Medroxyprogesterone Acetate CAS 71-58-9
Introduction：Basic information about Medroxyprogesterone Acetate CAS 71-58-9, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Medroxyprogesterone Acetate Basic information
| Product Name: | Medroxyprogesterone Acetate |
| Synonyms: | (6-alpha)-17-(acetyloxy)-6-methylpreg-4-ene-3,20-dione;17-(acetyloxy)-6-methyl-(6-alpha)-pregn-4-ene-20-dione;17-(acetyloxy)-6-methyl-20-dion(6alpha)-pregn-4-ene-;17-acetoxy-6-alpha-methylprogesterone;17-alpha-hydroxy-6-alpha-methylpregn-4-ene-3,20-dioneacetate;17-alpha-hydroxy-6-alpha-methyl-progesteronacetate;17-alpha-hydroxy-6-alpha-methylprogesteroneacetate;17-hydroxy-6-alpha-methylpregn-4-ene-3,20-dioneacetate |
| CAS: | 71-58-9 |
| MF: | C24H34O4 |
| MW: | 386.52 |
| EINECS: | 200-757-9 |
| Product Categories: | Antitumors for Research and Experimental Use;Biochemistry;Hydroxyketosteroids;Steroids;PROVERA;API;Hormone Drugs;Intermediates & Fine Chemicals;Pharmaceuticals;Steroid and Hormone;71-58-9 |
| Mol File: | 71-58-9.mol |
Medroxyprogesterone Acetate Chemical Properties
| Melting point | 206-207 °C(lit.) |
| alpha | D +61° (in chloroform) |
| Boiling point | 432.7°C (rough estimate) |
| density | 1.0346 (rough estimate) |
| refractive index | 48 ° (C=1, Dioxane) |
| storage temp. | Sealed in dry,2-8°C |
| solubility | Practically insoluble in water, freely soluble in methylene chloride, soluble in acetone, sparingly soluble in ethanol (96 per cent) |
| form | Solid |
| color | White |
| biological source | synthetic (organic) |
| Water Solubility | <0.1 g/100 mL at 23 ºC |
| Merck | 13,5817 |
| BRN | 2066112 |
| BCS Class | 2,3,1 |
| Stability: | Stable, but weakly air and light sensitive. Incompatible with strong oxidizing agents. |
| InChIKey | PSGAAPLEWMOORI-PEINSRQWSA-N |
| SMILES | [H][C@@]12C[C@H](C)C3=CC(=O)CC[C@]3(C)[C@@]1([H])CC[C@@]4(C)[C@@]2([H])CC[C@]4(OC(C)=O)C(C)=O |
| CAS DataBase Reference | 71-58-9(CAS DataBase Reference) |
| IARC | 2B (Vol. 21, Sup 7) 1987 |
| EPA Substance Registry System | Medroxyprogesterone acetate (71-58-9) |
Safety Information
| Hazard Codes | Xn |
| Risk Statements | 40-48 |
| Safety Statements | 22-36/37/39-45 |
| WGK Germany | 3 |
| RTECS | TU5010000 |
| TSCA | TSCA listed |
| HS Code | 29372390 |
| Storage Class | 11 - Combustible Solids |
| Hazard Classifications | Aquatic Chronic 4 Carc. 2 |
| Description | Medroxyprogesterone Acetate, also known as Medroxyprogesterone 17-acetate or MPA, is a synthetic progestogen and a steroidal progestin. It is derived from the human hormone progesterone. It prevents fertilization and increases the rate of transport of eggs from the fallopian tubes to the uterus in female ferrets when administered prior to ovulation. Medroxyprogesterone 17-acetate reversibly blocks ovulation in rats when injected on the last day of diestrus. It also has anti-androgenic activity in rats, decreasing plasma testosterone levels via induction of hepatic testosterone reductase activity. Medroxyprogesterone 17-acetate exhibits immunosuppressive effects in vitro and in vivo, inhibiting the production of IFN-γ by CD2/CD3/CD28-stimulated peripheral blood mononuclear cells (PBMCs) at concentrations ≥10 nM and extending the survival of rabbit skin allografts. Injectable formulations containing medroxyprogesterone 17-acetate have been used as contraceptives. |
| Chemical Properties | White or almost white, crystalline powder. |
| Originator | Provera,Upjohn,US,1959 |
| Uses | Medroxyprogesterone Acetate is a synthetic progesterone receptor agonist that is used to treat amenorrhea (unusual stopping of menstrual periods) and abnormal uterine bleeding. |
| Definition | ChEBI: Medroxyprogesterone acetate is an acetate ester resulting from the formal condensation of the 17alpha-hydroxy group of medroxyprogesterone with the carboxy group of acetic acid. A widely used progestin in menopausal hormone therapy and in progestogen-only birth control. It has a role as a progestin, an androgen, a female contraceptive drug, a synthetic oral contraceptive, an adjuvant, an inhibitor, an antioxidant and an antineoplastic agent. It is a steroid ester, an acetate ester, a 20-oxo steroid, a 3-oxo-Delta(4) steroid and a corticosteroid. It is functionally related to a medroxyprogesterone. |
| Brand name | Amen (Amarin);Curretab (Solvay Pharmaceuticals); Cycrin (ESI); Provera(Pharmacia & Upjohn);Clinovie;Cliovir;Dep0-clinover;Dep0-map;Depcorlutin;Depo-prodasone;Depo-progevera;Depo-promone;Deporone;Dugen;Farlurin;Farlutale;Gesinal;Gestapuran;Gestapuron;G-farlutal;Hysron;Intex;Luteocrin orale;Luteodione;Luteos;Lutoporal;Metigestene;Nadigest;Nogest;Onco-provera;Perlutest;Petogen;Piermap;Povera;Promone-e;Pronone;Proverone;Provest;Sindomens;Sodelut "g";Supprestal;Verafen;Veramix plus v. |
| Therapeutic Function | Progestin |
| World Health Organization (WHO) | A depot preparation containing 150 mg medroxyprogesteroneacetate was introduced over 20 years ago for use as a long-acting injectablecontraceptive. Subsequently, positive results of carcinogenicity studies carried outin beagle bitches led to refusal of registration in the United States. These findingswere later considered irrelevant to contraceptive use in women and the drug wasapproved by the Food and Drug Administration. Menstrual irregularities are themost common adverse effect associated with depot medroxyprogesterone acetate.Risk-benefit judgements differ significantly from country to country, having regardto differing national circumstances. The preparation is, however, widely availableand is included in the WHO Model List of Essential Drugs.(Reference: (WHTAC4) The Use of Essential Drugs, 4th Report of the WHO ExpertCommittee, 796, , 1990) |
| General Description | Medroxyprogesterone acetate is an odorless white to off-white microcrystalline powder. It is a synthetic, acetate derivative of the sex hormone progesterone. (NTP, 1992) |
| Air & Water Reactions | Medroxyprogesterone 17-acetate is sensitive to prolonged exposure to air and light. Insoluble in water. |
| Reactivity Profile | Flammable and/or toxic gases are generated by the combination of alcohols with alkali metals, nitrides, and strong reducing agents. They react with oxoacids and carboxylic acids to form esters plus water. Oxidizing agents convert them to aldehydes or ketones. Alcohols exhibit both weak acid and weak base behavior. They may initiate the polymerization of isocyanates and epoxides. |
| Hazard | Possible carcinogen. |
| Fire Hazard | Flash point data for Medroxyprogesterone 17-acetate are not available; however, Medroxyprogesterone 17-acetate is probably combustible. |
| Biochem/physiol Actions | Medroxyprogesterone 17-acetate (MPA) is a synthetic progestin used as a contraceptive, in hormone replacement therapy and for the treatment of endometriosis. It is a more potent progestin that the nonacetylated form. |
| Clinical Use | Progestogen: Cachexia (unlicensed), contraception, epilepsy, male hypersexuality, malignant neoplasms, respiratory disorders, sickle-cell disease, dysfunctional uterine bleeding, endometriosis |
| Safety Profile | Suspected carcinogen with experimental carcinogenic, neoplastigenic, tumorigenic, and teratogenic data. Human systemic effects by intravenous route: increased intraocular pressure. Human teratogenic effects by an unspecified route: developmental abnormalities of the urogenital system. Human reproductive effects by multiple routes: spermatogenesis, menstrual cycle changes or dlsorders, postpartum effects, female fertility effects, abortion, newborn behavioral effects. Human mutation data reported. Experimental reproductive effects. A drug for the treatment of secondary amenorrhoea and dysfunctional uterine bleeding. When heated to decomposition it emits acrid smoke and irritating fumes. |
| Synthesis | 32634-95-0 71-58-9 S1: To a 500 mL three-necked flask was added 40 g of 6-methylenepregna-4-en-17α-ol-3,20-dione-17-acetate, 400 mL of ethanol, 30 g of cyclohexene and 2.5 g of 5% palladium-carbon catalyst. The reaction mixture was heated to 75-78 °C and maintained for 5 hours. The reaction process was monitored by HPLC. Upon completion of the reaction, the reaction mixture was filtered to recover the palladium-carbon catalyst.S2: After the reaction solution was cooled to below 50 °C, 14 mL of hydrochloric acid was slowly added and the reaction temperature was controlled between 40-50 °C for 3 hours. At the end of the reaction, the pH of the reaction solution was adjusted with saturated sodium bicarbonate solution to 6-7. Subsequently, the reaction solution was concentrated to a paste under reduced pressure and the temperature inside the flask was lowered to below 20 °C. The reaction solution was then dried to a solid of 0.5 mL. The resulting solid was filtered, washed and dried to give 28.5 g of crude product.S3: The crude product was recrystallized using a solvent mixture of methanol and dichloromethane to give 35 g of pure product with a total yield of 87.5% and an impurity F content of 0.35%. |
