Mifepristone

In 1980, Mifepristone (CAS NO.84371-65-3) was discovered by researchers at Roussel Uclaf of France while they were studying glucocorticoid receptor antagonists.étienne-émile Baulieu recognized its anti-progesterone activities and saw its potential for the induction of a medical abortion. Clinical testing began in 1982. The drug was first licensed in France in 1988, for use in combination with a prostaglandin, under the name Mifegyne. After license approval but before market release, Roussel Uclaf announced it would abandon distribution of the drug, bowing to pressure from pro-life groups and the threat of a boycott. However, two days later, the French government, part owner of Roussel Uclaf, intervened, leading to the resumption of production and distribution of RU-486.

1. Introduction of Mifepristone
Mifepristone is one kind of pale yellow solid. The IUPAC Name of this chemical is (8S,11R,13S,14S,17S)-11-[4-(dimethylamino)phenyl]-17-hydroxy-13-methyl-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one. Mifepristone belongs to Steroids;Hormone;Acetylenes;Biochemistry;Functionalized Acetylenes;Hydroxyketosteroids;Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;Intracellular receptor;Nuclear Receptors. Mifepristone is soluble in organic solvents but poorly soluble in water.

The Classification Code of this chemical is Abortifacient Agents; Abortifacient agents, steroidal; Contraception; Contraceptive Agents; Contraceptive Agents, Female; Contraceptives, Oral; Contraceptives, Postcoital; Contraceptives, oral, synthetic; Contraceptives, postcoital, synthetic; Hormone; Hormone antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Human Data; Induction of abortion; Luteolytic agents; Menstruation-inducing agents; Reproductive Control Agents; Reproductive Effect; Treatment of gynecological disorders [progesterone antagonist].

2. Properties of Mifepristone
Physical properties about Mifepristone are:
(1)Index of Refraction: 1.623; (2)Molar Refractivity: 127.71 cm³; (3)Molar Volume: 362 cm³; (4)Polarizability: 50.62×10^-24 cm³; (5)Surface Tension: 54 dyne/cm; (6)Density: 1.18 g/cm³; (7)Flash Point: 334 °C; (8)Enthalpy of Vaporization: 97.77 kJ/mol; (9)Melting Point: 195-198°C; (10)Boiling Point: 628.6 °C at 760 mmHg; (11)Vapour Pressure: 1.14E-16 mmHg at 25°C; (12)XLogP3-AA: 3.8; (13)H-Bond Donor: 1; (14)H-Bond Acceptor: 3.

3. Structure Descriptors of Mifepristone
(1)Canonical SMILES: CC#CC1(CCC2C1(CC(C3=C4CCC(=O)C=C4CCC23)C5=CC=C(C=C5)N(C)C)C)O
(2)InChIKey: VKHAHZOOUSRJNA-GCNJZUOMSA-N
(3)Isomeric SMILES: CC#C[C@@]1(CC[C@@H]2[C@@]1(C[C@@H](C3=C4CCC(=O)C=C4CC[C@@H]23)C5=CC=C(C=C5)N(C)C)C)O
(4)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
(5)Smiles: C1=2[C@H]([C@H]3[C@]([C@@](C#CC)(O)CC3)(C)C[C@@H]1c1ccc(N(C)C)cc1)CCC=1C2CCC(C1)=O

4. Safety information of Mifepristone
Hazard Codes: T
Risk Statements: 60-61 
S60:This material and its container must be disposed of as hazardous waste. 
S61:Avoid release to the environment. Refer to special instructions / safety data sheets.
Safety Statements: 53-22-36/37/39-45 
S53:Avoid exposure - obtain special instructions before use. 
S22:Do not breathe dust. 
S36/37/39:Wear suitable protective clothing, gloves and eye/face protection. 
S45:In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.)
WGK Germany: 3
RTECS: KG2955000

5. Uses of Mifepristone
Mifepristone (CAS NO.84371-65-3) is a synthetic steroid compound used as a pharmaceutical. It is used as an abortifacient in the first two months of pregnancy, and in smaller doses as an emergency contraceptive. Other medical applications of mifepristone that have been studied in Phase II clinical trials include regular long-term use as an oral contraceptive, and treatment of: uterine fibroids, endometriosis, major depression with psychotic features, glaucoma, meningiomas, breast cancer, ovarian cancer, prostate cancer, and some types of Cushing's syndrome.

6. Production of Mifepristone
(1)Steroidal 4,9 estrogen diene-3 ,17-dione 3 ketal compound (I) as raw material and propynyl magnesium bromide Grignard reagent, at 17 for introduction of the propargyl group, to obtain the compound (II). Followed by five ethylenically for selective epoxidation to give compound (III). Containing copper bromide - dimethyl sulfide complex in tetrahydrofuran, and dimethylaminophenyl magnesium bromide in 11 introduces dimethylaminophenyl to give the compound (IV). Finally, in methanol, by hydrolysis with hydrochloric acid and dehydrated to obtain a mifepristone. Yield is 21.5%.



(2) Another way to get the Mifepristone is showed as follows: