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84371-65-3 分子结构
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(10S,11S,14S,15S,17R)-17-[4-(dimethylamino)phenyl]-14-hydroxy-15-methyl-14-(prop-1-yn-1-yl)tetracyclo[8.7.0.02,7.011,15]heptadeca-1,6-dien-5-one

ChemBase编号:713
分子式:C29H35NO2
平均质量:429.5937
单一同位素质量:429.26677937
SMILES和InChIs

SMILES:
O[C@@]1([C@@]2([C@H]([C@H]3C(=C4C(=CC(=O)CC4)CC3)[C@H](C2)c2ccc(N(C)C)cc2)CC1)C)C#CC
Canonical SMILES:
CC#C[C@]1(O)CC[C@@H]2[C@]1(C)C[C@H](c1ccc(cc1)N(C)C)C1=C3CCC(=O)C=C3CC[C@@H]21
InChI:
InChI=1S/C29H35NO2/c1-5-15-29(32)16-14-26-24-12-8-20-17-22(31)11-13-23(20)27(24)25(18-28(26,29)2)19-6-9-21(10-7-19)30(3)4/h6-7,9-10,17,24-26,32H,8,11-14,16,18H2,1-4H3/t24-,25+,26-,28-,29-/m0/s1
InChIKey:
VKHAHZOOUSRJNA-GCNJZUOMSA-N

引用这个纪录

CBID:713 http://www.chembase.cn/molecule-713.html

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名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
(10S,11S,14S,15S,17R)-17-[4-(dimethylamino)phenyl]-14-hydroxy-15-methyl-14-(prop-1-yn-1-yl)tetracyclo[8.7.0.02,7.011,15]heptadeca-1,6-dien-5-one
(10S,11S,14S,15S,17R)-17-[4-(dimethylamino)phenyl]-14-hydroxy-15-methyl-14-(prop-1-yn-1-yl)tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-1,6-dien-5-one
IUPAC传统名
mifepristone
商标名
Mifegyne
Mifeprex
Corlux
别名
11β-(4-Dimethyl-amino)-phenyl-17β-hydroxy-17-(1-propynyl)-estra-4,9-dien-3-one
Mifepristone
RU486
Mifepristona [Spanish]
Mifepristonum [Latin]
Mifepriston
mifepristone
Mifepristone
RU-486
RU-38486
Mifegyne
Mifepristone(Mifeprex)
(11β,17β)-11-[4-(Dimethylamino)phenyl]-17-hydroxy-17-(1-propyn-1-yl)estra-4,9-dien-3-one
Mifeprex
Mifestone
VGX 410
CAS号
84371-65-3
MDL号
MFCD00867226
PubChem SID
160964176
46505795
24278572
PubChem CID
55245

数据来源

数据来源

所有数据来源 商品来源 非商品来源

理论计算性质

理论计算性质

JChem ALOGPS 2.1
Acid pKa 12.865694  质子受体
质子供体 LogD (pH = 5.5) 5.038118 
LogD (pH = 7.4) 5.1319485  Log P 5.1332874 
摩尔折射率 132.5809 cm3 极化性 50.040565 Å3
极化表面积 40.54 Å2 可自由旋转的化学键
里宾斯基五规则 false 
Log P 5.33  LOG S -5.11 
溶解度 3.36e-03 g/l 

