488-41-5

• 常用中文名：二溴甘露醇
• 常用英文名：1,6-DIBROMO-1,6-DIDEOXY-D-MANNITOL
• CAS号：488-41-5
• 分子式：C₆H₁₂Br₂O₄
• 分子量：307.96500
• 相关类别： 原料药 抗肿瘤药 烷化剂类抗肿瘤药
• 发布时间：2018-09-02 16:59:25
• 更新时间：2024-01-03 01:46:09
• 米托溴醇(Myelobromol；DBM)是甘露醇的溴化类似物,也被称为一种被归类为烷基化剂的抗癌剂。丝裂霉素具有骨髓抑制的潜力,与加速慢性粒细胞白血病中异基因骨髓移植的几种并发症风险显著降低相关[1][2]。

名称

• 中文名: 二溴甘露醇
• 英文名: 1,6-dibromo-1,6-dideoxy-d-mannitol
• 中文别名: 1,6-二溴-1,6-二脱氧-D-甘露糖醇
• 英文别名: r54; 1.6-dibromo-1.6-dideoxy-D-mannitol; 1,6-dibromo-D-1,6-dideoxy-mannitol; 1.6-Dibrom-1.6-didesoxy-D-mannit; dibromannit; dibromomannitol; EINECS 207-676-8; Mielobromol; mieobromol; myelobromol; mitobronitol; myebrol

物化性质

• 密度: 2.117g/cm3
• 沸点: 511.2ºC at 760mmHg
• 熔点: 176-178°
• 分子式: C₆H₁₂Br₂O₄
• 分子量: 307.96500
• 闪点: 263ºC
• 精确质量: 305.91000
• PSA: 80.92000
• 蒸汽压: 1.37E-12mmHg at 25°C
• 折射率: 1.622
• 储存条件: −20°C
• 稳定性:

  遇碱易分解,其水溶液能分解逸出氢溴酸。在干燥空气中稳定,无臭,味微苦。

• 分子结构:

  1、 摩尔折射率：57.47

  2、 摩尔体积（cm³/mol）：183.4

  3、 等张比容（90.2K）：477.7

  4、 表面张力（dyne/cm）：45.9

  5、 极化率（10-24cm3）：22.78

• 更多:

  1. 性状：白色结晶或结晶性粉末。

  2. 熔点（ºC）：187。

  3. 溶解性：易溶于浓氢溴酸及DMF。略溶于乙醇,微溶于水和丙酮。

生物活性

• 描述: 米托溴醇(Myelobromol；DBM)是甘露醇的溴化类似物,也被称为一种被归类为烷基化剂的抗癌剂。丝裂霉素具有骨髓抑制的潜力,与加速慢性粒细胞白血病中异基因骨髓移植的几种并发症风险显著降低相关[1][2]。
• 相关类别:
  研究领域 >> 癌症
  信号通路 >> 细胞周期/DNA损伤 >> DNA烷基化剂/交联剂
• 体内研究: 在小鼠模型中,丝裂霉素(850 mg/kg；i.p.；单剂量)提高脾细胞对有丝分裂原的敏感性,并促进胸腺再生[2]。动物模型：雌性BALB/c小鼠(8-10周龄)[2]剂量：850 mg/kg；1500 mg/kg(悬浮于5%吐温80盐水中,0.5 mL)给药：腹膜内注射；单剂量结果：850mg/kg剂量对脾细胞对有丝分裂原的体外增殖反应有影响。在1500 mg/kg剂量下,胸腺再生增强,比对照早,开始恢复时间为2周,次全恢复时间为3周。

