifiques Elsevier, 29 rue Buffon, F-75005, Paris, France) V.9- 1974- Volume(issue)/page/year: 25,351,1990 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 7250 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : PCJOAU Pharmaceutical Chemistry Journal (English Translation). Translation of KHFZAN. (Plenum Pub. Corp., 233 Spring St., New York, NY 10013) No.1- 1967- Volume(issue)/page/year: 22,123,1988 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 130 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : FATOAO Farmakologiya i Toksikologiya (Moscow). For English translation, see PHTXA6 and RPTOAN. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.2- 1939- Volume(issue)/page/year: 54(2),40,1991 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 43 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JDGRAX Journal of Drug Research. (National Organization for Drug Research and Control, POB 29, Cairo, Egypt) V.2- 1969- Volume(issue)/page/year: 15(1-2),121,1984 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 30770 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JPPMAB Journal of Pharmacy and Pharmacology. (Pharmaceutical Soc. of Great Britain, 1 Lambeth High St., London SEI 7JN, UK) V.1- 1949- Volume(issue)/page/year: 34,329,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1520 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : EJTXAZ European Journal of Toxicology and Environmental Hygiene. (Paris, France) V.7-9, 1974-76. For publisher information, see TOERD9. Volume(issue)/page/year: 8,188,1975 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 51 mg/kg SEX/DURATION : male 30 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - breast development REFERENCE : MJAUAJ Medical Journal of Australia. (Australasian Medical Pub. Co. Ltd., 71-79 Arundel St., Glebe, N.S.W., Australia) V.1- 1914- Volume(issue)/page/year: 161,328,1994 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 60 mg/kg SEX/DURATION : female 10-12 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system REFERENCE : REPTED Reproductive Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1987- Volume(issue)/page/year: 11,207,1997 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4662 No. of Facilities: 65 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 14268 (estimated) No. of Female Employees: 7372 (estimated)

安全

• 危害码 (欧洲): C
• 风险声明 (欧洲): R14:Reacts violently with water. R34:Causes burns. R37:Irritating to the respiratory system.
• 安全声明 (欧洲): S26-S36/37/39-S43-S45
• 危险品运输编码: UN 1939 8/PG 2
• WGK德国: 3
• 包装等级: II
• 危险类别: 8

合成路线

871703-17-2 3490-06-0 ~80% 52-53-9

文献：Wu, Lingyun; Hartwig, John F. Journal of the American Chemical Society, 2005 , vol. 127, # 45 p. 15824 - 15832

625-28-5 ~% 52-53-9

文献：Wu, Lingyun; Hartwig, John F. Journal of the American Chemical Society, 2005 , vol. 127, # 45 p. 15824 - 15832

128776-24-9 ~% 52-53-9

文献：Wu, Lingyun; Hartwig, John F. Journal of the American Chemical Society, 2005 , vol. 127, # 45 p. 15824 - 15832

上下游产品

上游产品  4
871703-17-2 3490-06-0 625-28-5 128776-24-9
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27487-66-7 34245-14-2 67018-85-3 71539-08-7
38321-02-7 36622-29-4

制备

二甲氧基苯乙腈与溴异丙烷进行烃化反应后，与1，3-氯溴丙烷进行氯丙基化反应，然后与3，4-二甲氧基苯乙胺缩合制成维拉帕米。