| Veterinary Drugs and Treatments | In cats, MPA has been used when either castration is ineffective orundesirable to treat sexually dimorphic behavior problems such asroaming, inter-male aggressive behaviors, spraying, mounting, etc.MPA has also been used as a tranquilizing agent to treat syndromessuch as feline psychogenic dermatitis and alopecia, but treatmentwith “true” tranquilizing agents may be preferable. In humans, parenteral MPA has been used as a long-actingcontraceptive in females, to decrease sexually deviant behavior inmales, and as an antineoplastic agent for some carcinomas (seePharmacology section above). Oral MPA is used in human femalesto treat secondary amenorrhea and to treat abnormal uterine bleedingsecondary to hormone imbalances. |
| Metabolism | Among the first of these substituted 17α-acetoxyprogesterone analogues to be utilized therapeutically was medroxyprogesteroneacetate, a 6α-methyl progesterone analogue. This analogue is 25-fold more active than ethisterone. Following oraladministration, medroxyprogesterone acetate is completely and rapidly deacetylated by first-pass metabolism tomedroxyprogesterone. Medroxyprogesterone is extensively metabolized via pathways similar to those for progesterone, except for6α-hydroxylation. Most medroxyprogesterone acetate metabolites are excreted in the urine, primarily as glucuronide conjugates.Plasma protein binding for medroxyprogesterone is approximately 86%, primarily to serum albumin, with no binding to SHBG. |
| References | 1. Chang, M.C. Effects of medroxyprogesterone acetate and of ethinyl oestradiol on the fertilization and transportation of ferret eggs. J. Reprod. Fertil. 13(1), 173-174 (1967). DOI:10.1530/JRF.0.0130173 2. Dickmann, Z. Short-and long-term effects of a single injection of depo-medroxyprogesterone acetate (provera) on the vaginal smear, ovulation and mating in the rat. J. Reprod. Fertil. 32(3), 447-451 (1973). DOI:10.1530/JRF.0.0320447 3. Albin, J., Vittek, J., Gordon, G.G., et al. On the mechanism of the anti-androgenic effect of medroxyprogesterone acetate. Endocrinology 93(2), (1973). DOI:10.1210/ENDO-93-2-417 4. Huijbregts, R.P., Michel, K.G., and Hel, Z. Effect of progestins on immunity: Medroxyprogesterone but not norethisterone or levonorgestrel suppresses the function of T cells and pDCs. Contraception 90(2), 123-129 (2014). DOI:10.1016/j.contraception.2014.02.006 5. Turcotte, J.G., Haines, R.F., Brody, G.L., et al. Immunosuppression with medroxyprogesterone acetate. Transplantation 6(2), 248-260 (1968). DOI:10.1097/00007890-196803000-00010 6. Hofmeyr, G.J., Singata-Madliki, M., Lawrie, T.A., et al. Effects of the copper intrauterine device versus injectable progestin contraception on pregnancy rates and method discontinuation among women attending termination of pregnancy services in South Africa: A pragmatic randomized controlled trial. Reprod. Health 13, 42 (2016). DOI:10.1186/s12978-016-0153-9 7. Thomas CP, Liu KZ, Vats HS. Medroxyprogesterone acetate binds the glucocorticoid receptor to stimulate alpha-ENaC and sgk1 expression in renal collecting duct epithelia. Am J Physiol Renal Physiol. 2006 Feb;290(2):F306-12. Epub 2005 Sep 27. DOI:10.1152/AJPRENAL.00062.2005 8. Braden BB, Talboom JS, Crain ID, Simard AR, Lukas RJ, Prokai L, Scheldrup MR, Bowman BL, Bimonte-Nelson HA. Medroxyprogesterone acetate impairs memory and alters the GABAergic system in aged surgically menopausal rats. Neurobiol Learn Mem. 2010Mar;93(3):444-53. DOI:10.1016/j.nlm.2010.01.002 |
Medroxyprogesterone Acetate Preparation Products And Raw materials
| Raw materials | Sulfuric acid-->Ethylene glycol-->Peroxyacetic acid-->Methylmagnesium Bromide-->Acetic anhydride-->17-hydroxy-6-methylenepregn-4-ene-3,20-dione 17-acetate-->Ethanol-->Cyclohexene-->Palladium hydroxide |
| Preparation Products | MEDROXYPROGESTERONE-->17-(Acetyloxy)-6α-methyl-5β-pregnane-3,20-dione |
