Mifepristone CAS 84371-65-3
Introduction：Basic information about Mifepristone CAS 84371-65-3, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Mifepristone Basic informationDescription
| Product Name: | Mifepristone |
| Synonyms: | ra-4,9-dien-3-one;ru486-6;MIFEGYNE;MIFEPRISTONE;RU-38486;RU486;11BETA-[4-(DIMETHYLAMINO)PHENYL]-17BETA-HYDROXY-17-(1-PROPYNYL)ESTRA-4,9-DIEN-3-ONE;(11BETA,17BETA)-11-(4-(DIMETHYLAMINO)PHENYL)-17-HYDROXY-17-(1-PROPYNYL)ESTRA-4,9-DIEN-3-ONE |
| CAS: | 84371-65-3 |
| MF: | C29H35NO2 |
| MW: | 429.59 |
| EINECS: | 617-559-7 |
| Product Categories: | Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;Intracellular receptor;Steroids;Hormone;Acetylenes;Biochemistry;Functionalized Acetylenes;Hydroxyketosteroids;Nuclear Receptors;Hormone Drugs;API;Steroid and Hormone;84371-65-3 |
| Mol File: | 84371-65-3.mol |
Mifepristone Chemical Properties
| Melting point | 195-198°C |
| alpha | D20 +138.5° (c = 0.5 in chloroform) |
| Boiling point | 544.13°C (rough estimate) |
| density | 1.0731 (rough estimate) |
| refractive index | 1.6290 (estimate) |
| storage temp. | 2-8°C |
| solubility | Soluble in DMSO (up to 40 mg/ml) or in Ethanol (up to 20 mg/ml). |
| pka | 12.94±0.60(Predicted) |
| form | Yellow solid |
| color | Yellow |
| biological source | synthetic (organic) |
| Water Solubility | 474.8ug/L(22.5 ºC) |
| Merck | 14,6186 |
| Stability: | Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months. |
| InChIKey | VKHAHZOOUSRJNA-GCNJZUOMSA-N |
| SMILES | [H][C@@]12CCC3=CC(=O)CCC3=C1[C@H](C[C@@]4(C)[C@@]2([H])CC[C@@]4(O)C#CC)c5ccc(cc5)N(C)C |
| CAS DataBase Reference | 84371-65-3(CAS DataBase Reference) |
Safety Information
| Hazard Codes | T |
| Risk Statements | 60-61 |
| Safety Statements | 53-22-36/37/39-45 |
| WGK Germany | 3 |
| RTECS | KG2955000 |
| HS Code | 29372900 |
| Storage Class | 6.1C - Combustible acute toxic Cat.3 toxic compounds or compounds which causing chronic effects |
| Hazard Classifications | Repr. 1B |
| Hazardous Substances Data | 84371-65-3(Hazardous Substances Data) |
| Description | Mifepristone is a kind of antagonist of the progestational and glucocorticoid hormone. It is mainly used for the treatment of hypercortisolism in patients with nonpituitary cushing syndrome. During the treatment of Cushing’s syndrome, mifepristone takes effect through interfering with the binding of cortisol to its receptor. It reduces the effects of excess cortisol (e.g., high blood sugar levels) without causing decreased cortisol production. It can also be used to end a pregnancy. Its inhibition on progesterone can induce bleeding during the luteal phase and in early pregnancy. |
| Description | Mifepristone is an orally-active progesterone and glucocorticoid receptor antagonistindicated for use as a post-coital contraceptive. In addition to being an abortifacient,mifepristone is reported to be effective in the treatment of ocular hypertension; itspotential therapeutic effect in hormone-dependent tumors is currently under investigation. |
| Chemical Properties | Pale Yellow Solid |
| Originator | Roussel-Uclaf (France) |
| History | Mifepristone (brand name: Mifeprex) is an abortion drug approved by the FDA in 2000 for the medical termination of pregnancy, up to 7 weeks of gestation, an extension extended to 10 weeks in 2016. A generic version of Mifeprex, mifepristone tablets (200 mg), was approved in 2019. The drug has been in use for 25 years. However, following a study by the Center for Ethics and Public Policy (EPPC) showing that nearly 11% of women using the drug experience serious adverse events, the FDA is reviewing the safety of mifepristone. |
| Uses | A progesterone receptor antagonist with partial agonist activity. Abortifacient. |