分子性质

分子性质

理化性质 安全信息 药理学性质 产品相关信息 生物活性(PubChem)
溶解度
Chloroform expand 查看数据来源
Poorly soluble [FDA Label] expand 查看数据来源
外观
Pale Yellow Solid expand 查看数据来源
熔点
195-198°C expand 查看数据来源
疏水性(logP)
4.5 expand 查看数据来源
保存条件
-20°C expand 查看数据来源
-20°C Freezer expand 查看数据来源
RTECS编号
KG2955000 expand 查看数据来源
欧盟危险性物质标志
有毒(Toxic) 有毒(Toxic) (T) expand 查看数据来源
MSDS下载
下载链接 expand 查看数据来源
德国WGK号
3 expand 查看数据来源
危险公开号
60-61 expand 查看数据来源
安全公开号
53-22-36/37/39-45 expand 查看数据来源
GHS危险品标识
GHS08 expand 查看数据来源
GHS警示词
Danger expand 查看数据来源
GHS危险声明
H360 expand 查看数据来源
GHS警示性声明
P201-P308 + P313 expand 查看数据来源
个人保护装置
Eyeshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges expand 查看数据来源
保存温度
2-8°C expand 查看数据来源
相关基因信息
human ... AR(367), ESR1(2099), ESR2(2100), HTR1A(3350), HTR1B(3351), HTR1D(3352), HTR1E(3354), HTR1F(3355), HTR2A(3356), HTR2B(3357), HTR2C(3358), HTR3A(3359), HTR3B(9177), HTR3C(170572), HTR3D(200909), HTR3E(285242), HTR4(3360), HTR5A(3361), HTR5B(645694), HTR6(3362), HTR7(3363), NR3C1(2908), NR3C2(4306), PGR(5241)mouse ... Nr3c1(14815)rat ... Nr3c1(24413), Tat(24813) expand 查看数据来源
纯度
≥98% expand 查看数据来源
成盐信息
Free Base expand 查看数据来源
质检报告
下载链接 expand 查看数据来源

