79455-30-4

• 常用中文名：烟拉文
• 常用英文名：Nicaraven
• CAS号：79455-30-4
• 分子式：C₁₅H₁₆N₄O₂
• 分子量：284.313
• 相关类别： 研究领域 癌症
• 发布时间：2018-06-16 21:23:35
• 更新时间：2024-01-03 14:57:28
• Nicaraven是一种新颖的化学合成的羟基自由基清除剂。

名称

• 中文名: 烟拉文
• 英文名: N-[2-(pyridine-3-carbonylamino)propyl]pyridine-3-carboxamide
• 中文别名: N,N'-亚丙基双烟酰胺
• 英文别名: (+-)-N,N'-Propylenebis(nicotinamide); 1,2-Bis(nicotinamido)propane; N,N'-propane-1,2-diyldipyridine-3-carboxamide; Nicaraven; N,N'-1,2-Propanediyldinicotinamide; N,N'-Propylenenicotinamide; N,N'-(Propane-1,2-diyl)dinicotinamide; 3-Pyridinecarboxamide, N,N'-(1-methyl-1,2-ethanediyl)bis-; N,N'-Propane-1,2-diyldinicotinamide; (±)-N,N'-Propylenedinicotinamide; N,N'-propylenedinicotinamide; (±)-1,2-Bis(nicotinamido)propane; Nicaravenum [INN-Latin]

物化性质

• 密度: 1.2±0.1 g/cm3
• 沸点: 635.9±40.0 °C at 760 mmHg
• 分子式: C₁₅H₁₆N₄O₂
• 分子量: 284.313
• 闪点: 338.4±27.3 °C
• 精确质量: 284.127319
• PSA: 83.98000
• LogP: 0.44
• 外观性状: white solid
• 蒸汽压: 0.0±1.9 mmHg at 25°C
• 折射率: 1.584
• 储存条件: -20℃

生物活性

• 描述: Nicaraven是一种新颖的化学合成的羟基自由基清除剂。
• 相关类别:
  信号通路 >> 其他 >> 其他
  研究领域 >> 癌症
• 体外研究: 在健康志愿者血小板中,在浓度范围为350μM或更高的尼加拉文中,二磷酸腺苷(ADP)诱导的最大聚集率被显着抑制。 1.75 mM的nicaraven显着抑制胶原蛋白诱导的最大聚集率[1]。
• 体内研究: Nicaraven抑制肝脏脂质过氧化,改善肝脏和全身血流动力学和能量代谢,抑制肝脏酶释放,肝静脉血内皮素-1升高,组织学损伤和中性粒细胞浸润肝脏[1]。 Nicaraven增加骨髓和外周血中c-kit(+)干/祖细胞的数量,年龄匹配的非照射健康小鼠的恢复率约为60-90％。来自造血干/祖细胞的集落形成作为功能指标的效力完全受到nicaraven治疗的保护[2]。尼卡拉文的给药显着增加了数量,改善了集落形成能力,并减少了造血干/祖细胞的DNA损伤。与接受安慰剂的小鼠相比,给予尼卡拉的小鼠的尿氧水平8-氧代-2'-脱氧鸟苷(DNA氧化的标志物)显着降低。尼卡拉文的给药显着降低了小鼠血浆中炎性细胞因子IL-6和TNF-α的水平[3]。
• 动物实验: 小鼠：为了研究尼卡拉文对造血干/祖细胞辐射损伤的保护作用及相关机制，12只小鼠每天接受1Gyγ射线连续5天（总共5Gy），然后每次暴露后不久，分别给予尼卡拉通（100mg / kg /天，Nicaraven组; n = 6）或仅盐水（安慰剂组; n = 6）腹膜内注射。在最后一次暴露后2天处死小鼠，收集尿液，血液和骨髓细胞样品并用于以下实验[3]。
• 参考文献:

  [1]. Komiya T, et al. A novel free radical scavenger, nicaraven, inhibits human platelet aggregation in vitro. Clin Neuropharmacol. 1999 Jan-Feb;22(1):11-4.

  [2]. Yokota R, et al. A novel hydroxyl radical scavenger, nicaraven, protects the liver from warm ischemia and reperfusion injury. Surgery. 2000 Jun;127(6):661-9.

  [3]. Ali H, et al. The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures.

  [4]. Nicaraven attenuates radiation-induced injury in hematopoietic stem/progenitor cells in mice. PLoS One. 2013;8(3):e60023.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : US4667270 CHEMICAL NAME : 3-Pyridinecarboxamide, N,N'-(1-methyl-1,2-ethanediyl)bis- CAS REGISTRY NUMBER : 79455-30-4 LAST UPDATED : 199612 DATA ITEMS CITED : 9 MOLECULAR FORMULA : C15-H16-N4-O2 MOLECULAR WEIGHT : 284.35 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 840 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory stimulation 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: 23(Suppl 1),S9,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 590 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea Skin and Appendages - hair 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: 23(Suppl 1),S5,1995 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >1 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #0029602 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 1500 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold 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: 23(Suppl 1),S13,1995 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 22680 mg/kg/4W-I TOXIC EFFECTS : Endocrine - changes in adrenal weight Blood - normocytic anemia Nutritional and Gross Metabolic - weight loss or decreased weight gain 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: 23(Suppl 1),S21,1995 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 49140 mg/kg/26W-I TOXIC EFFECTS : Endocrine - changes in spleen weight Blood - normocytic anemia Blood - 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: 23(Suppl 1),S69,1995 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 9450 mg/kg/5W-I TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation Sense Organs and Special Senses (Eye) - effect, not otherwise specified 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: 23(Suppl 1),S41,1995 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 26400 mg/kg/26W-I TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Sense Organs and Special Senses (Eye) - effect, not otherwise specified 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: 23(Suppl 1),S103,1995 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous DOSE : 12 gm/kg SEX/DURATION : male 60 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands 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: 23(Suppl 1),S155,1995

合成路线

6959-48-4 78-90-0 ~% 79455-30-4

文献：US4366161 A1, ;