37 results about "Toremifene" patented technology

This invention relates to the treatment of androgen receptor-positive breast cancer in a subject, for example a female subject. Accordingly, this invention provides methods of: a) treating a subject suffering from breast cancer; b) treating a subject suffering from metastatic breast cancer; c) treating a subject suffering from refractory breast cancer; d) treating a subject suffering from AR-positive breast cancer; e) treating a subject suffering from AR-positive refractory breast cancer; f) treating a subject suffering from AR-positive metastatic breast cancer; g) treating a subject suffering from AR-positive and ER-positive breast cancer; h) treating a subject suffering from triple negative breast cancer; i) treating a subject suffering from advanced breast cancer; j) treating a subject suffering from breast cancer that has failed SERM (tamoxifen, toremifene), aromatase inhibitor, trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, exemestane (Aromasin), bevacizumab (Avastin), and / or fulvestrant treatments; k) treating, preventing, suppressing or inhibiting metastasis in a subject suffering from breast cancer; l) prolonging survival of a subject with breast cancer, and / or m) prolonging the progression-free survival of a subject with breast cancer; comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound, comprising administering to the subject a therapeutically effective amount of a SARM compound of this invention.

This invention provides a method of treating androgen-deprivation induced osteoporosis, bone fractures or loss of bone mineral density (BMD) in a male human subject suffering from prostate cancer by administering a pharmaceutical composition comprising Toremifene and / or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof, to the subject.

Novel methods for treating or reducing the likelihood of acquiring vaginal dysfunctions, more particularly vaginal dryness and dyspareunia, leading to sexual dysfunction and low sexual desire and performance, in susceptible warm-blooded animals including humans involving administration of a sex steroid precursor. Further administration of estrogen or selective estrogen receptor modulator, particularly those selected from the group consisting of Raloxifene, Arzoxifene, Tamoxifen, Droloxifene, Toremifene, Iodoxifene, GW 5638, TSE-424, ERA-923, and lasofoxifene, and more particularly compounds having the general structure:is specifically disclosed for the medical treatment and / or inhibition of development of some of these above-mentioned diseases. Pharmaceutical compositions for delivery of active ingredient(s) and kit(s) useful to the invention are also disclosed.

The invention provides a synthetic method of toremifene. The synthesis method comprises: step S1, making a MacMurray reaction between compound B having structural formula II and compound C having structural formula III to obtain compound D having structural formula IV; step S2, making compound D react with compound E having structural formula V or The hydrochloride of compound E undergoes a selective alkylation reaction on the phenolic hydroxyl group to obtain compound F with structural formula VI; step S3, reacting compound F with thionyl chloride to obtain toremifene, wherein structural formula II is : Structural formula III is: Structural formula IV is Structural formula Ⅴ is ClCH 2 CH 2 N(CH 3 ) 2 ; Structural formula Ⅵ is The stereoselectivity of the obtained compound D is higher, so when using it as an intermediate to synthesize toremifene, the reaction yield of the toremifene of the Z configuration can be increased, and the toremifene of the Z configuration can be improved. purity; and the process is stable, the reaction conditions are mild, the intermediates are easy to separate, and can be used for large-scale production.

This invention relates to the treatment of breast cancer in a subject, for example a female subject. Including methods of: treating metastatic breast cancer; refractory breast cancer; AR-positive breast cancer; AR-positive refractory breast cancer; AR-positive metastatic breast cancer; AR-positive and ER-positive breast cancer; triple negative breast cancer; advanced breast cancer; breast cancer that has failed SERM (tamoxifen, toremifene), aromatase inhibitor, palbociclib (Ibrance), trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, exemestane (Aromasin), bevacizumab (Avastin), and / or fulvestrant treatments; metastasis in a subject suffering from breast cancer; and / or HER2-positive; comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound.