详细说明

详细说明

DrugBank DrugBank Selleck Chemicals Selleck Chemicals Sigma Aldrich Sigma Aldrich TRC TRC
DrugBank -  DB00834 external link
Item Information
Drug Groups approved; investigational
Description A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary cushing syndrome. [PubChem]
Indication For the medical termination of intrauterine pregnancy through 49 days' pregnancy. Also indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance.
Pharmacology Mifepristone is a synthetic steroid with antiprogestational effects indicated for the medical termination of intrauterine pregnancy through 49 days' pregnancy. Doses of 1 mg/kg or greater of mifepristone have been shown to antagonize the endometrial and myometrial effects of progesterone in women. During pregnancy, the compound sensitizes the myometrium to the contraction-inducing activity of prostaglandins. Mifepristone also exhibits antiglucocorticoid and weak antiandrogenic activity. The activity of the glucocorticoid dexamethasone in rats was inhibited following doses of 10 to 25 mg/kg of mifepristone. Doses of 4.5 mg/kg or greater in human beings resulted in a compensatory elevation of adrenocorticotropic hormone (ACTH) and cortisol.
Toxicity Nearly all of the women who receive mifepristone will report adverse reactions, and many can be expected to report more than one such reaction. About 90% of patients report adverse reactions following administration of misoprostol on day three of the treatment procedure. Side effects include more heavy bleeding than a heavy manstrual period, abdominal pain, uterine cramping, nausea, vomiting, and diarrhea.
Affected Organisms
Humans and other mammals
Biotransformation Hepatic. Hepatic, by Cytochrome P450 3A4 isoenzyme to the N-monodemethylated metabolite (RU 42 633); RU 42 698, which results from the loss of two methyl groups from position 11 beta; and RU 42 698, which results from terminal hydroxylation of the 17–propynyl chain.
Absorption The absolute bioavailability of a 20 mg oral dose is 69%
Half Life 18 hours
Protein Binding 98% (bound to plasma proteins, albumin and a 1-acid glycoprotein)
Elimination Fecal: 83%; Renal: 9%.
References
Fiala C, Gemzel-Danielsson K: Review of medical abortion using mifepristone in combination with a prostaglandin analogue. Contraception. 2006 Jul;74(1):66-86. Epub 2006 May 19. [Pubmed]
Heikinheimo O, Kekkonen R, Lahteenmaki P: The pharmacokinetics of mifepristone in humans reveal insights into differential mechanisms of antiprogestin action. Contraception. 2003 Dec;68(6):421-6. [Pubmed]
Chabbert-Buffet N, Meduri G, Bouchard P, Spitz IM: Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications. Hum Reprod Update. 2005 May-Jun;11(3):293-307. Epub 2005 Mar 24. [Pubmed]
Spitz IM, Bardin CW, Benton L, Robbins A: Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med. 1998 Apr 30;338(18):1241-7. [Pubmed]
Piaggio G, von Hertzen H, Heng Z, Bilian X, Cheng L: Meta-analyses of randomized trials comparing different doses of mifepristone in emergency contraception. Contraception. 2003 Dec;68(6):447-52. [Pubmed]
External Links
Wikipedia
RxList
Drugs.com
Selleck Chemicals -  S2606 external link
Research Area
Description Endocrinology
Biological Activity
Description Mifepristone (Mifeprex, RU-486, RU-38486, Mifegyne) is a remarkably active antagonist of progesterone receptor and glucocorticoid receptor with IC50 of 0.2 nM and 2.6 nM, respectively.
Targets Progesterone receptor Glucocorticoid receptor
IC50 0.2 nM 2.6 nM [1]
In Vitro Mifepristone inhibit corticoid-induced transcription from a glucocorticoid response element (GRE)-linked luciferase reporter gene in the human lung carcinoma cell line A549. Moreover, Mifepristone also blocks progesterone induction of alkaline phosphatase activity in the human breast cancer cell line T47D. [1] Mifepristone inhibits ovarian cancer cell growth of SK-OV-3 and OV2008 with IC50 of 6.25 μM and 6.91 μM, respectively. [2] A recent study shows that Mifepristone induces caspase-1 over expression both in differentiated and undifferentiated caspase-1-embryonic stem cells. [3]
In Vivo Mifepristone can impair the growth of SK-OV-3 tumors in immunosuppressed mice at 0.5 mg/day and 1 mg/day. [2] Mifepristone inhibits the prostate weight significantly in the highest doses in vivo, and inhibits growth of the prostate gland produced by dihydrotestosterone (DHT) to a greater extent than the induction of atrophy and cell death in rats. [4]
Clinical Trials Mifepristone is currently in Phase III clinical trial in patients with depressive disorder.
Features Mifepristone is the first approved medication for patients with wndogenous cushing’s syndrome.
Protocol
Kinase Assay [1]
Glucocorticoid receptor (GR) antagonist activity, Progesterone receptor (PR) antagonist activity T47D alkaline phosphatase assay: T47D human breast cancer cells are plated in 96-well tissue culture plates at 104 cells per well in assay medium [RPMI medium without phenol red containing 5% (v/v) charcoal-treated FBS and 1% (v/v) penicillin–streptomycin]. Two days later, the medium is decanted and Mifepristone or control is added at a final concentration of 0.1% (v/v) dimethylsulfoxide in fresh assay medium. Twenty-four hours later, an alkaline phosphatase assay is performed using a SEAP kit. The medium is decanted and the cells are fixed for 30 minutes at room temperature with 5% (v/v) formalin. The cells are washed once at room temperature with Hanks’ buffered saline solution. Equal volumes (0.05 mL) of dilution buffer, assay buffer, and 1:20 substrate/enhancer mixture are then added. After 1-hour incubation in the dark at room temperature, the lysate is transferred to a white 96-well plate and luminescence is read using a LuminoSkan Ascen. A549 reporter assay: A549 human lung carcinoma cells are washed with OPTI-MEM I. The medium was removed and lipid–DNA complex solution (1.5 μg/mL of GRE-luciferase reporter DNA in 8.5 mL OPTI-MEM I plus 6 μL/mL DMRIE-C reagent in 8.5 mL OPTI-MEM I, combined, mixed and incubated at room temperature for 40 minutes) is overlayed onto the cells in a T160 flask. The cells are incubated for 16 hours at 37 °C in a CO2 incubator. The DNA-containing medium is removed and 30 mL of growth medium containing 5% (v/v) charcoal-treated fetal bovine serum is added. After 5-6 hours, the cells are seeded in 96-well plates and incubated overnight at 37 °C. Mifepristone is then added to each well followed by dexamethasone as a corticoid challenge. The cells are incubated for 24 hours. Luciferase assay buffer is added to each well and the cells are incubated for 30 minutes at room temperature. Luciferase activity is measured in a DYNEX Microlite plate on a TopCount.
Cell Assay [2]
Cell Lines OV2008 and SK-OV-3 cells
Concentrations 0-20 μM
Incubation Time 24 hours
Methods Cell growth is evaluated in various ovarian cancer cell lines that are subjected to dose-response or time course treatments. Media containing each of the doses of fresh steroids is replaced every 24 hours. Control groups of cells are treated with vehicle ethanol at a final concentration of less than 0.05%. Number of viable cells is evaluated by trypsinization and counting in a hemocytometer chamber using trypan blue dye exclusion. Experiments are conducted in media without phenol red and supplemented with charcoal extracted fetal bovine serum, or media containing unextracted serum and having phenol red. Similar results are obtained with both media preparations; therefore, after performing the growth curves, all subsequent experiments are conducted using media with unextracted serum and in the presence of phenol red. When indicated, the proliferation IC50s are calculated using software designed to study drug interaction.
Animal Study [2]
Animal Models SK-OV-3 ovarian cancer cells are injected into immunosuppressed mice.
Formulation Constant release pellets (Innovative Research of America)
Doses 0.5 or 1 mg/day
Administration Implanted s.c. with pellets
References
[1] Jiang W, et al. Bioorg Med Chem, 2006, 14(19), 6726-6732.
[2] Goyeneche AA, et al. Clin Cancer Res, 2007, 13(11), 3370-3379.
[3] Wang Y, et al. Stem Cells, 2012, 30(2), 169-179.
[4] Cabeza M, et al. J Steroid Biochem Mol Biol, 2007, 104(3-5), 321-325.
Sigma Aldrich -  M8046 external link
Frequently Asked Questions
Live Chat and Frequently Asked Questions are available for this Product.
Biochem/physiol Actions
Mifepristone (RU-486) has activity as both a progesterone receptor antagonist and a glucocorticoid receptor antagonist.
Toronto Research Chemicals -  M343975 external link
A progesterone receptor antagonist with partial agonist activity. Abortifacient.