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : OP2800000 CHEMICAL NAME : Mannitol, 1,6-dibromo-1,6-dideoxy-, D- CAS REGISTRY NUMBER : 488-41-5 BEILSTEIN REFERENCE NO. : 1721919 LAST UPDATED : 199707 DATA ITEMS CITED : 36 MOLECULAR FORMULA : C6-H12-Br2-O4 MOLECULAR WEIGHT : 308.00 WISWESSER LINE NOTATION : E1YQYQYQYQ1E 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 : 1500 mg/kg TOXIC EFFECTS : Gastrointestinal - hypermotility, diarrhea Gastrointestinal - other changes Blood - normocytic anemia TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 900 mg/kg TOXIC EFFECTS : Blood - normocytic anemia Blood - thrombocytopenia TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1240 mg/kg TOXIC EFFECTS : Gastrointestinal - hypermotility, diarrhea Gastrointestinal - other changes Blood - normocytic anemia TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1370 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1380 mg/kg TOXIC EFFECTS : Behavioral - tremor Behavioral - ataxia Skin and Appendages - hair TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 900 mg/kg TOXIC EFFECTS : Behavioral - tremor Behavioral - ataxia Skin and Appendages - hair TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 2200 mg/kg TOXIC EFFECTS : Behavioral - tremor Behavioral - ataxia Skin and Appendages - hair TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 2200 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 1080 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 : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 4950 mg/kg/33D-I TOXIC EFFECTS : Behavioral - ataxia Liver - other changes Blood - changes in leukocyte (WBC) count TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 5460 mg/kg/26W-I TOXIC EFFECTS : Endocrine - changes in thymus weight Blood - normocytic anemia Related to Chronic Data - death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 10920 mg/kg/26W-C TOXIC EFFECTS : Related to Chronic Data - changes in testicular weight TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 9750 mg/kg/26W-I TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Skin and Appendages - tumors Tumorigenic - tumors at site of application TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 7000 mg/kg/26W-I TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors Blood - lymphoma, including Hodgkin's disease TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 300 mg/kg SEX/DURATION : female 9-14 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 : Oral DOSE : 3900 mg/kg SEX/DURATION : female 26 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Maternal Effects - uterus, cervix, vagina TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 500 mg/kg SEX/DURATION : female 13 day(s) after conception TOXIC EFFECTS : 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 : 500 mg/kg SEX/DURATION : female 10 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - urogenital system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 300 mg/kg SEX/DURATION : female 9 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 - fetal death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 3900 mg/kg SEX/DURATION : male 26 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 150 mg/kg SEX/DURATION : female 11 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 - Effects on Embryo or Fetus - fetal death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 150 mg/kg SEX/DURATION : female 11 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 300 mg/kg SEX/DURATION : female 12 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear TYPE OF TEST : Sex chromosome loss and nondisjunction TYPE OF TEST : Heritable translocation test TYPE OF TEST : Cytogenetic analysis TYPE OF TEST : Sister chromatid exchange MUTATION DATA TYPE OF TEST : DNA inhibition TEST SYSTEM : Rodent - rabbit Bone marrow DOSE/DURATION : 730 umol/L REFERENCE : BCPCA6 Biochemical Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1958- Volume(issue)/page/year: 25,1705,1976 *** REVIEWS *** TOXICOLOGY REVIEW CRTXB2 CRC Critical Reviews in Toxicology. (CRC Press, Inc., 2000 Corporate Blvd., NW, Boca Raton, FL 33431) V.1- 1971- Volume(issue)/page/year: 1(1),93,1971 TOXICOLOGY REVIEW CRTXB2 CRC Critical Reviews in Toxicology. (CRC Press, Inc., 2000 Corporate Blvd., NW, Boca Raton, FL 33431) V.1- 1971- Volume(issue)/page/year: 2,159,1973

安全

• 危害码 (欧洲): T: Toxic;
• 风险声明 (欧洲): 45-22
• 安全声明 (欧洲): S22;S45;S53;S36/S37/S39
• WGK德国: 3
• RTECS号: OP2800000
• 海关编码: 2905590090

合成路线

69-65-8 ~% 488-41-5

文献：Institoris; Horvath; Csanyi Arzneimittel-Forschung, 1967 , vol. 17, # 2 p. 145 - 149 Title/Abstract Full Text View citing articles Show Details Samoilova,O.I. et al. J. Gen. Chem. USSR (Engl. Transl.), 1973 , vol. 43, p. 365 - 369,363 - 366

641-74-7 ~% 488-41-5

文献：Overend et al. Journal of the Chemical Society, 1948 , p. 2201

506-96-7 69-65-8 ~% 488-41-5

文献：Fidalgo, Daniela M.; Kolender, Adriana A.; Varela, Oscar Journal of Polymer Science, Part A: Polymer Chemistry, 2013 , vol. 51, # 2 p. 463 - 470

19895-66-0 ~% 488-41-5

文献：Jarman,M.; Ross,W.C.J. Carbohydrate Research, 1969 , vol. 9, p. 139 - 147

17107-32-3 ~% 488-41-5 100778-28-7 32739-56-3 详细

文献：Kuszmann, Janos Carbohydrate Research, 1985 , vol. 142, p. 71 - 84

56-23-5 7789-60-8 641-74-7 ~% 488-41-5

文献：Overend et al. Journal of the Chemical Society, 1948 , p. 2201

制备

由D-甘露醇与氢溴酸反应得到二溴甘露醇:
将甘露醇溶解于氢溴酸,加热回流3h。加水稀释并降温至52℃,加入活性炭脱色。过滤,将滤液降温至20℃,搅拌下用碳酸氢钠调节pH1~2,冷冻后甩滤、水洗、氯仿洗涤,真空干燥后用甲醇重结晶、活性炭脱色精制而得成品。收率约36%。

海关

海关编码	2905590090
中文概述	2905590090 其他无环醇的卤化、磺化等衍生物。监管条件:无。增值税率:17.0%。退税率:9.0%。最惠国关税:5.5%。普通关税:30.0%
申报要素	品名, 成分含量, 用途, 包装
Summary	2905590090 other halogenated, sulphonated, nitrated or nitrosated derivatives of acyclic alcohols。Supervision conditions:None。VAT:17.0%。Tax rebate rate:9.0%。MFN tariff:5.5%。General tariff:30.0%