| Uses | glutamate uptake inhibitor, AMPA blocker |
| Uses | A progesterone and glucocorticoid antagonist, suppresses VEGF production. |
| Uses | Mifepristone is a progesterone receptor antagonist with partial agonist activity. Abortifacient. |
| Definition | ChEBI: Mifepristone is a 3-oxo-Delta(4) steroid, an acetylenic compound and a tertiary amino compound. It has a role as an abortifacient, a contraceptive drug, a synthetic oral contraceptive and a hormone antagonist. It derives from a hydride of an estrane. |
| Indications | Mifepristone is a progesterone receptor antagonist thathas a high affinity for glucocorticoid receptors and littleagonist effect.This drug has recently been approved foruse in the United States for the treatment of hypercortisolism.At high doses, mifepristone blocks negativefeedback of the hypothalamic–pituitary axis, thereby increasingendogenous corticotrophin and cortisol levels.Because mifepristone exerts its effects at the receptorlevel and not by altering glucocorticoid production, elevatedserum cortisol and corticotrophin levels may notaccurately reflect the effectiveness of the therapeuticregimen. Mifepristone does not inhibit cortisol bindingto the mineralocorticoid receptor, so that the resultingcorticotrophin disinhibition may cause potassium depletion.Thus, administration of a mineralocorticoid receptorantagonist such as spironolactone may be indicatedwith mifepristone. Hypoadrenalism, nausea, anddrowsiness have been reported during prolonged administrationof mifepristone. |
| Manufacturing Process | 1st method of synthesis of mifepristone:A solution of 24 g of 4-(N,N-dimethylaminoethoxy)bromobenzene was addeddropwise over 45 min to magnesium in 90 ml of anhydrous tetrahydrofuran. 2ml of 1,2-dibromoethane were added as catalyst. After the addition, themixture was stirred at 25°C for one hour to obtain a solution of 0.7 M of 4-(N,N-dimethylaminoethoxy)-benzene magnesium bromide which was thenadded to a solution of 6.16 g of dimethylsulfide-cuprous bromide complex in20 ml of tetrahydrofuran. The mixture was stirred at room temperature for 20min and a solution of 3.7 g of 3,3-[1,2-(ethanediyl-bisoxy)]-5α,10α-epoxy-17α-prop-1-ynyl-δ(9(11))-estrene-17β-ol in 50 ml of tetrahydrofuran was addedthereto dropwise over a few minutes. The mixture was stirred under an inertatmosphere for one hour and was then poured into a solution of 15 g ofammonium chloride in 20 ml of iced water. The mixture was extracted withether and the organic phase was washed with aqueous saturated sodiumchloride solution, was dried and evaporated to dryness under reducedpressure. The 18.3 g of oil were chromatographed over silica gel and elutedwith chloroform to obtain 4.5 g of 3,3-[1,2-ethanediyl-bisoxy]-11β-[4-(N,N-dimethylaminoethoxy)phenyl]-17α-(prop-1-ynyl)-δ9-estrene-5α,17β-diol with aspecific rotation of [α]D20=-44(+/-)1.5° (c = 1% in chloroform). 9.5 ml of 2 N hydrochloric acid were added to a solution of 4.5 g of 3,3-[1,2-ethanediyl-bisoxy]-11β-[4-(N,N-dimethylaminoethoxy)phenyl]-17α-(prop-1-ynyl)-δ9-estrene-5α,17β-diol in 20 ml of methanol and the solution was stirredat room temperature for 2 hours. 260 ml of ether and 110 ml of an aqueoussaturated sodium bicarbonate solution were added to the mixture which wasstirred at room temperature for 15 min. The decanted aqueous phase wasextracted with ether and the organic phase was dried and evaporated todryness under reduced pressure. The 3.3 g of residue were chromatographedover silica gel and eluted with a 92.5/7.5 methylene chloride-methanolmixture to obtain 1.8 g of amorphous 11β-[4-(N,N-dimethylaminoethoxy)phenyl]-17α-(prop-1-ynyl)-δ4,9-estradiene-17β-ol-3-one with a specificrotation of [α]D20=+71° (c = 1% in chloroform). 