制备方法

胸腺嘧啶脱氧核苷和三苯基膦溶于二甲基甲酰胺中,缓慢滴入对甲氧基苯甲酸和偶氮二甲酸二乙酯(DEAD)溶于二甲基甲酰胺所成的溶液,在室温下搅拌后,再补加三苯基膦和DEAD。搅拌反应后,将反应液倒入乙醚,在0℃下放置过夜。过滤出的固体用小量乙醚洗,干燥,得酯化的氧桥物,收率84.1%。该氧桥物和叠氮钠在二甲基甲酰胺中,于125℃搅拌。冷到室温,将其倒入5%盐酸中,用醋酸乙酯提取。提取液用20%氯化钠溶液洗至中性,干燥,浓缩,真空干燥得叠氮衍生物,收率81.8%。叠氮衍生物和甲醇钠的甲醇溶液,在室温下搅拌后放置过夜。加入水,减压蒸去溶剂,再加水。用乙醚提取,往分出的水层中加入饱和氯化钠,放置过夜。冷至0℃过滤,滤饼用小量乙醇洗后,用水溶解,并用稀盐酸酸化至Ph=2。减压蒸除水,20%氯化钠洗,干燥,得类白色的齐多夫定固体,收率89.0%,熔点119.0～122.0℃。

合成制备方法

 胸腺嘧啶脱氧核苷和三苯基膦溶于二甲基甲酰胺中，缓慢滴入对甲氧基苯甲酸和偶氮二甲酸二乙酯(DEAD)溶于二甲基甲酰胺所成的溶液，在室温下搅拌后，再补加三苯基膦和DEAD。搅拌反应后，将反应液倒入乙醚，在0℃下放置过夜。过滤出的固体用小量乙醚洗，干燥，得酯化的氧桥物，收率84.1%。该氧桥物和叠氮钠在二甲基甲酰胺中，于125℃搅拌。冷到室温，将其倒入5%盐酸中，用醋酸乙酯提取。提取液用20%氯化钠溶液洗至中性，干燥，浓缩，真空干燥得叠氮衍生物，收率81.8%。叠氮衍生物和甲醇钠的甲醇溶液，在室温下搅拌后放置过夜。加入水，减压蒸去溶剂，再加水。用乙醚提取，往分出的水层中加入饱和氯化钠，放置过夜。冷至0℃过滤，滤饼用小量乙醇洗后，用水溶解，并用稀盐酸酸化至Ph=2。减压蒸除水，20%氯化钠洗，干燥，得类白色的齐多夫定固体，收率89.0%，熔点119.0～122.0℃。

用途简介

多夫定与其他抗—逆转录病毒药物联合使用，用于治疗人类免疫缺陷性病毒（HIV）感染。

用途

1、   抗病毒药，在细胞内转化为二磷酸酯(DP)和三磷酸酯(TP)的衍生物，从而抑制病毒逆转录酶，阻断病毒DNA的合成，达到抗病毒的目的。用于艾滋病或与艾滋病有关的综合症患者。

2、   用作抗艾滋病和抗病毒药

3、   抗艾滋病和抗病毒原料药。

 

海关代码：

2933990090

WGK_Germany：

3
德国有关水污染物质的分类清单

危险类别码：

R40

安全说明：

S36/37/39-S45

RTECS号：

XP2072000

危险标志：

Xn:Harmful

CHEMICAL IDENTIFICATION

RTECS NUMBER :

XP2072000

CHEMICAL NAME :

Thymidine, 3'-azido-3'-deoxy-

CAS REGISTRY NUMBER :

30516-87-1

LAST UPDATED :

199712

DATA ITEMS CITED :

36

MOLECULAR FORMULA :

C10-H13-N5-O4

MOLECULAR WEIGHT :

267.28

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

1 gm/kg/6W-I

TOXIC EFFECTS :

Skin and Appendages - nails

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

86 mg/kg/1W-I

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - headache

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

434 mg/kg/38D-I

TOXIC EFFECTS :

Blood - changes in cell count (unspecified) Blood - aplastic anemia Blood - changes in bone marrow (not otherwise specified)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

69 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - retinal changes (pigmentary depositions, retinitis, other)

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3084 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity)

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>70 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 :

Unreported

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>750 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 :

3062 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity)

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>70 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 :

Unreported

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>750 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 :

54600 mg/kg/1Y-I

TOXIC EFFECTS :

Blood - pigmented or nucleated red blood cells Blood - changes in erythrocyte (RBC) count

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

91 gm/kg/26W-I

TOXIC EFFECTS :

Blood - normocytic anemia

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

47 gm/kg/94D-I

TOXIC EFFECTS :

Blood - pigmented or nucleated red blood cells Blood - changes in bone marrow (not otherwise specified) Blood - changes in erythrocyte (RBC) count

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

4700 mg/kg/94D-I

TOXIC EFFECTS :

Blood - pigmented or nucleated red blood cells Blood - changes in bone marrow (not otherwise specified) Blood - changes in erythrocyte (RBC) count

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

14500 mg/kg/29D-I

TOXIC EFFECTS :

Blood - pigmented or nucleated red blood cells Blood - changes in erythrocyte (RBC) count Blood - changes in leukocyte (WBC) count

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

6800 mg/kg/17D-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Blood - pigmented or nucleated red blood cells Blood - changes in erythrocyte (RBC) count

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

7 gm/kg/2W-I

TOXIC EFFECTS :

Blood - leukopenia Blood - thrombocytopenia Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

3094 mg/kg/13W-I

TOXIC EFFECTS :

Blood - normocytic anemia

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

18200 mg/kg/26W-I

TOXIC EFFECTS :

Blood - pigmented or nucleated red blood cells Blood - changes in other cell count (unspecified) Blood - changes in erythrocyte (RBC) count

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

12740 mg/kg/1Y-I

TOXIC EFFECTS :

Blood - pigmented or nucleated red blood cells Blood - changes in erythrocyte (RBC) count Blood - changes in platelet count

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

4200 mg/kg

SEX/DURATION :

male 4 week(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands Reproductive - Paternal Effects - other effects on male

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

23 gm/kg

SEX/DURATION :

male 85 day(s) pre-mating female 26 day(s) pre-mating - 3 week(s) post-birth

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)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

69 gm/kg

SEX/DURATION :

male 85 day(s) pre-mating female 26 day(s) pre-mating - 3 week(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Newborn - live birth index (measured after birth)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

27900 mg/kg

SEX/DURATION :

female 26 day(s) pre-mating - 15 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - live birth index (measured after birth)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

910 mg/kg

SEX/DURATION :

female 1-13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) 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 :

6500 mg/kg

SEX/DURATION :

female 6-18 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 :

Micronucleus test

TYPE OF TEST :

Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :

Sister chromatid exchange

TEST SYSTEM :

Rodent - hamster Ovary

DOSE/DURATION :

500 mg/L

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 321,113,1994

生态数据：

若无政府许可，勿将材料排入周围环境。

中国海关编码：2933990090

概述：

2933990090. 其他仅含氮杂原子的杂环化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:20.0%

申报要素：

品名, 成分含量, 用途, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期

摘要/Summary：

2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

计算化学数据

1、   疏水参数计算参考值（XlogP）：0

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：3

6、   拓扑分子极性表面积（TPSA）：93.2

7、   重原子数量：19

8、   表面电荷：0

9、   复杂度：484

10、同位素原子数量：0

11、确定原子立构中心数量：3

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

• 
  3'-叠氮-3'-脱氧胸苷红外图谱(IR1)
• 
  3'-叠氮-3'-脱氧胸苷质谱(MS)