参考文献

参考文献

供应商提供 Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • Fiala C, Gemzel-Danielsson K: Review of medical abortion using mifepristone in combination with a prostaglandin analogue. Contraception. 2006 Jul;74(1):66-86. Epub 2006 May 19. Pubmed
  • Heikinheimo O, Kekkonen R, Lahteenmaki P: The pharmacokinetics of mifepristone in humans reveal insights into differential mechanisms of antiprogestin action. Contraception. 2003 Dec;68(6):421-6. Pubmed
  • Chabbert-Buffet N, Meduri G, Bouchard P, Spitz IM: Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications. Hum Reprod Update. 2005 May-Jun;11(3):293-307. Epub 2005 Mar 24. Pubmed
  • Spitz IM, Bardin CW, Benton L, Robbins A: Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med. 1998 Apr 30;338(18):1241-7. Pubmed
  • Piaggio G, von Hertzen H, Heng Z, Bilian X, Cheng L: Meta-analyses of randomized trials comparing different doses of mifepristone in emergency contraception. Contraception. 2003 Dec;68(6):447-52. Pubmed
  • Jiang W, et al. Bioorg Med Chem, 2006, 14(19), 6726-6732.
  • Goyeneche AA, et al. Clin Cancer Res, 2007, 13(11), 3370-3379.
  • Wang Y, et al. Stem Cells, 2012, 30(2), 169-179.
  • Cabeza M, et al. J Steroid Biochem Mol Biol, 2007, 104(3-5), 321-325.
  • Healy, D.L., et al.: J. Clin. Endocrinol. Metab., 57, 863 (1983)
  • Rauch, M., et al.: Eur. J. Biochem., 148, 213 (1983)
  • Baulieu, E.E., et al.: Science, 245, 1351 (1983)
  • Brogden, R.N., et al.: Drugs, 45, 384 (1993)
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专利

专利

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