This invention relates to the treatment of breast cancer in a subject, for example a female subject. Including methods of: treating metastatic breast cancer; refractory breast cancer; AR-positive breast cancer; AR-positive refractory breast cancer; AR-positive metastatic breast cancer; AR-positive and ER-positive breast cancer; triple negative breast cancer; advanced breast cancer; breast cancer that has failed SERM (tamoxifen, toremifene), aromatase inhibitor, trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, exemestane (Aromasin), bevacizumab (Avastin), and / or fulvestrant treatments; metastasis in a subject suffering from breast cancer; comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound.

The invention relates to a preparation method of citric acid toremifene intermediates 4-[2-(N,N-dimethylamino)ethyoxyl diphenylketone and 1,2-diphenyl-1-[4[2-[2-N,N- dimethylamino]ethoxyl]-1,4-butanediol. The preparation method of the 4-[2-(N,N-dimethylamino)ethyoxyl diphenylketone comprises the steps that 4-hydroxy diphenyl ketone, inorganic alkali, a first solvent and a second solvent are mixed and are stirred at the temperature of 53-58 DEG C for 0.8-2 hours, then cooling is performed to 40 DEG C or below, N,N-dimethylamino chloroethane hydrochloride is added, heating is performed to reach 80-85 DEG C, and stirring reaction is performed for 2-5 hours; cooling is performed to 40 DEG C or below, drinking water is added, stirring is performed to make the mixture layered, and an upper-layer oil phase is taken; the oil phase is washed with 4% sodium hydroxide solution till it is detected through TLC that the 4-hydroxy diphenyl ketone disappears, then washing is performed with drinking water till pH is 8-9; the obtained product is subjected to decompression at the temperature of 55-60 DEG C to evaporate out the solvent, and the citric acid toremifene intermediates 4-[2-(N,N-dimethylamino)ethyoxyl diphenylketone is obtained after cooling.

This invention relates to the treatment of androgen receptor-positive breast cancer in a subject, for example a female subject. Accordingly, this invention provides methods of: a) treating a subject suffering from breast cancer; b) treating a subject suffering from metastatic breast cancer; c) treating a subject suffering from refractory breast cancer; d) treating a subject suffering from AR-positive breast cancer; e) treating a subject suffering from AR-positive refractory breast cancer; f) treating a subject suffering from AR-positive metastatic breast cancer; g) treating a subject suffering from AR-positive and ER-positive breast cancer; h) treating a subject suffering from triple negative breast cancer; i) treating a subject suffering from advanced breast cancer; j) treating a subject suffering from breast cancer that has failed SERM (tamoxifen, toremifene), aromatase inhibitor, trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, exemestane (Aromasin), bevacizumab (Avastin), and / or fulvestrant treatments; k) treating, preventing, suppressing or inhibiting metastasis in a subject suffering from breast cancer; l) prolonging survival of a subject with breast cancer, and / or m) prolonging the progression-free survival of a subject with breast cancer; comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound, comprising administering to the subject a therapeutically effective amount of a SARM compound of this invention.

Novel methods for treating or reducing the likelihood of acquiring vaginal dysfunctions, more particularly vaginal dryness and dyspareunia, leading to sexual dysfunction and low sexual desire and performance , in susceptible warm-blooded animals including humans involving administration of a sex steroid precursor. Further administration of estrogen or selective estrogen receptor modulator, particularly those selected from the group consisting of Raloxifene, Arzoxifene, Tamoxifen, Droloxifene, Toremifene, Iodoxifene, GW 5638, TSE-424, ERA-923, and lasofoxifene, and more particularly compounds having the general structure:is specifically disclosed for the medical treatment and / or inhibition of development of some of these above-mentioned diseases. Pharmaceutical compositions for delivery of active ingredient(s) and kit(s) useful to the invention are also disclosed.

This invention relates to the treatment of breast cancer in a subject, for example a female subject. Including methods of: treating metastatic breast cancer; refractory breast cancer; AR-positive breast cancer; AR-positive refractory breast cancer; AR-positive metastatic breast cancer; AR-positive and ER-positive breast cancer; triple negative breast cancer advanced breast cancer; breast cancer that has failed SERM (tamoxifen, toremifene), aromatase inhibitor, trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, exemestane (Aromasin), bevacizumab (Avastin), and / or fulvestrant treatments; metastasis in a subject suffering from breast cancer; comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound.

