9 results about "Raloxifene" patented technology

This invention discloses a method for preparing raloxifene EP impurity B, comprising the following steps: dissolving 6-methoxy-2-(4-methoxyphenyl)benzothiophene (Ⅰ) as a raw material in solvent one, adding NIS, and then adding a free radical initiator to react and obtain intermediate III; dissolving 4-[2-(1-pyrrolidinyl)ethoxy]benzoate salt (II) in solvent two, adding solvent two or not, and then adding a chlorinating agent to react and generate intermediate IV; dissolving intermediate III in solvent three, adding a Lewis acid, and then adding intermediate IV, and performing a Friedel-Crafts acylation reaction to generate intermediate V; dissolving intermediate V in solvent four, adding a demethylating agent, and generating bisphenol hydroxyl intermediate VI under demethylation conditions; dissolving intermediate VI in solvent five, adding a reducing agent, and generating intermediate VII through a reduction reaction; dissolving intermediate VII in formic acid, stirring, evaporating, and finally lyophilizing to generate the formate target product VIII.

The present invention relates to the technical field of molecular imaging probes, and more specifically to a fluorescent probe targeting the estrogen receptor, a preparation method, and applications thereof. The fluorescent probe targeting the estrogen receptor is composed of a fluorescein ester, an estrogen receptor recognition group, raloxifene, and an alkane chain. The preparation method comprises the following steps: Step S1, hydrolyzing or hydrogenolyzing the carbamate of raw material I to synthesize an amino intermediate II; Step S2, condensing the amino intermediate II with FITC to obtain a fluorescent probe targeting the estrogen receptor III. The fluorescent probe targeting the estrogen receptor in the present invention can avoid the effects of short emission wavelength and low signal-to-noise ratio during probe application, and can be better used to promote the clinical application of the fluorescent probe targeting the estrogen receptor.

The invention provides an application of raloxifene or a pharmaceutical salt thereof in a medicine for treating CryAB mutant cardiomyopathy. According to the invention, based on a CryAB R120G mutation model, core pathological characteristics of CryAB mutation cardiomyopathy, including formation of protein aggregates in myocardial cells and heart failure performance, are simulated. The raloxifene is used for relieving cardiac hypertrophy, inhibiting myocardial fibrosis and removing CryAB protein aggregate, and has the effect of inducing myocardial remodeling by CryAB mutation. The pharmacological action of the raloxifene is verified through multi-level experiments from in-vitro cells to in-vivo mice, and research results show that the raloxifene and the pharmaceutical salt thereof have potential application value in treatment of the conjunctin-related cardiomyopathy, and a new strategy and an experimental verification path are provided for research of the hereditary cardiomyopathy.

The invention belongs to the technical field of medicinal chemistry, and relates to a novel crystal form of lafamorin and a preparation method thereof, in particular to a medicinal crystal form X and a medicinal crystal form Y of lafamorin and a preparation method of the medicinal crystal form X and the medicinal crystal form Y.

The invention discloses a preparation method of a rafenasin intermediate, which comprises the following steps of: adding initial materials SM-1 and SM-2 and alkali according to a specific reaction feeding sequence and reaction temperature, heating to the specific reaction temperature (90-110 DEG C), and dropwise adding diphenyl azide phosphate, so that compared with the prior art (contrast 1, 2), the preparation method has the advantages that the urea impurity 1, 3-bis (1, 2, 3-triazole-1-yl)-1, 3-diketone in the reaction is effectively controlled, and the yield of the rafenasin intermediate is improved. The method can be used for producing (1, 1 '-biphenyl)-2-ylurea (less than 5%), the reaction conversion rate is increased, and the whole synthetic route has the advantages of milder and safer reaction conditions, lower production cost and lower environmental pollution.

This invention relates to the treatment of breast cancer in a subject, and the subject can be either a male or 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), lerociclib, abemaciclib (Vorzenio), trilaciclib, lerociclib), mTOR inhibitor (everolimus), trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), alpelisib (Piqray) (an inhibitor of phosphatidylinositol-3-kinase subunit alpha (PI3Kα)), 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 and a cyclin-dependent kinase 4 / 6 (CDK 4 / 6) inhibitor.

The invention discloses a preparation method of a raloxifene EP impurity B. The preparation method comprises the following steps: taking 6-methoxy-2-(4-methoxyphenyl) benzothiophene (I) as a raw material, dissolving the 6-methoxy-2-(4-methoxyphenyl) benzothiophene (I) in a solvent I, adding NIS, then adding a free radical initiator, and reacting to obtain an intermediate III; dissolving 4-[2-(1-pyrrolidinyl) ethyoxyl] benzoic acid hydrochloride (II) in a solvent II, adding the solvent II or not, then adding a chlorinating agent, and reacting to generate an intermediate IV; dissolving the intermediate III in a solvent III, adding Lewis acid, then adding the intermediate IV, and carrying out Friedel-Crafts acylation reaction to generate an intermediate V; dissolving the intermediate V in a solvent IV, adding a demethylation reagent, and generating a bisphenol hydroxyl intermediate VI under a demethylation condition; dissolving the intermediate VI in a solvent V, adding a reducing agent, and performing reduction reaction to generate an intermediate VII; and dissolving the intermediate VII in formic acid, stirring, spin-drying, and finally freeze-drying to generate a formate target product VIII.

The application discloses application of raloxifene or a pharmaceutical salt thereof in preparation of a medicine for treating sepsis cardiomyopathy, and simultaneously discloses application of a STAT3 protein Tyr705 site as a sepsis cardiomyopathy treatment target, and belongs to the technical field of biological medicines. The application proves through in-vivo and in-vitro experiments that raloxifene can effectively improve body temperature drop and left ventricular systolic function reduction related to sepsis cardiomyopathy, reduce myocardial inflammatory infiltration, relieve myocardial oxidative stress, mitochondrial dysfunction and energy metabolism disorder, and play a definite myocardial protection role by inhibiting phosphorylation activation of the STAT3 protein Tyr705 site in myocardial tissue and cells. The application provides a novel targeted treatment strategy and drug selection for sepsis cardiomyopathy, and has a good clinical transformation application prospect.

The invention relates to a method of producing a hydrate of Raloxifene (RLX) with increased solubility and to a hydrate of RLX produced according to the method. Also provided are pharmaceutical compositions comprising a hydrate of RLX prepared according to the method. The invention further relates to a hydrate of RLX or pharmaceutical compositions comprising the hydrate of RLX for use in methods of preventing and / or treating osteoporosis and / or cancer. In particular, the hydrate of RLX is prepared by combining a co-former mixture of RLX, or a salt thereof, and Arginine.