21416-87-5

• 常用中文名：雷佐生
• 常用英文名：razoxane
• CAS号：21416-87-5
• 分子式：C₁₁H₁₆N₄O₄
• 分子量：268.26900
• 相关类别： 原料药 抗肿瘤药 其它抗肿瘤药
• 发布时间：2018-03-02 08:00:00
• 更新时间：2024-01-05 10:14:57
• 消旋体为抗肿瘤药。用于辅助手术治疗，防止癌肿的转移，急性白血病，急性肉状细胞增多症，也可用于肺癌、胃癌、肝癌、乳腺癌及淋巴肉瘤等。(+)-构型用于cardioprotectant。用于乳腺癌患者的保护，和防止用蒽环类抗生素如阿霉素化疗时对心脏的副作用。
  

名称

• 中文名: 雷佐生
• 英文名: razoxane
• 中文别名: (±)-1,2-双(3,5-二氧哌嗪基)丙烷; 拉唑沙
• 英文别名: Zinecard; ICRF-187; Propane, (.+-.)-1,2-bis(3,5-dioxopiperazin-1-yl)-; ICRF-159; ICRF; Eucardion; Razoxane; Razoxin

物化性质

• 密度: 1.2576 (rough estimate)
• 沸点: 882.3ºC at 760 mmHg
• 熔点: 193ºC
• 分子式: C₁₁H₁₆N₄O₄
• 分子量: 268.26900
• 闪点: 487.4ºC
• 精确质量: 268.11700
• PSA: 98.82000
• 蒸汽压: 1.08E-31mmHg at 25°C
• 折射率: 1.6081 (estimate)
• 稳定性:

  (+)-构(Dexrazoxane)：[24584-09-6]。从含水甲醇-乙醚结晶，熔点193℃。[α]_D+11.35°(C=5，二甲基甲酰胺)。溶解度(mg/ml)：10～12(水)，35～43(0.1mol/L盐酸)，25～34(0.1mol/L氢氧化钠)，6.7～10(10%乙醇)，1(甲醇)，7.1～10[水-二甲基甲酰胺(1：1)]，9.7～14.5[0.1mol/L柠檬酸盐缓冲液(Ph值4)]，8.7～13[0.1mol/L硼酸缓冲液(Ph值9)]。

• 分子结构:

  1、 摩尔折射率：63.12

  2、 摩尔体积（cm³/mol）：201.2

  3、 等张比容（90.2K）：539.3

  4、 表面张力（dyne/cm）：51.6

  5、 极化率（10-24cm3）：25.02

• 计算化学:

  1.疏水参数计算参考值（XlogP）:-1.4

  2.氢键供体数量:2

  3.氢键受体数量:6

  4.可旋转化学键数量:3

  5.互变异构体数量:25

  6.拓扑分子极性表面积98.8

  7.重原子数量:19

  8.表面电荷:0

  9.复杂度:404

  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：白色或近白色或淡米黄色结晶或结晶性粉末，无臭，味微苦。

  2.熔点：233-234℃(分解)，熔点237-239℃。

  3.溶解度：.可溶于热水，难溶于水或乙醇。

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : TL6400000 CHEMICAL NAME : 2,6-Piperazinedione, 4,4'-propylenedi-, (+-)- CAS REGISTRY NUMBER : 21416-87-5 LAST UPDATED : 199612 DATA ITEMS CITED : 19 MOLECULAR FORMULA : C11-H16-N4-O4 MOLECULAR WEIGHT : 268.31 WISWESSER LINE NOTATION : T6VMV ENTJ E3- ET6VMV ENTJ HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 81 mg/kg/3D-I TOXIC EFFECTS : Gastrointestinal - nausea or vomiting Blood - leukopenia Blood - thrombocytopenia TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 500 mg/kg TOXIC EFFECTS : Gastrointestinal - nausea or vomiting Blood - leukopenia Blood - thrombocytopenia TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 861 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 7488 mg/kg/52W-I TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Reproductive - Tumorigenic effects - uterine tumors TYPE OF TEST : TD - Toxic dose (other than lowest) ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 15 gm/kg/Y-I TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Reproductive - Tumorigenic effects - uterine tumors TYPE OF TEST : TD - Toxic dose (other than lowest) ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 12 gm/kg/Y-I TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Blood - lymphoma, including Hodgkin's disease TYPE OF TEST : TD - Toxic dose (other than lowest) ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1 gm/kg/8W-I TOXIC EFFECTS : Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 37500 ug/kg SEX/DURATION : female 6-8 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 37500 ug/kg SEX/DURATION : female 6-8 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - body wall Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 30 mg/kg SEX/DURATION : female 6-8 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 37500 mg/kg SEX/DURATION : female 6-8 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 - other developmental abnormalities TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 10 mg/kg SEX/DURATION : female 8 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 15 mg/kg SEX/DURATION : female 6-8 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported DOSE : 2520 mg/kg SEX/DURATION : male 42 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - testes, epididymis, sperm duct TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 105 mg/kg SEX/DURATION : female 6-8 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) MUTATION DATA TYPE OF TEST : Mutation in mammalian somatic cells TEST SYSTEM : Rodent - mouse Lung DOSE/DURATION : 200 ug/L REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 157,199,1985

制备

1. 100g的1,2-丙二胺四乙酸和400ml甲酰胺，在氮气保护下，于100～110℃共热1h，再于150-155℃共热4h。所成的棕色的溶液在减压下，于80-90℃下蒸去溶剂。剩余物溶入120ml甲醇，在冰箱中放置过夜。过滤，用甲醇洗，在65℃下真空干燥，得到62g淡米黄色的雷佐生细微结晶，收率70%，熔点237～239℃。

2. 在反应瓶中加入1,2-丙二胺四乙酸(1,2-diaminopropane-N,N,N,N-tetraacetic acid) 100g(0.326mol)和甲酰胺NH2COH 400ml(10.01mol),搅拌混合,于N2保护下在100~110ºC搅拌反应1h,再升温至150~155ºC,在该温度下搅拌反应4h.棕色反应液于80~90ºC下减压蒸除溶剂,剩余物加入甲醇120ml,置于冰箱中过夜.析出结晶,过滤,滤饼用甲醇洗,65ºC下真空干燥,得雷佐生淡米黄色结晶62g,收率70%,mp237~239ºC.