This invention relates to the treatment of breast cancer in a subject, for example a female subject. The breast cancer includes metastatic breast cancer, refractory breast cancer, AR-positive breast cancer, AR-positive refractory breast cancer, AR-positive metastatic breast cancer, AR-positive and ER-positive breast cancer, triple negative breast cancer, advanced breast cancer, breast cancer that has failed SERM (tamoxifen, toremifene), aromatase inhibitor, trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, exemestane (Aromasin), bevacizumab (Avastin), and / or fulvestrant treatments, and metastasis in a subject suffering from breast cancer. The method comprises administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound.

This invention relates to the treatment of breast cancer in a subject, for example a female subject. Including methods of: treating metastatic breast cancer; refractory breast cancer; AR-positive breast cancer; AR-positive refractory breast cancer; AR-positive metastatic breast cancer; AR-positive and ER-positive breast cancer; triple negative breast cancer; advanced breast cancer; breast cancer that has failed SERM (tamoxifen, toremifene), aromatase inhibitor, palbociclib (Ibrance), trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, exemestane (Aromasin), bevacizumab (Avastin), and / or fulvestrant treatments; metastasis in a subject suffering from breast cancer; and / or HER2-positive; comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound.

This invention relates to the treatment of breast cancer in a subject, for example a female subject. Including methods of: treating metastatic breast cancer; refractory breast cancer; AR-positive breast cancer; AR-positive refractory breast cancer; AR-positive metastatic breast cancer; AR-positive and ER-positive breast cancer; triple negative breast cancer; advanced breast cancer; breast cancer that has failed selective estrogen receptor modulator (SERM) (tamoxifen, toremifene, raloxifene), gonadotropin-releasing hormone (GnRH) agonist (goserelin), aromatase inhibitor (AI) (letrozole, anastrozole, exemestane), cyclin-dependent kinase 4 / 6 (CDK 4 / 6) inhibitor (palbociclib (Ibrance), ribociclib (Kisqali), abemaciclib (Vorzenio)), mTOR inhibitor (everolimus), trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, neratinib (Nerlynx), olaparib (Lynparza) (an inhibitor of the enzyme poly ADP ribose polymerase (PARP)), bevacizumab (Avastin), and / or fulvestrant treatments; metastasis in a subject suffering from breast cancer; HER2-positive; treating a subject suffering from ER mutant expressing breast cancer and / or treating breast cancer in a subject, by first determining the 18F-16β-fluoro-5α-dihydrotestosterone (18F-DHT) tumor uptake and identifying said subject as having AR-positive breast cancer based on 18F-DHT tumor uptake, comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound.

A method of treatment of erectile dysfunction (ED) comprises the step of administering fispemifene to a subject in need thereof in an amount effective to raise the subject's testosterone level. Fispemifene may be used in combination with a PDE-5 inhibitor in individuals who have failed to respond sufficiently to conventional ED treatment. Methods are also disclosed of treating ED by administering clomifene, enclomifene, ospemifene, toremifene and mixtures thereof in combination with a PDE-5 inhibitor.

A method of treatment of erectile dysfunction (ED) comprises the step of administering fispemifene to a subject in need thereof in an amount effective to raise the subject's testosterone level. Fispemifene may be used in combination with a PDE-5 inhibitor in individuals who have failed to respond sufficiently to conventional ED treatment. Methods are also disclosed of treating ED by administering clomifene, enclomifene, ospemifene, toremifene and mixtures thereof in combination with a PDE-5 inhibitor.

