6533-00-2

• 常用中文名：炔诺孕酮
• 常用英文名：Levonorgestrel
• CAS号：6533-00-2
• 分子式：C₂₁H₂₈O₂
• 分子量：312.446
• 相关类别： 原料药 激素及调节内分泌功能类药 避孕药
• 发布时间：2018-03-31 08:00:00
• 更新时间：2024-01-02 12:47:12
• Norgestrel 是孕酮的合成类似物,是口服避孕药中常见的化合物,也是一种强大的神经保护性抗氧化剂,可防止光诱导的感光细胞中的 ROS 的生成以及细胞死亡。

名称

• 中文名: 炔诺孕酮
• 英文名: levonorgestrel
• 中文别名: DL-甲基炔诺酮; 18-甲基炔诺酮; 高诺酮
• 英文别名: (8R,9S,10R,13S,14S,17R)-13-Ethyl-17-ethynyl-17-hydroxy-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one; Mirena; 13-Ethyl-17-ethynyl-17b-hydroxy-4-gonen-3-one; 17a-Ethynyl-18-homo-19-nortestosterone; Norgeston; 13b-Ethyl-17a-ethynyl-17b-hydroxygon-4-en-3-one; 18-METHYLNORETHINDRONE; 18-Methyl-17a-ethynyl-19-nortestosterone; (−)-Norgestrel; Norplant; (17a)-13-Ethyl-17-hydroxy-18,19-dinorpregn-4-en-20-yn-3-one; Levonelle; 13-β-ETHYL-17-α-ETHYNYL-17-β-HYDROXYGON-4-EN-3-ONE; monovar; MFCD01546387; sh850; wy3707; 17b-Hydroxy-18-methyl-19-nor-17a-pregn-4-en-20-yn-3-one; (8R,9S,10R,13S,14S,17R)-17-Ethinyl-13-ethyl-17-hydroxy-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-on; Levonova; (8R,9S,10R,13S,14S,17R)-13-éthyl-17-éthynyl-17-hydroxy-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tétradécahydro-3H-cyclopenta[a]phénanthrén-3-one; 17a-Ethynyl-18-methyl-19-nortestosterone; EINECS 212-349-8; 17a-Ethynyl-17-hydroxy-18-methylestr-4-en-3-one; D-Norgestrel; Microval; 13-Ethyl-17-hydroxy-18,19-dinor-17a-pregn-4-en-20-yn-3-one; Norgestrel; 17a-Ethynyl-13-ethyl-19-nortestosterone; Microlut; Ovrette; UNII:3J8Q1747Z2; D(−)-Norgestrel; NorLevo; (17a)-(-)-13-Ethyl-17-hydroxy-18,19-dinorpregn-4-en-20-yn-3-one; D-(-)-Norgestrel; Neogest; (-)-Norgestrel; 13-Ethyl-17a-ethynyl-17-hydroxygon-4-en-3-one; fh122-a

物化性质

• 密度: 1.1±0.1 g/cm3
• 沸点: 459.1±45.0 °C at 760 mmHg
• 熔点: 239-241ºC
• 分子式: C₂₁H₂₈O₂
• 分子量: 312.446
• 闪点: 195.4±21.3 °C
• 精确质量: 312.208923
• PSA: 37.30000
• LogP: 3.92
• 外观性状: 白色结晶粉末
• 蒸汽压: 0.0±2.6 mmHg at 25°C
• 折射率: 1.571
• 储存条件: 2-8°C

生物活性

• 描述: Norgestrel 是孕酮的合成类似物,是口服避孕药中常见的化合物,也是一种强大的神经保护性抗氧化剂,可防止光诱导的感光细胞中的 ROS 的生成以及细胞死亡。
• 相关类别:
  研究领域 >> 癌症
• 体外研究: Norgestrel(20μM；24小时；661W细胞)处理显着增加血清剥夺后的细胞活力,因此证明Norgestrel对应激的661W细胞具有神经保护作用[1]。Norgestrel(20μM；24小时；661W细胞)处理减少细胞凋亡诱导的PARP和caspase-3裂解[1]。Norgestrel(20μM；6小时；661W细胞)处理bFGF导致光感受器细胞中bFGF mRNA的显着上调[1]。细胞活力测定[1]细胞系：661W细胞浓度：20μM孵育时间：24小时结果：血清剥夺后细胞活力显着增加。蛋白质印迹分析[1]细胞系：661W细胞浓度：20μM孵育时间：24小时结果：凋亡诱导的PARP和caspase-3裂解减少。RT-PCR[1]细胞系：661W细胞浓度：20μM孵育时间：6小时结果：1小时内bFGF mRNA显着上调。
• 体内研究: Norgestrel(100mg/kg；腹膜内注射；6,24或48小时；Balb/c小鼠)治疗可以预防光感受器细胞中光诱导的ROS,以及随后的细胞死亡。Norgestrel通过主要抗氧化转录因子Nrf2的翻译后调节起作用；引起其磷酸化,随后的核转位,并增加其效应蛋白超氧化物歧化酶2(SOD2)的水平[2]。动物模型：Balb/c小鼠出生并维持在昏暗的循环光中[2]剂量：100 mg/kg；给药：腹腔注射；6,24或48小时结果：通过丝氨酸40磷酸化增加Nrf2的表达和活化,增加其靶抗氧化剂超氧化物歧化酶2(SOD2)的表达,并减少线粒体氧化应激。
• 参考文献:

  [1]. Wyse Jackson AC, et al. The synthetic progesterone Norgestrel is neuroprotective in stressed photoreceptor-like cellsand retinal explants, mediating its effects via basic fibroblast growth factor, protein kinase A and glycogen synthase kinase 3β signalling. Eur J Neurosci. 2016 Apr;43(7):899-911.

