1162-60-3

Basic information

• Product Name: -4-TIBOLONE
• Synonyms: (7R,17R)-17-Hydroxy-7-methyl-19-norpregn-4-en-20-yn-3-one;7α-Methyl-17β-hydroxy-17-ethynylestra-4-ene-3-one;Org OD 14 4-ene isomer;(7α,17α)-17-Hydroxy-7-Methyl-19-norpregn-4-en-20-yn-3-one;17α-Ethynyl-17 -hydroxy-7α-Methyl-4-estren-3-one;Gestrinone Impurity 8;-4-TIBOLONE;(7a,17a)-17-Hydroxy-7-methyl-19-norpregn-4-en-20-yn-3-one
• CAS NO: 1162-60-3
• Molecular Formula: C₂₁H₂₈O₂
• Molecular Weight: 312.45
• Product Categories: Steroids;Various Metabolites and Impurities;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals
• Mol File: 1162-60-3.mol

Chemical Properties

• Melting Point: 165-169°C
• Boiling Point: 452.5°Cat760mmHg
• Flash Point: 192.7°C
• Appearance: /
• Density: 1.13g/cm³
• Vapor Pressure: 4.32E-10mmHg at 25°C
• Refractive Index: 1.569
• Storage Temp.: -20°C Freezer
• PKA: 13.10±0.60(Predicted)
• CAS DataBase Reference: -4-TIBOLONE(CAS DataBase Reference)
• NIST Chemistry Reference: -4-TIBOLONE(1162-60-3)
• EPA Substance Registry System: -4-TIBOLONE(1162-60-3)

Safety Data

• Hazardous Substances Data: 1162-60-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
-4-TIBOLONE is used as a pharmaceutical agent for the treatment of menopausal syndrome. Its unique combination of weak estrogenic, androgenic, and progestogenic activities helps alleviate the symptoms associated with menopause, providing relief and improving the quality of life for women experiencing this condition.

InChI:InChI=1/C21H28O2/c1-4-21(23)10-8-18-19-13(2)11-14-12-15(22)5-6-16(14)17(19)7-9-20(18,21)3/h1,12-13,16-19,23H,5-11H2,2-3H3

Upstream product

• 3764-87-2 7α-methyl-19-nortestosterone 
• 107-21-1 ethylene glycol 
• 70277-75-7 lithium acetylide 
• 105186-33-2 3,3-dimethoxy-7α-methyl-19-nor-17α-pregn-5(10)-en-20-yn-17β-ol 
• 105186-32-1 7α-methylestr-5(10)-ene-3,17-dione 
• 88247-84-1 3,3-dimethoxy-7α-methylestr-5(10)-en-17-one 
• 63841-74-7 7α-methyl-3,17-dioxoandrost-4-en-19-al 
• 677299-58-0 7α-methylnorethynodrel ethylene ketal 
• 5630-53-5 tibolone 
• 917-64-6 methyl magnesium iodide 
• 676-58-4 methylmagnesium chloride 
• 75-16-1 methylmagnesium bromide 

Downstream Products

• 677299-58-0 7α-methylnorethynodrel ethylene ketal 
• 5630-53-5 tibolone 
• 105186-33-2 3,3-dimethoxy-7α-methyl-19-nor-17α-pregn-5(10)-en-20-yn-17β-ol 

Relevant articles and documents

7α-Methy-17α-(E-2′[ 125l]iodvinyl)-19-nortestosterone: A new radioligand for the detection of androgen receptor

We have synthesized two γ-emitting, 125I-labeled steroids, E- and Z-7α-methyl-17α-((2′-[ 125I]iodovinyl)-19-nortestosterone [125I](E- and Z-MIVNT) for specific labeling of androgen receptors. [125I]E- and [125I]Z-MIVNTwere synthesized stereospecifically from E- and Z-7α-methyl- 17α-(2′-tri-n-butylstannylvinyl)-19-nortestosterone. The tin adducts were prepared by addition of tri-n-butyltin hydride to 7α-methyl-17α-ethynyl-19-nortestosterone, and after purification they were converted in high yield to the [125I]MIVNT isomers by reaction with 125I (generated in situ by oxidation of [125I] iodide with chloramine T). The 125I-labeledproducts were purified by high-performance liquid chromatography, and their mass determined with an ultraviolet detector (specific activity of both, approximately 2,200 Ci/mmol). In rat prostate cytosol, [125I]E-MIVNT bound with high affinity to a single class of binding sites. Nonspecific binding in the presence of 5α-dihydrotestosterone was relatively low, and compared favorably with that obtained in parallel studies with [3H]methyltrienolone (R1881). The E-isomer bound prostate cytosol with at least twice the affinity of the Z-isomer; therefore, the interaction of the E-isomer with the androgen receptor as well as other steroid receptors was studied in greater detail. Complexes of the androgen receptor with [125I]E-MIVNT as well as [3H]R1881 dissociate very slowly at 4C (kdiss for BOTH = 0.04 h-1). Displacement studies showed that the interaction of[125I]E-MIVNTwith the androgen receptor is highly specific. Competition studies showed that unlabeled E-MIVNT binds poorly to other steroid receptors in rat tissue cytosols. These binding properties make [125I]E-MIVNT a promising ligand for study of the androgen receptor, and [1325I]E-MIVNT a potential imaging agent for the detection of androgen-dependent tumors, such as prostate cancer. (Steroids 58:13-23, 1993).

