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孕三烯酮

孕三烯酮用途

Gestrinone (R2323) 是用于治疗子宫内膜异位症的合成类固醇激素。抑制平滑肌瘤的IC50值为43.67 μM。

孕三烯酮名称

[ CAS 号 ]:
16320-04-0

[ 中文名 ]:
孕三烯酮

[ 英文名 ]:
Gestrinone

[中文别名 ]:

[英文别名 ]:

D-GESTRINONE
Dimetriose
TridoMose
Dimetrose
MFCD00865561
gestrigone
Gestrinone
NeMestran

孕三烯酮生物活性

[ 描述 ]:

Gestrinone (R2323) 是用于治疗子宫内膜异位症的合成类固醇激素。抑制平滑肌瘤的IC50值为43.67 μM。

[ 相关类别 ]:

信号通路 >> 其他 >> 雌激素受体/ERR

研究领域 >> 炎症/免疫

[ 靶点 ]

IC50: 43.67 μM (leiomyoma cells)[2]

[体外研究]

尽管存在内源性类固醇,但雌甾酮与雌激素,黄体酮和雄激素的子宫内膜受体结合,占据类固醇靶细胞中类固醇的所有特异性结合位点[1]。雌激素对60小时的平滑肌瘤细胞生长的抑制作用强于20小时和40小时。平滑肌瘤细胞看起来密度较小,细胞质萎缩,细胞间连接减少,超过10μM孕三烯酮治疗时观察到核聚集。在浓度为0.1-3.0μM时,雌甾酮治疗以浓度依赖性方式降低雌激素α的相对mRNA水平[2]。

[体内研究]

通过用氟他胺和达那唑或孕三烯酮的组合治疗,增强了雌激素敏感终点,阴道角化和子宫孕酮受体浓度。这些数据表明,达那唑和孕三烯酮具有雌激素活性,这些活性被这些药物的雄激素成分所掩盖[3]。用一周治疗后,用孕三烯酮处理的平均激素结合球蛋白从56.4nM下降到28.1nM,在4周后分别下降到7.1nM [4]。

[细胞实验]

将雌甾酮溶解在DMSO中并在细胞培养基中稀释。培养基中DMSO的最终浓度为0.5％。将细胞在96孔板中培养，并用DMSO或分级浓度的孕三烯酮（0.1,0.5,1.0,5.0,10,50或100μM）处理20,40和60小时。读取450nm处的吸光度（OD）以确定每个孔中的细胞活力[2]。

[参考文献]

[1]. Tamaya T, et al. Gestrinone (R2323) binding to steroid receptors in human uterine endometrial cytosol. Acta Obstet Gynecol Scand. 1986;65(5):439-41.

[2]. Zhu Y, et al. Gestrinone inhibits growth of human uterine leiomyoma may relate to activity regulation of ERα, Src and P38 MAPK. Biomed Pharmacother. 2012 Dec;66(8):569-77.

[3]. Snyder BW, et al. Studies on the mechanism of action of danazol and gestrinone (R2323) in the rat: evidence for a masked estrogen component. Fertil Steril. 1989 Apr;51(4):705-10.

[4]. Dowsett M, et al. A comparison of the effects of danazol and gestrinone on testosterone binding to sex hormone binding globulin in vitro and in vivo. Clin Endocrinol (Oxf). 1986 May;24(5):555-63.

[相关活性小分子]

孕三烯酮物理化学性质

[ 密度 ]:
1.2±0.1 g/cm3

[ 沸点 ]:
507.6±50.0 °C at 760 mmHg

[ 熔点 ]:
154ºC

[ 分子式 ]:
C₂₁H₂₄O₂

[ 分子量 ]:
308.414

[ 闪点 ]:
214.9±22.7 °C

[ 精确质量 ]:
308.177643

[ PSA ]:
37.30000

[ LogP ]:
3.27

[ 外观性状 ]:
淡黄色固体

[ 蒸汽压 ]:
0.0±3.0 mmHg at 25°C

[ 折射率 ]:
1.607

[ 储存条件 ]:
-20°C Freezer

孕三烯酮毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: JF7964000

CHEMICAL NAME :: 18,19-Dinor-17-alpha-pregna-4,9,11-trien-20-yn-3-one, 13-ethyl-17-hydroxy-

CAS REGISTRY NUMBER :: 16320-04-0

LAST UPDATED :: 199612

DATA ITEMS CITED :: 13

MOLECULAR FORMULA :: C21-H24-O2

MOLECULAR WEIGHT :: 308.45

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1 gm/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Skin and Appendages - dermatitis, other (after systemic exposure) Nutritional and Gross Metabolic - other changes

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 16,701,1988

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1 gm/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - visual field changes Behavioral - altered sleep time (including change in righting reflex) Nutritional and Gross Metabolic - other changes

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 16,701,1988

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1 gm/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Gastrointestinal - other changes

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 16,701,1988 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 400 ug/kg

SEX/DURATION :: female 8 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - menstrual cycle changes or disorders Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 14,275,1976

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1200 ug/kg

SEX/DURATION :: female 12 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - menstrual cycle changes or disorders

REFERENCE :: FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 31,278,1979

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Implant

DOSE :: 1800 ug/kg

SEX/DURATION :: female 48 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - menstrual cycle changes or disorders Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 11,625,1975

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravaginal

DOSE :: 185 ug/kg

SEX/DURATION :: female 28 day(s) pre-mating

TOXIC EFFECTS :: 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: 14,671,1976

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravaginal

DOSE :: 2600 ug/kg

SEX/DURATION :: female 26 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - menstrual cycle changes or disorders

REFERENCE :: FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 49,418,1988

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 50 mg/kg

SEX/DURATION :: female 6-15 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 - Effects on Embryo or Fetus - fetal death

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 16,713,1988

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 500 ug/kg

SEX/DURATION :: female 6-15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 16,713,1988

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 20 mg/kg

SEX/DURATION :: female 15-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 16,737,1988

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1200 mg/kg

SEX/DURATION :: female 15-18 day(s) after conception lactating female 20 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 16,737,1988

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Implant

DOSE :: 2486 ug/kg

SEX/DURATION :: female 1 year(s) pre-mating

TOXIC EFFECTS :: 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: 15,335,1977

孕三烯酮上下游产品

孕三烯酮上游产品

孕三烯酮下游产品

孕三烯酮制备

【方法一】
方法1：化合物(Ⅰ)和化合物(Ⅱ)经Robinson环合，得双环化物(Ⅲ)。还原后再苯甲酰化，得到(Ⅳ)。部分水解后，用醋酐处理，得烯醇内酯(V)。和化合物(Ⅵ)的格氏试剂反应后，再水解得到三环化物(Ⅶ)。在四氢吡咯作用下，环合得(Ⅷ)。水解得(Ⅸ)，用二氯二氢醌(DDQ)脱氢，引入最后一个双键得(X)。水解脱去苯甲酰基成醇，再氧化得3，17-二酮(Ⅺ)。在酸存在下和乙二醇反应得3-缩酮(Ⅻ)。和乙炔溴化镁反应，引入乙炔基，再脱去保护基得到孕三烯酮。
方法2：把化合物(ⅩⅣ)加入2.5ml乙酸、2.5ml水和0.25ml丙酮酸的溶液中，在氮气气氛中加热回流lh。冷却，倾入冰水中。加入过量的碳酸氢钠，用乙醚提取。提取液水洗至中性，真空蒸馏至于，得65mg粗品。该粗品溶入二氯甲烷，用硅酸镁层析，洗脱液为二氯甲烷，得51mg产品。先用乙酸乙酯，再用苯一环己烷(1：1)混合液重结晶，得36mg的孕三烯酮，熔点154℃。