  [2]. Byrne AM, et al. The synthetic progestin norgestrel modulates Nrf2 signaling and acts as an antioxidant in a model of retinal degeneration. Redox Biol. 2016 Dec;10:128-139.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : JF8225200 CHEMICAL NAME : 18,19-Dinor-17-alpha-pregn-4-en-20-yn-3-one, 13-ethyl-17-hydroxy-, (+-)- CAS REGISTRY NUMBER : 6533-00-2 LAST UPDATED : 199109 DATA ITEMS CITED : 27 MOLECULAR FORMULA : C21-H28-O2 MOLECULAR WEIGHT : 312.49 WISWESSER LINE NOTATION : L E5 B666 OV MUTJ E2 FQ F1UU1 -DL 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 : 5010 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 18,185,1971 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 11200 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Liver - other changes REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 29,1479,1978 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >10 gm/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Liver - other changes REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 29,1479,1978 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 5010 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 18,185,1971 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 7300 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Liver - other changes REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 29,1479,1978 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >9 gm/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Liver - other changes REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 29,1479,1978 ** TUMORIGENIC DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 57 mg/kg/68W-C TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Skin and Appendages - tumors REFERENCE : CRSBAW Comptes Rendus des Seances de la Societe de Biologie et de Ses Filiales. (SPPIF, B.P.22, F-41353 Vineuil, France) V.1- 1849- Volume(issue)/page/year: 168,1190,1974 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 18 ug/kg SEX/DURATION : female 12 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - ovaries, fallopian tubes REFERENCE : FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 23,739,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 4 mg/kg SEX/DURATION : female 40 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated) REFERENCE : INJFA3 International Journal of Fertility. (Allen Press, 1041 New Hampshire, St., Lawrence, KS 66044) V.1- 1955- Volume(issue)/page/year: 11,401,1966 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 365 ug/kg SEX/DURATION : female 52 week(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated) REFERENCE : BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 2,730,1969 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 75 ug/kg SEX/DURATION : female 5 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - menstrual cycle changes or disorders Reproductive - Fertility - other measures of fertility REFERENCE : CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 12,589,1975 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 30 ug/kg SEX/DURATION : female 30 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated) REFERENCE : BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 4,489,1968 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 150 mg/kg SEX/DURATION : female 15-24 day(s) after conception TOXIC EFFECTS : Reproductive - Maternal Effects - parturition REFERENCE : PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 123,867,1966 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 525 mg/kg SEX/DURATION : female 35 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated) REFERENCE : INJFA3 International Journal of Fertility. (Allen Press, 1041 New Hampshire, St., Lawrence, KS 66044) V.1- 1955- Volume(issue)/page/year: 11,389,1966 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 548 ug/kg SEX/DURATION : female 49 week(s) pre-mating female 1-22 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) REFERENCE : CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 2,59,1970 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 210 mg/kg SEX/DURATION : female 14 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - uterus, cervix, vagina REFERENCE : FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 24,284,1973 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 5 mg/kg SEX/DURATION : female 15-24 day(s) after conception TOXIC EFFECTS : Reproductive - Maternal Effects - parturition REFERENCE : PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 123,867,1966 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 60 mg/kg SEX/DURATION : female 17-20 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - urogenital system REFERENCE : AVBIB9 Advances in the Biosciences. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1967- Volume(issue)/page/year: 13,71,1974 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 700 ug/kg SEX/DURATION : female 14 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Fertility - other measures of fertility REFERENCE : CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 5,57,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 140 mg/kg SEX/DURATION : female 14 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - uterus, cervix, vagina REFERENCE : CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 5,57,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular DOSE : 12 mg/kg SEX/DURATION : male 30 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands REFERENCE : IJEBA6 Indian Journal of Experimental Biology. (Publications & Information Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963- Volume(issue)/page/year: 10,159,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular DOSE : 19200 ug/kg SEX/DURATION : male 48 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females) REFERENCE : IJEBA6 Indian Journal of Experimental Biology. (Publications & Information Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963- Volume(issue)/page/year: 10,159,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Implant DOSE : 6 mg/kg SEX/DURATION : female 17 week(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) REFERENCE : CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 12,549,1975 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular DOSE : 33 mg/kg SEX/DURATION : male 94 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - other effects on male REFERENCE : IJEBA6 Indian Journal of Experimental Biology. (Publications & Information Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963- Volume(issue)/page/year: 7,49,1969 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 180 ug/kg SEX/DURATION : female 30 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - uterus, cervix, vagina Reproductive - Maternal Effects - other effects REFERENCE : IJMRAQ Indian Journal of Medical Research. (Indian Council of Medical Research, Ansari Nagar, New Delhi 110 029, India) V.1- 1913- Volume(issue)/page/year: 63,1413,1975 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Implant DOSE : 600 ug/kg SEX/DURATION : female 17 week(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) REFERENCE : CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 12,549,1975 *** REVIEWS *** TOXICOLOGY REVIEW JIMRBV Journal of International Medical Research. (Cambridge Medical Pub. Ltd., 435/437 Wellingborough Rd., Northampton, NN1 4EZ, UK) V.1- 1972- Volume(issue)/page/year: 1,141,1973

安全

• 危害码 (欧洲): Xn:Harmful
• 风险声明 (欧洲): R20/21/22;R40
• 安全声明 (欧洲): S22-S36
• 危险品运输编码: NONH for all modes of transport
• WGK德国: 3
• RTECS号: JF8259000