298-46-4

• 常用中文名：卡马西平
• 常用英文名：Carbamazepine
• CAS号：298-46-4
• 分子式：C₁₅H₁₂N₂O
• 分子量：236.269
• 相关类别： 原料药 神经系统用药 抗癫痫及抗惊厥药
• 发布时间：2018-04-23 08:00:00
• 更新时间：2024-01-02 11:45:25
• Carbamazepine是压敏钠离子通道阻断剂,IC50为 131 μM。

名称

• 中文名: 卡马西平
• 英文名: carbamazepine
• 中文别名: 卡巴咪嗪; 痛惊宁; 5H-二苯并[b,f]氮杂卓-5-甲酰胺; 立痛定
• 英文别名: Telesmin; Finlepsin; 5H-dibenzob,fazepine-5-carboxamide; 5H-Dibenz(b,f)azepine-5-carboxamide; Neurotol; Calepsin; Carbatrol; Carbelan; EINECS 206-062-7; Carbamazepine; Carbamazepin; 5H-dibenzb,fazepine-5-carboxamide; Timonil; MFCD00005073; 5H-Dibenz[b,f]azepine-5-carboxamide; Tegretol; Biston; Lexin; EPITOL; 5H-Dibenzo[b,f]azepine-5-carboxamide; Sirtal; Stazepine; 5H-DIBENZO(B,F)AZEPINE-5-CARBOXAMIDE

物化性质

• 密度: 1.3±0.1 g/cm3
• 沸点: 411.0±48.0 °C at 760 mmHg
• 熔点: 189-192 °C
• 分子式: C₁₅H₁₂N₂O
• 分子量: 236.269
• 闪点: 202.4±29.6 °C
• 精确质量: 236.094955
• PSA: 46.33000
• LogP: 2.67
• 外观性状: 白色至灰白色粉末
• 蒸汽压: 0.0±1.0 mmHg at 25°C
• 折射率: 1.670
• 储存条件:

  2-8℃储存。

• 水溶解性: pract. insoluble
• 分子结构:

  1、 摩尔折射率：70.08

  2、 摩尔体积（cm³/mol）：193.2

  3、 等张比容（90.2K）：525.8

  4、 表面张力（dyne/cm）：54.7

  5、 极化率（10-24cm3）：27.78

• 计算化学:

  1.疏水参数计算参考值（XlogP）:无

  2.氢键供体数量:1

  3.氢键受体数量:1

  4.可旋转化学键数量:0

  5.互变异构体数量:2

  6.拓扑分子极性表面积46.3

  7.重原子数量:18

  8.表面电荷:0

  9.复杂度:326

  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:

  一、物性数据

  性状：不可用

  密度（g/mL,25/4℃）：白色或类白色结晶性粉末，无臭，无味。

  相对蒸汽密度（g/mL,空气=1）：不可用

  熔点（ºC）：189-192

  沸点（ºC,常压）：不可用

  沸点（ºC,5.2kPa）：不可用

  折射率：不可用

  闪点（ºC）：不可用

  比旋光度（º）：不可用

  自燃点或引燃温度（ºC）：不可用

  蒸气压（kPa,25ºC）：不可用

  饱和蒸气压（kPa,60ºC）：不可用

  燃烧热（KJ/mol）：不可用

  临界温度（ºC）：不可用

  临界压力（KPa）：不可用

  油水（辛醇/水）分配系数的对数值：不可用

  爆炸上限（%,V/V）：不可用

  爆炸下限（%,V/V）：不可用

  溶解性：溶于乙醇、丙酮、丙二醇，不溶于水。

生物活性

• 描述: Carbamazepine是压敏钠离子通道阻断剂,IC50为 131 μM。
• 相关类别:
  信号通路 >> 自噬 >> 自噬
  信号通路 >> 自噬 >> 自噬
  信号通路 >> 跨膜转运 >> 钠通道
  研究领域 >> 神经疾病
• 参考文献:

  [1]. Willow, M. and W.A. Catterall, Inhibition of binding of [3H]batrachotoxinin A 20-alpha-benzoate to sodium channels by the anticonvulsant drugs diphenylhydantoin and carbamazepine. Mol Pharmacol, 1982. 22(3): p. 627-35.

  [2]. Okada, M., et al., Biphasic effects of carbamazepine on the dopaminergic system in rat striatum and hippocampus. Epilepsy Res, 1997. 28(2): p. 143-53.

MSDS

卡马西平 修改号码：5 模块1. 化学品 产品名称： Carbamazepin 修改号码： 5 模块2. 危险性概述 GHS分类 　物理性危害未分类 　健康危害 急性毒性（经口） 第4级 特异性靶器官毒性血液 - 单一接触 [第2级] 　环境危害未分类 GHS标签元素 　图标或危害标志 　信号词警告 　危险描述吞咽有害。 可能因延长或接触对器官产生损害： 血液 　防范说明 [预防]切勿吸入。 使用本产品时切勿吃东西，喝水或吸烟。 处理后要彻底清洗双手。 [急救措施] 食入：若感不适，呼叫解毒中心/医生。漱口。 若感不适：求医/就诊。 [废弃处置] 根据当地政府规定把物品/容器交与工业废弃处理机构。 模块3. 成分/组成信息 单一物质/混和物单一物质 化学名(中文名)：卡马西平 百分比： >97.0%(N) CAS编码： 298-46-4 俗名： 5H-Dibenzo[b,f]azepine-5-carboxamide 卡马西平 修改号码：5 模块3. 成分/组成信息 分子式： C15H12N2O 模块4. 急救措施 吸入： 将受害者移到新鲜空气处，保持呼吸通畅，休息。若感不适请求医/就诊。 皮肤接触： 立即去除/脱掉所有被污染的衣物。用大量肥皂和水轻轻洗。 若皮肤刺激或发生皮疹：求医/就诊。 眼睛接触：用水小心清洗几分钟。如果方便，易操作，摘除隐形眼镜。继续清洗。 如果眼睛刺激：求医/就诊。 食入： 若感不适，呼叫解毒中心/医生。漱口。 紧急救助者的防护：救援者需要穿戴个人防护用品，比如橡胶手套和气密性护目镜。 模块5. 消防措施 合适的灭火剂：干粉，泡沫，雾状水，二氧化碳 特殊危险性：小心，燃烧或高温下可能分解产生毒烟。 特定方法：从上风处灭火，根据周围环境选择合适的灭火方法。 非相关人员应该撤离至安全地方。 周围一旦着火：如果安全，移去可移动容器。 消防员的特殊防护用具：灭火时，一定要穿戴个人防护用品。 模块6. 泄漏应急处理 个人防护措施，防护用具， 使用个人防护用品。远离溢出物/泄露处并处在上风处。 紧急措施：泄露区应该用安全带等圈起来，控制非相关人员进入。 环保措施：防止进入下水道。 控制和清洗的方法和材料：清扫收集粉尘，封入密闭容器。注意切勿分散。附着物或收集物应该立即根据合适的 法律法规处置。 模块7. 操作处置与储存 处理 技术措施：在通风良好处进行处理。穿戴合适的防护用具。防止粉尘扩散。处理后彻底清洗双手 和脸。 注意事项：如果粉尘或浮质产生，使用局部排气。 操作处置注意事项：避免接触皮肤、眼睛和衣物。 贮存 储存条件：保持容器密闭。存放于凉爽、阴暗处。 远离不相容的材料比如氧化剂存放。 包装材料：依据法律。 模块8. 接触控制和个体防护 工程控制：尽可能安装封闭体系或局部排风系统，操作人员切勿直接接触。同时安装淋浴器和洗 眼器。 个人防护用品 　呼吸系统防护：防尘面具。依据当地和政府法规。 　手部防护：防护手套。 　眼睛防护：安全防护镜。如果情况需要，佩戴面具。 　皮肤和身体防护：防护服。如果情况需要，穿戴防护靴。 模块9. 理化特性 外形（20°C）：固体 外观： 晶体-粉末 卡马西平 修改号码：5 模块9. 理化特性 颜色：白色类白色 气味：无资料 pH:无数据资料 熔点： 191°C 沸点/沸程无资料 闪点：无资料 爆炸特性 　爆炸下限：无资料 　爆炸上限：无资料 密度：无资料 溶解度： [水]不溶于 [其他溶剂] 溶于： 甲醇, 丙酮, 氯仿, 二甲基甲酰胺, 丙二醇, 乙二醇单乙醚 微溶于： 乙醇, 冰乙酸 log水分配系数 = 1.98 模块10. 稳定性和反应性 化学稳定性：一般情况下稳定。 危险反应的可能性：未报道特殊反应性。 须避免接触的物质氧化剂 危险的分解产物: 一氧化碳, 二氧化碳, 氮氧化物 (NOx) 模块11. 毒理学信息 急性毒性： orl-rat LD50:1957 mg/kg orl-wmn LDLo:1920 mg/kg/17W-I ipr-rat LD50:158 mg/kg 对皮肤腐蚀或刺激：无资料 对眼睛严重损害或刺激：无资料 生殖细胞变异原性：无资料 致癌性： IARC =无资料 NTP =无资料 生殖毒性：无资料 RTECS 号码: HN8225000 模块12. 生态学信息 生态毒性： 鱼类：无资料 甲壳类：无资料 藻类：无资料 残留性 / 降解性：无资料 潜在生物累积 （BCF):无资料 土壤中移动性 　log水分配系数： 1.98 　土壤吸收系数 （Koc）：无资料 　亨利定律无资料 constant(PaM3/mol): 卡马西平 修改号码：5 模块13. 废弃处置 如果可能，回收处理。请咨询当地管理部门。建议在可燃溶剂中溶解混合，在装有后燃和洗涤装置的化学焚烧炉中 焚烧。废弃处置时请遵守国家、地区和当地的所有法规。 模块14. 运输信息 联合国分类：与联合国分类标准不一致 UN编号：未列明 模块15. 法规信息 《危险化学品安全管理条例》（2002年1月26日国务院发布，2011年2月16日修订）: 针对危险化学品的安全使用、 生产、储存、运输、装卸等方面均作了相应的规定。 模块16 - 其他信息 N/A

毒性和生态

毒理学数据: 二、毒理学数据： 急性毒性：不可用。 生态学数据: 三、生态学数据： 1、其它有害作用：该物质对环境可能有危害，对水体应给予特别注意。 CHEMICAL IDENTIFICATION RTECS NUMBER : HN8225000 CHEMICAL NAME : 5H-Dibenz(b,f)azepine-5-carboxamide CAS REGISTRY NUMBER : 298-46-4 BEILSTEIN REFERENCE NO. : 1246090 LAST UPDATED : 199706 DATA ITEMS CITED : 40 MOLECULAR FORMULA : C15-H12-N2-O MOLECULAR WEIGHT : 236.29 WISWESSER LINE NOTATION : T C676 BNJ BVZ HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 112 mg/kg/2W-I TOXIC EFFECTS : Gastrointestinal - nausea or vomiting Blood - thrombocytopenia REFERENCE : AJPSAO American Journal of Psychiatry. (American Psychiatric Assoc., Circulation Dept., 1400 K St., NW, Washington, DC 20005) V.78- 1921- Volume(issue)/page/year: 150,1750,1993 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - child DOSE/DURATION : 65 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Behavioral - coma Lungs, Thorax, or Respiration - other changes REFERENCE : JOPDAB Journal of Pediatrics. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) V.1- 1932- Volume(issue)/page/year: 121,295,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 144 mg/kg/2W-I TOXIC EFFECTS : Blood - thrombocytopenia Skin and Appendages - dermatitis, allergic (after systemic exposure) REFERENCE : JCLPDE Journal of Clinical Psychiatry. (Physicians Postgraduate Press, Inc., POB 240008, Memphis, TN 38124) V.39- 1978- Volume(issue)/page/year: 53,378,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 160 mg/kg/3W-I TOXIC EFFECTS : Skin and Appendages - dermatitis, other (after systemic exposure) REFERENCE : JCPYDR Journal of Clinical Pyschopharmacology. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1981- Volume(issue)/page/year: 5,185,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - child DOSE/DURATION : 1050 mg/kg/6W-I TOXIC EFFECTS : Behavioral - muscle contraction or spasticity REFERENCE : AJPSAO American Journal of Psychiatry. (American Psychiatric Assoc., Circulation Dept., 1400 K St., NW, Washington, DC 20005) V.78- 1921- Volume(issue)/page/year: 143,1176,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 253 mg/kg/6W-I TOXIC EFFECTS : Gastrointestinal - nausea or vomiting Liver - liver function tests impaired REFERENCE : JCPYDR Journal of Clinical Pyschopharmacology. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1981- Volume(issue)/page/year: 6,251,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - child DOSE/DURATION : 19 mg/kg/4W-I TOXIC EFFECTS : Peripheral Nerve and Sensation - fasciculations REFERENCE : PEDIAU Pediatrics. (American Academy of Pediatrics, P.O. Box 1034, Evanston, IL 60204) V.1- 1948- Volume(issue)/page/year: 73,841,1984 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 28 mg/kg/4D-I TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Gastrointestinal - nausea or vomiting Nutritional and Gross Metabolic - other changes REFERENCE : AJPSAO American Journal of Psychiatry. (American Psychiatric Assoc., Circulation Dept., 1400 K St., NW, Washington, DC 20005) V.78- 1921- Volume(issue)/page/year: 143,1328,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 43 mg/kg TOXIC EFFECTS : Behavioral - sleep Behavioral - hallucinations, distorted perceptions Gastrointestinal - nausea or vomiting REFERENCE : BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 1,754,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 560 mg/kg/4W-I TOXIC EFFECTS : Blood - changes in bone marrow (not otherwise specified) REFERENCE : BJCPAT British Journal of Clinical Practice. (Medical News Group, 1 Bedford St., London WC2E 9HD, UK) V.10(10)- 1956- Volume(issue)/page/year: 43,302,1989 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 54 mg/kg/9D-I TOXIC EFFECTS : Behavioral - ataxia Kidney, Ureter, Bladder - urine volume increased Blood - agranulocytosis REFERENCE : CMAJAX Canadian Medical Association Journal. (Canadian Medical Assoc., POB 8650, Ottawa, ON K1G 0G8, Canada) V.1- 1911- Volume(issue)/page/year: 132,1040,1985 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 1920 mg/kg/17W-I TOXIC EFFECTS : Blood - aplastic anemia REFERENCE : AJPSAO American Journal of Psychiatry. (American Psychiatric Assoc., Circulation Dept., 1400 K St., NW, Washington, DC 20005) V.78- 1921- Volume(issue)/page/year: 142,974,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 94 mg/kg/11D-I TOXIC EFFECTS : Blood - thrombocytopenia REFERENCE : JCPYDR Journal of Clinical Pyschopharmacology. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1981- Volume(issue)/page/year: 10,305,1990 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1957 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) REFERENCE : JKXXAF Japanese Kokai Tokyo Koho Patents. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #79-163823 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 158 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 202,106,1973 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >1500 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,477,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 529 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : FRMCE8 Farmaco. (Societa Chimica Italiana, Corso Strada Nova, 86, Casella Postale 227, 27100 Pavia, Italy) V.44- 1989- Volume(issue)/page/year: 44,595,1989 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 114 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : FATOAO Farmakologiya i Toksikologiya (Moscow). For English translation, see PHTXA6 and RPTOAN. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.2- 1939- Volume(issue)/page/year: 53(4),19,1990 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >1 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,477,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 5620 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,63,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 2680 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,63,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 920 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,63,1972 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 96 mg/kg SEX/DURATION : female 3 week(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System REFERENCE : OBGNAS Obstetrics and Gynecology. (Elsevier Science Pub. Co., Inc., 52 Vanderbilt Ave., New York, NY 10017) V.1- 1953- Volume(issue)/page/year: 82,705,1993 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 3192 mg/kg SEX/DURATION : female 1-38 week(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - delayed effects REFERENCE : NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year: 320,1661,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 7644 mg/kg SEX/DURATION : female 1-39 week(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - skin and skin appendages Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system REFERENCE : NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year: 320,1661,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 1288 mg/kg SEX/DURATION : female 26-42 week(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - skin and skin appendages REFERENCE : NRPDDB Neuropediatrics (Stuttgart). (Hippokrates Verlag GmbH, Postfach 593, D-7000 Stuttgart 1, Fed. Rep. Ger.) V.11- 1980- Volume(issue)/page/year: 16,167,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 3492 mg/kg SEX/DURATION : female 1-39 week(s) after conception lactating female 17 day(s) post-birth TOXIC EFFECTS : Reproductive - Effects on Newborn - biochemical and metabolic REFERENCE : EJPEDT European Journal of Pediatrics. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.121- 1975- Volume(issue)/page/year: 150,136,1990 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 3600 mg/kg SEX/DURATION : female 14 day(s) pre-mating female 1-22 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 29(3),33A,1984 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 765 mg/kg SEX/DURATION : female 9-17 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) Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : EAMJAV East African Medical Journal. (P.O. Box 41632, Nairobi, Kenya) V.9- 1932- Volume(issue)/page/year: 60,407,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 4800 mg/kg SEX/DURATION : female 7-18 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - other developmental abnormalities REFERENCE : TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 41,311,1990 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 7200 mg/kg SEX/DURATION : female 7-18 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 41,311,1990 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 2400 mg/kg SEX/DURATION : female 7-18 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) REFERENCE : TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 41,311,1990 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 440 mg/kg SEX/DURATION : female 6-16 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 40,365,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 92 gm/kg SEX/DURATION : male 2 week(s) pre-mating female 2 week(s) pre-mating - 18 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) 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) REFERENCE : TCMUD8 Teratogenesis, Carcinogenesis, and Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1980- Volume(issue)/page/year: 6,393,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 5628 mg/kg SEX/DURATION : female 7-12 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) REFERENCE : TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 23,33A,1981 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 9984 mg/kg SEX/DURATION : female 8-13 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) REFERENCE : ARNEAS Archives of Neurology (Chicago). (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.3- 1960- Volume(issue)/page/year: 36,832,1979 *** REVIEWS *** TOXICOLOGY REVIEW HFHBAG Hartford Hospital Bulletin. (Hartford Hospital, 80 Seymour St., Hartford, CT 06115) V.1- 1938/39- Volume(issue)/page/year: 30,31,1975 TOXICOLOGY REVIEW EPILAK Epilepsia (New York). (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) Ser.1-3: 1909-55; Ser.4: V.1- 1959- Volume(issue)/page/year: 16,159,1975 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4467 No. of Facilities: 169 (estimated) No. of Industries: 2 No. of Occupations: 5 No. of Employees: 5295 (estimated) No. of Female Employees: 3361 (estimated)

安全

• 符号: GHS07, GHS08
• 信号词: Danger
• 危害声明: H302-H317-H334
• 警示性声明: P261-P280-P342 + P311
• 个人防护装备: dust mask type N95 (US);Eyeshields;Faceshields;Gloves
• 危害码 (欧洲): Xn:Harmful
• 风险声明 (欧洲): R22;R42/43
• 安全声明 (欧洲): S37-S24-S22-S36/37/39
• 危险品运输编码: 3249
• RTECS号: HN8225000
• 包装等级: III
• 危险类别: 6.1(b)
• 海关编码: 2933990090

合成路线

上下游产品

上游产品  10
256-96-2 917-61-3 1189-71-5 42787-75-7
590-28-3 7722-84-1 420-05-3 33948-22-0
506-89-8 59690-99-2
下游产品  9
3564-73-6 42787-75-7 36507-30-9 35079-97-1
52618-28-7 144-62-7 118-92-3 298-12-4
28721-07-5

制备

先由邻硝基甲苯经缩合、还原、环合制得10,11-二氢-5H-二苯并[b,f]氮杂 ，然后经消除、酰化制得该品，或经氯甲酰化、溴化、消除、胺化而得。1.10,11-二氢-5H-二苯并[b,f]氮杂 的制备将甲醇钠和石油醚的混合物冷却，滴加邻硝基甲苯和甲酸乙酯混合液，用稀盐酸调节至pH5-6,2,2'-二硝基联苯。将其溶于乙醇滴加盐酸-乙醇，同时徐徐加入铁粉。用氢氧化钠调至pH8-9过滤，滤液用磷酸调至pH5，析出结晶，得2,2'二氨基联苄磷酸盐。在搅拌下将2,2'二氨基联苄磷酸盐加热至熔融，将物料放入水中析出结晶，得10,11-二氢-5H-二苯并[b,f]氮杂粗品。粗品用石油醚重结晶，得精品。2.卡巴西平的制备方法一将反应床的铁催化剂用热风活化后，控制床温在400-450℃，通入过热蒸汽，慢慢加入熔融的10,11-二氢-5H二苯并[b,f]氮杂，反应产物通过吸收塔用水喷淋吸收，收集塔下浮出的固体，吸滤，干燥得粗品。用乙醇重结晶，得5H二苯并[b,f]氮杂 精品。然后，以苯为溶剂，将5H二苯并[b,f]氮杂 与异氰酸反应再用氢氧化钠溶液调至pH12-14，回流，把温度降至10℃以下，析出结晶，过滤，水洗，干燥，得到卡马西平粗品。粗品用乙醇重结晶、活性炭脱色，即为成品。方法二将10,11-二氢-5H二苯并[b,f]氮杂和甲苯加入反应锅，搅拌加热溶解。回流下通光气，通完后继续回流使氯甲酰化反应完全混合。减压蒸出一部分甲苯，冷却析出结晶，过滤，干燥，得5-氯甲酰基-10,11-二氢二苯并[b,f]氮杂 。将其加入氯苯中，再加入过氧化苯甲酰，加热滴加溴素，加毕，反应至无溴化氢气体逸出为止。将上述反应液趁热转入热乙醇中，通氨，消除、胺化反应结束析出大量固体。蒸除乙醇使反应液呈糊状，加水，过滤，即得粗品。粗品经乙醇重结晶，活性炭脱色，得到卡巴西平成品。

海关

海关编码	2933990090
中文概述	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
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%