2th method of synthesis of mifepristone (see scheme):The oxidation of the diene I, which constitutes an intermediate for totalsynthesis of 19-nor steroids, with a reagent prepared from trifluoroaceticanhydride/hydrogen peroxide was obtained exclusively α-epoxide II. Thecondensation of II with the Grignard reagent from 4-bromo-N,N-dimethylaniline results in addition of the reagent at the 11β-position. Thisresults in rearragement of the olefin to 9,10 and opening of the epoxide. Thestereochemistry of the product obtained III is consistent with trans-opening ofthe oxirane, albeit at a remove of two carbon atoms. Mild hydrolysis removesthe silyl cyanohydrin protecting group at the 17-position to give a ketone IV.Reaction of the ketone with propargyl lithium leads to V. Hydrolysis of thatproduct under more strenuous condition results in removal of the acetal at 3;the resulting β-hydroxyketone then dehydrates to afford the 4,10(9)-dienoneVI. Another name of VI is estra-4,9-dien-3-one, 11-(4-(dimethylamino)phenyl)-17-hydroxy-17-(1-propynyl)-, (11β,17β)- or mifepristone. |
| Brand name | Mifeprex (Danco);Ru-486;Mifegyne. |
| Therapeutic Function | Antiprogesterone |
| World Health Organization (WHO) | Mifepristone, an antiprogesterone used in combination with aprostaglandin for the termination of early pregnancy, was introduced in 1990. Useof the combination has been associated with episodes of coronary spasm that areattributed to administration of the prostaglandin and which have resulted in severalcases of cardiac infarction and ventricular fibrillation. At least one of theseincidents has been fatal. |
| Biological Activity | Selective antagonist at progesterone (PR) and glucocorticoid (GR) receptors in vitro and in vivo . Is a silent antagonist at PR and has a higher affinity than progesterone. Has higher affinity for GR than dexamethasone. |
| Biochem/physiol Actions | Therefore, mifepristone is considered to be a potent abortifacient. It is also known to inhibit human chorionic gonadotropin. Mifepristone results in decidual necrosis. |
| Pharmacokinetics | Following oral administration, mifepristone is rapidly absorbed, with a peak plasmaconcentration in approximately 90 minutes , an oral bioavailability of approximately 70%, and a term inal elimination half-life of 18 hours. It is 98% protein bound, primarily to album in and α1-acid glycoprotein. Mifepristone is metabolized primarily via CYP3A4 pathways involving mono- and di-N-demethylation and terminal hydroxylation of the 17-propynyl chain. The fact that approximately 83% of the drug is recovered in the feces and 9% in the urine suggests a biliary route of elimination. Mifepristone also demonstrates antiglucocorticoid activity. |
| Clinical Use | An antiprogestin is a substance that competes with progesterone for its receptor and, ultimately, prevents progesterone from binding to and activating its receptor. Because progesterone is integral to the continuation of an early pregnancy, it is expected that antipro-gestins will interfere with pregnancy maintenance. In 1982, the first antiproges tin, mifepristone (RU 486), was reported. Mifepristone was shown to interrupt early stages of implantation and pregnancy in humans. |
| storage | Room temperature |
| References | https://pubchem.ncbi.nlm.nih.gov/compound/mifepristone#section=Top https://www.drugbank.ca/drugs/DB00834 https://www.drugs.com/cdi/mifepristone-tablets.html |
Mifepristone Preparation Products And Raw materials
| Raw materials | Tetrahydrofuran-->N,N-Dimethylaniline-->Diisopropyl ether-->Dimethyl sulfide-->1,2-Dibromoethane |
