Trimegestone

Base Information

• Chemical Name: Trimegestone
• CAS No.: 74513-62-5
• Molecular Formula: C22H30O3
• Molecular Weight: 342.478
• European Community (EC) Number: 662-727-5
• UNII: 4658K0H08W
• DSSTox Substance ID: DTXSID201317995
• Nikkaji Number: J431.775K
• Wikipedia: Trimegestone
• Wikidata: Q7842164
• NCI Thesaurus Code: C152746
• Metabolomics Workbench ID: 153993
• ChEMBL ID: CHEMBL2104765
• Mol file: 74513-62-5.mol

Synonyms:17-(2-hydroxy-1-oxopropyl)-17-methylestra-4,9-dien-3-one;21-hydroxypromegestone;RU 27987;RU 27988;RU-27987;RU-27988;trimegestone;trimegestone, (17beta(R))-isomer

Chemical Property of Trimegestone

Chemical Property:

• Vapor Pressure: 4.16E-13mmHg at 25°C
• Refractive Index: 1.568
• Boiling Point: 522.6 °C at 760 mmHg
• PKA: 13.04±0.20(Predicted)
• Flash Point: 284 °C
• PSA: 54.37000
• Density: 1.16 g/cm³
• LogP: 4.14860
• XLogP3: 2.6
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 342.21949481
• Heavy Atom Count: 25
• Complexity: 700

Purity/Quality:

98% ^*data from raw suppliers

Trimegestone ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C(=O)C1(CCC2C1(CCC3=C4CCC(=O)C=C4CCC23)C)C)O
• Isomeric SMILES: C[C@@H](C(=O)[C@]1(CC[C@@H]2[C@@]1(CCC3=C4CCC(=O)C=C4CC[C@@H]23)C)C)O
• Recent ClinicalTrials: Study Evaluating Estradiol/Trimegestone in Vasomotor Symptoms (VMS) in Post-Menopausal Women.
• Recent EU Clinical Trials: Characterization of ovulation inhibition of a new vaginal delivery system containing trimegestone - an open-label, single-centre study in healthy females of childbearing potential
• Description: Trimegestone was launched in Sweden in combination with 17 beta-estradiol as hormone replacement therapy (HRT) for the oral treatment of menopausal vasomotor symptoms and the prevention of osteoporosis. Trimegestone can be synthesized in a multistep process starting with 3,3-(ethylenedioxy)estra-5(10),9(11)-dien-17-one and involving a final key regio- and enantioselective reduction of the 17beta-2-oxopropionyl side chain with Saccharomyces cerevisiae in sodium acetate buffer. The norpregnane progestin, trimegestone, exhibited high specificity and affinity for the progesterone receptor, no affinity for the estrogen receptor, and weak affinity for androgen, glucocorticoid and mineralcorticoid receptors. The relative binding affinity of trimegestone for the progestin receptor was 7 times that of progesterone, 4.5 and 1.5 times greater than norethindrone and medroxyprogesterone acetate, respectively. The decrease in circulating estrogen associated with menopause is thought to contribute to a variety of diseases in women, including osteoporosis, cancers, cardiovascular disease, stroke and cognitive dectine. Estrogen conserves bone mass by reducing bone turnover. Estrogen replacement therapy (ERT) is recommended for all women at high risk for osteoporosis. However, estrogen therapy alone has been linked to an increase risk of endometrial cancer; thus progestin (such as trimegestone) is often prescribed in combination with estrogen for women who have not had a hysterectomy. The progestin blocks the estrogenic activity in the endometrium, thereby reducing the potential unwanted cell proliferation in response to estrogen administration. This action of progestin occurs without compromising the beneficial effects of estrogen on hot flashes and bone loss. A study in rats with osteopenia showed that treatment with trimegestone in combination with 17beta-estradiol for 2 months was superior to norethisterone in preventing bone loss. Treatment with trimegestone also more effectively prevented estradiol-induced uterine atrophy as compared to norethisterone. In clinical trials, trimegestone was found to be a highly effective oral progestone for endometrial protection and beneficial effects have been observed on anxiety, depression, somatic, and vasomotor menopausal symptoms. The combination provides improved and predictable cycle control and a better lipid profile in comparison with existing products. Minimal progestogenic adverse events (i.e. mastalgia, acne, nausea, leg cramps, seborrhea and bloatedness) were reported. Totelle Sekvens ? employs a cyclic regimen of 14 days of 2mg of 17beta--estradiol alone and 14 days in combination with 500 μg of trimegestone.
• Uses: Trimegestone causes an increased risk for uterine sarcomas and endometrial cancers with prolonged use. Used in hormone replacement therapies and the treatment of post-menopausal diseases.

Technology Process of Trimegestone

There total 2 articles about Trimegestone which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield:

17α-methyl-17β-(1,2-dioxopropyl)-estra-4,9-dien-3-one → (8S,13S,14S,17S)-17-(1-Hydroxy-2-oxo-propyl)-13,17-dimethyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta[a]phenanthren-3-one + 1-((8S,13S,14S,17S)-3-Hydroxy-13,17-dimethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl)-propane-1,2-dione + trimegestone (74513-62-5) + 17α-methyl-17β-(2-(R)-hydroxy-1-oxopropyl)-estra-4,9-dien-3-one (74525-67-0)

Guidance literature:

With hydrogen; Pt{Sn}0.5*hydrocinchonidine; In ethyl acetate; at 25 ℃; under 60800 Torr; Further Variations:; Catalysts; Temperatures; Pressures; Product distribution;

DOI:10.1006/jcat.1999.2760

Reference yield:

→ trimegestone (74513-62-5)

Guidance literature:

Reference yield: 97.0%

pyridine (110-86-1) + pyridine-SO3 complex (42824-16-8) + trimegestone (74513-62-5) → trimegestone sulfate pyridinium salt (1139685-12-3)

Guidance literature:

at 20 ℃; for 2h;

Downstream raw materials:

trimegestone sulfate pyridinium salt

Refernces

• 1、 -. "Process for the preparation of 20-keto-21 alpha-01-steroids". . . Retrieved 2008/06/13.