This invention provides a method of treating androgen-deprivation induced osteoporosis, bone fractures or loss of bone mineral density (BMD) in a male human subject suffering from prostate cancer, wherein the subject has a precipitous decline in androgen levels, by administering a pharmaceutical composition comprising Toremifene or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof, to the subject, wherein the method increases bone density without increasing androgen and specifically testosterone levels in the subject.

The present invention provides methods for reducing the incidence of, inhibiting, suppressing, and treating androgen-deprivation induced osteoporosis, bone fractures and / or loss of bone mineral density (BMD) in men having prostate cancer, comprising administering to a male human subject having prostate cancer a toremifene and / or its analog, derivative, isomer, metabolite. pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide. or any combination thereof. The present invention also provides methods of treating, preventing, suppressing, inhibiting, or reducing the incidence of hot flashes, gynecomastia, and / or hair loss in a subject, comprising same.

A method for treating or preventing cardiovascular pathologies by administering a compound of the formula (I): wherein Z is C═O or a covalent bond; Y is H or O(C1-C4)alkyl, R1 and R2 are individually (C1-C4)alkyl or together with N are a saturated heterocyclic group, R3 is ethyl or chloroethyl, R4 is H, R5 is I, O(C1-C4)alkyl or H and R6 is I, O(C1-C4)alkyl or H with the proviso that when R4, R5, and R6 are H, R3 is not ethyl; or a pharmaceutically acceptable salt thereof, effective to elevate the level of TGF-beta to treat and / or prevent conditions such as atherosclerosis, thrombosis, myocardial infarction, and stroke is provided. Useful compounds include idoxifene, toremifene or salts thereof. Further provided is a method for identifying an agent that elevates the level of TGF-beta. Another embodiment of the invention is an assay or kit to determine TGF-beta in vitro. Also provided is a therapeutic method comprising inhibiting smooth muscle cell proliferation associated with procedural vascular trauma employing the administration of tamoxifin or structural analogs thereof, including compounds of formula (I).

The invention relates to a preparation method of tamoxifen. The preparation method is characterized by comprising the following steps of adding toremifene, a catalyst and an alkali compound into an alcohols solvent, and stirring for reacting for 10 to 24 hours at a hydrogen atmosphere at 0.1 to 1.0MPa and 20 to 150 DEG C; then cooling a reaction system to the room temperature, carrying out suction filtration, and vaporizing and eliminating the solvent at normal pressure or reduced pressure; adding ethyl acetate and water for washing, standing for layering, drying an upper-layer organic phase with anhydrous sodium sulfate, filtering to remove sodium sulfate, vaporizing and eliminating the ethyl acetate at reduced pressure, obtaining a pulp, and adding acetone into the pulp, wherein the ratio of the volume of the acetone to the weight of the pulp is 2 to 5ml / g; then heating to 50 to 56 DEG C for dissolving, and cooling to 0 DEG C for separating crystals out; drying the crystals to obtain the white needle-like solid tamoxifen.

This invention relates to the treatment of breast cancer in a subject, for example a female subject. Including methods of: treating metastatic breast cancer; refractory breast cancer; AR-positive breast cancer; AR-positive refractory breast cancer; AR-positive metastatic breast cancer; AR-positive and ER-positive breast cancer; triple negative breast cancer; advanced breast cancer; breast cancer that has failed selective estrogen receptor modulator (SERM) (tamoxifen, toremifene, raloxifene), gonadotropin-releasing hormone (GnRH) agonist (goserelin), aromatase inhibitor (AI) (letrozole, anastrozole, exemestane), cyclin-dependent kinase 4 / 6 (CDK 4 / 6) inhibitor (palbociclib (Ibrance), ribociclib (Kisqali), abemaciclib (Vorzenio)), mTOR inhibitor (everolimus), trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, neratinib (Nerlynx), olaparib (Lynparza) (an inhibitor of the enzyme poly ADP ribose polymerase (PARP)), bevacizumab (Avastin), and / or fulvestrant treatments; metastasis in a subject suffering from breast cancer; HER2-positive; and / or treating a subject suffering from ER mutant expressing breast cancer, comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound.