81840-15-5

• 常用中文名：维司力农
• 常用英文名：Vesnarinone
• CAS号：81840-15-5
• 分子式：C₂₂H₂₅N₃O₄
• 分子量：395.45200
• 相关类别： 原料药 循环系统用药 治疗慢性心功能不全药
• 发布时间：2018-09-11 17:36:24
• 更新时间：2024-01-04 23:02:40
• Vesnarinone是一种喹啉酮衍生物, 药效学效应包括抑制磷酸二酯酶III (PDE3) 活性,增加钙通量, 及减小钾通量。

名称

• 中文名: 维司力农
• 英文名: 6-[4-(3,4-dimethoxybenzoyl)piperazin-1-yl]-3,4-dihydro-1H-quinolin-2-one
• 中文别名: 3,4-二氢-6-[4-(3,4-二甲氧苯甲酰)-1-哌嗪基]-2(1H)-喹啉酮; 威那利酮
• 英文别名: vesnarinone; Piteranometozine; 6-[4-(3,4-dimethoxy-benzoyl)-1-piperazinyl]-3,4-dihydrocarbostyril; Arkin-Z; 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinoline; DRG-0210; OPC8212

物化性质

• 密度: 1.246g/cm3
• 沸点: 678.3ºC at 760 mmHg
• 熔点: 238.1-239.5° (Tominaga); mp 238.1-239.8° (Shimizu)
• 分子式: C₂₂H₂₅N₃O₄
• 分子量: 395.45200
• 闪点: 364ºC
• 精确质量: 395.18500
• PSA: 71.11000
• LogP: 2.69180
• 折射率: 1.601
• 储存条件: 2-8℃
• 分子结构:

  1、 摩尔折射率：108.67

  2、 摩尔体积（cm³/mol）：317.1

  3、 等张比容（90.2K）：843.9

  4、 表面张力（dyne/cm）：50.1

  5、 极化率（10-24cm3）：43.08

• 计算化学:

  1.疏水参数计算参考值（XlogP）:2.1

  2.氢键供体数量:1

  3.氢键受体数量:5

  4.可旋转化学键数量:4

  5.互变异构体数量:3

  6.拓扑分子极性表面积71.1

  7.重原子数量:29

  8.表面电荷:0

  9.复杂度:593

  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：从乙醇-氯仿得无色颗粒状结晶。

  2.熔点238.1-239.5℃.也有无臭无味的淡黄色结晶性粉末,熔点238.1-239.8℃.

  3.UV最大吸收(甲醇，乙醇，氯仿)：271nm(ε25100，25200，23000，C=10μg/m1)。

  4.溶解度%(25℃)：冰醋酸18.68,氯仿14.19,苄醇5.913,N-甲基-2-吡咯啉酮3.407,二甲亚砜2.509,环丁砜1.229,二甲基甲酰胺1.179,二氧六环0.1653,甲醇0.1151,丙酮0.06389,乙醇0.04005,水0.002086。

  5.pKa 2.86。

生物活性

• 描述: Vesnarinone是一种喹啉酮衍生物, 药效学效应包括抑制磷酸二酯酶III (PDE3) 活性,增加钙通量, 及减小钾通量。
• 相关类别:
  信号通路 >> 代谢酶/蛋白酶 >> 磷酸二酯酶(PDE)
  研究领域 >> 感染
• 参考文献:

  [1]. Katayama Y, et al. Inhibitory effects of Vesnarinone on cloned cardiac delayed rectifier K(+) channels expressed in a mammalian cell line. J Pharmacol Exp Ther. 2000 Jul;294(1):339-46.

  [2]. Inage M, et al. Vesnarinone represses the fibrotic changes in murine lung injury induced by bleomycin. Int J Biol Sci. 2009;5(4):304-10.

  [3]. Cavusoglu E, et al. Vesnarinone: a new inotropic agent for treating congestive heart failure. J Card Fail. 1995 Jun;1(3):249-57.

  [4]. Matsumori A, et al. Vesnarinone, a new inotropic agent, inhibits cytokine production by stimulated human blood from patients with heart failure. Circulation. 1994 Mar;89(3):955-8.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : TL4490000 CHEMICAL NAME : Piperazine, 1-(3,4-dimethoxybenzoyl)-4-(1,2,3,4-tetrahydro-2-oxo- 6-quinolinyl)- CAS REGISTRY NUMBER : 81840-15-5 LAST UPDATED : 199612 DATA ITEMS CITED : 16 MOLECULAR FORMULA : C22-H25-N3-O4 MOLECULAR WEIGHT : 395.50 WISWESSER LINE NOTATION : T66 BNVT&J H- AT6N DNTJ DVR CO1 DO1 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 : >7594 mg/kg TOXIC EFFECTS : Liver - other changes Kidney, Ureter, Bladder - other changes 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: 18,922,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >1200 mg/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - other changes Liver - other changes Kidney, Ureter, Bladder - other changes 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: 18,922,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >3 gm/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - other changes Liver - other changes Kidney, Ureter, Bladder - other changes 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: 18,922,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 79300 ug/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - changes in structure or function of salivary glands 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: 18,922,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >7594 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Skin and Appendages - hair Nutritional and Gross Metabolic - body temperature decrease 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: 18,922,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >1200 mg/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - other changes Liver - other changes Kidney, Ureter, Bladder - other changes 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: 18,922,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >1200 mg/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - other changes Liver - other changes Kidney, Ureter, Bladder - other changes 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: 18,922,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 56300 ug/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - changes in structure or function of salivary glands 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: 18,922,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >3 gm/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - other changes Liver - other changes Kidney, Ureter, Bladder - other changes 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: 18,922,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 63300 ug/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - changes in structure or function of salivary glands 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: 18,922,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : >3 gm/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: 18,922,1987 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 1100 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) Reproductive - Effects on Newborn - behavioral 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: 18,875,1987 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 330 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system 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: 18,875,1987 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 11 gm/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Specific Developmental Abnormalities - eye/ear 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: 18,875,1987 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 3900 mg/kg SEX/DURATION : female 6-18 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death 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: 18,898,1987 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 13 gm/kg SEX/DURATION : female 6-18 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - musculoskeletal system 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: 18,898,1987

合成路线

22246-13-5 81840-14-4 ~% 81840-15-5

文献：Otsuka Pharmaceutical Co., Ltd. Patent: US4415572 A1, 1983 ;

87154-95-8 86813-31-2 3535-37-3 ~% 81840-15-5

文献：Otsuka Pharmaceutical Co., Ltd. Patent: US4415572 A1, 1983 ;

86813-31-2 3535-37-3 ~68% 81840-15-5

文献：Tominaga; Yo; Ogawa; Yamashita; Yabuuchi; Nakagawa Chemical and Pharmaceutical Bulletin, 1984 , vol. 32, # 6 p. 2100 - 2110

22246-13-5 ~% 81840-15-5

文献：Tominaga; Yo; Ogawa; Yamashita; Yabuuchi; Nakagawa Chemical and Pharmaceutical Bulletin, 1984 , vol. 32, # 6 p. 2100 - 2110

43204-63-3 ~% 81840-15-5

文献：Tominaga; Yo; Ogawa; Yamashita; Yabuuchi; Nakagawa Chemical and Pharmaceutical Bulletin, 1984 , vol. 32, # 6 p. 2100 - 2110

上下游产品

上游产品  6
22246-13-5 81840-14-4 87154-95-8 86813-31-2
3535-37-3 43204-63-3
下游产品  3
3943-77-9 93-07-2 87154-95-8

制备

以6-氨基-3，4-二氢-2(1H)-喹啉酮为原料。将6-氨基-3，4-二氢-2(1H)-喹啉酮(21.1g，0.13mo1)和双(伊溴乙基)胺氢溴酸盐(40.5g，0.13mo1)溶于150ml乙醇，回流搅拌8h。冷却，加入碳酸钠(13.8g，0.13mo1)，再回流搅拌8h。冷至室温，过滤收集析出的沉淀，用乙醇洗，乙醇-水重结晶，得26.4g无色针状结晶的3，4-二氢-6-(1-哌嗪基)-2(1H)-喹啉酮氢溴酸盐，收率64%，熔点289--293℃(分解)。
将上述得到的喹啉酮衍生物(3.1g，0.010mo1)和三乙胺(2.2g，0.022mo1)溶于40ml无水二甲基甲酰胺，在冰浴冷却和搅拌下，滴加3，4-二甲氧苯甲酰氯(2.2g，0.0l 1mo1)在10ml无水二甲基甲酰胺中的溶液。加毕，在室温下搅拌1h。将反应液倾入冰水，用氯仿提取。提取液水洗，无水硫酸钠干燥，减压浓缩。剩余物用硅胶层析，氯仿-甲醇(100：1)洗脱。然后再用乙醇-氯仿重结晶，得2.7g无色颗粒状结晶的维司力农，收率70%，熔点238～239.5℃。