COMPOUNDS FOR TARGETED THERAPIES OF CASTRATION RESISTANT PROSTATE CANCER

The present invention generally relates to new compounds for therapeutic uses. In particular, this disclosure relates to novel tetracyclic compounds useful for treatment of cancer, especially castration resistant prostate cancer. Pharmaceutical composition matters and methods for treating a cancer patient by administering therapeutically effective amounts of such compound alone or together with other therapeutics are within the scope of this disclosure.

Preparation method of tibolone

The invention discloses a preparation method of tibolone, and belongs to the technical field of preparation and processing of steroid hormone drugs. According to the method, 6,7-didehydronorethindroneis used as an initial raw material, and tibolone is prepared through Grignard reaction, dietherification reaction and hydrolysis reaction. The 7-methyl introduction step is included in the Grignard reaction step in the synthesis route, so that special protection on 17-site hydroxyl is avoided, and the ratio of the 7-alpha methyl intermediate to the 7-beta methyl isomer obtained through the reaction is larger than 20:1; therefore, the single 7-alpha methyl intermediate can be obtained through simple treatment without chromatographic separation, the purification process is simple, and the purity of the final product reaches 99.0% or above, and the yield is higher than 60%; the raw materials are cheap and easily available, the reaction steps are few, the reaction conditions are mild and safe, and the control operation is easy; in addition, reagents used in the reaction are low in environmental pollution, and good economic and social benefits are achieved.

Biotransformation of tissue-specific hormone tibolone with fungal culture Trichothecium roseum

Whole cells based biotransformation is an important tool for bioconversion of steroids. It can be used to synthesize biologically potent compounds with diverse structures. Biotransformation of tissue-specific hormone tibolone (1) with Trichothecium roseum

Method of producing tibolone metabolites by fermentation with Rhizopus stolonifer

A new method of producing metabolites of tibolone comprising fermenting tibolone with Rhizopus stolonifer (ATCC 12938) resulting in the formation of Δ4-Tibolone (C21H28O2), 6β-Hydroxytibolone, and 15β-Hydroxytibolone (C21H28O3) is reported.

Alpha-glucosidase and tyrosinase inhibitors from fungal hydroxylation of tibolone and hydroxytibolones

Sixteen new and one known metabolites 4-20 were obtained by incubation of tibolone (1) and hydroxytibolones (2 and 3) with various fungi. Their structures were elucidated by means of a homo and heteronuclear 2D NMR and by HREI-MS techniques. The relative stereochemistry was deduced by 2D NOESY experiment. Metabolites of tibolone (1) exhibited significant inhibitory activities against α-glucosidase and tyrosinase enzymes. Hydroxylations at C-6, C-10, C-11, C-15 positions and α,β-unsaturation at C-1/C-2, C-4/C-5 showed potent inhibitory activities against these enzymes.

Anti-tumor-promoting activity of tibolone and its metabolites

The aim of this study was to evaluate the cancer chemopreventive potential of the widely prescribed drug tibolone (17α-ethynyl-7α-methyl-5(10)- estren-3-one, CAS 5630-53-5) and its main metabolites, 17α-ethynyl- 7α-methyl-4-estren-3-one (CAS 1162-60-3), 17α-ethynyl-7α- methyl-5(10)-estrene-3α,17β-diol (CAS 100239-44-9) and 17α-ethynyl-7α-methyl-5(10)-estrene-3β,17β-diol (CAS 100239-45-0), by studying their anti-tumor-promoting activity. To this aim the test compounds were submitted to the short term in vitro assay for the inhibition of Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) as a primary screening for anti-tumor promoters. All the compounds showed high inhibitory activity and low cytotoxicity as compared to literature data. To extend the study to an animal model, tibolone and its 3α-hydroxy metabolite (CAS 100239-44-9) were also assayed in the in vivo two-stage on mouse skin carcinogenesis test, exhibiting significant inhibitory effects on TPA promoted mouse skin papillomas formation. A comparison with literature data indicated them as more potent compounds than other steroids previously studied such as digitoxigenin, cortisone, hydrocortisone, and prednisolone. ECV Editio Cantor Verlag.

PROCESS AND INTERMEDIATES TO PREPARE l7?-hydroxy-7alpha-methyl-19-nor-17alpha-pregn-5(10)-en-20-yn-3-one

The present invention is a process for the preparation of l7?-hydroxy-7alpha-methyl-19-nor-17alpha-pregn-5(10)-en-20-yn-3-one (17alpha-ethynyl-l7?-hydroxy-7alpha-methyl-5(10)-estren-3-one, tibolone) of formula 1, which comprises hydrolysis of 17alpha-ethynyl-l7?-hydroxy-7alpha-methyl-5(10)-estrene 3,3-cyclic ketals of formula 2, where groups R1, R2, R3 and R4 are hydrogen atoms or alkyl groups, or R1 and R3, taken together with the carbon atoms within the dioxolane ring to which they are attached, form an alicyclic ring fused to the dioxolane ring, with R2 and R4 being hydrogen atoms, or R1 and R3 together with the carbon atoms to which they are attached form an aromatic ring fused to the dioxolane ring, where R2 and R4, taken together, form a chemical bond within said aromatic ring. In addition, the present invention includes an intermediate, compound of formula 2 and two processes to prepare 17alpha-ethynyl-17(3-hydroxy-7alpha-methyl-5(10)-estrene 3,3-cyclic ketals of formula 2: (a) by contacting 17alpha-ethynyl-l7?hydroxy-7alpha-methyl-4-estren-3-one with vicinal diols in the presence of a protic acid, and (b) by contacting 7alpha-methyl-5(10)-estrene-17-one 3,3-cyclic ketals of formula 4, where R1-R4 are defined as above, with metal acetylides, in inert solvents.