12 results about "Exemestane" patented technology

The method comprises the following steps: taking androstane-3-ketone-4-ene-17beta-carboxylic acid shown in a formula II as a raw material, carrying out decarboxylation hydroxylation, sulfonylation, elimination and double-bond oxidative cracking to prepare the exemestane intermediate shown in a formula VI, and then sequentially carrying out allylic oxidation, wittig reaction and 1, 2, 4-trimethyl-1, 3, 4-trimethyl-1, 3, 4-trimethyl-1, 3, 4-trimethyl-1, 3, 4-trimethyl-1, 3, 4-trimethyl-1, 3, 4-trimethyl-1, 3-trimethyl-1, 3, 4-trimethyl-1, 3, 4-trimethyl-1, 3-trimethyl-1, 3, 4-trimethyl-1, 3 the exemestane shown in the formula I is prepared through the step of 1, 2-site dehydrogenation. The method has the characteristics of simple process operation, mild conditions, high reaction yield and the like, and is suitable for industrial production.

The invention belongs to the field of bioengineering pharmacy, and particularly relates to a method for preparing high-standard exemestane through microbial conversion. According to the method, Nocardia simplex Noc (PN)-TS001 is adopted as a fermentation strain, methylenide is efficiently converted by microorganisms to prepare high-standard exemestane, and through optimization and combination of processes of all stages such as methylenide pretreatment, microorganism fermentation conversion and extraction refining, the substrate feeding concentration is increased to 1%-8%, the conversion rate reaches 88%-95%, the total yield reaches 88%-90%, and the yield of exemestane is increased to 90%. The detection content of the prepared exemestane refined product is more than 99.5%, the impurity content is less than 0.1%, and each index meets the USP standard. The method is simple and feasible in process, environment-friendly, low in cost, high in conversion efficiency, high in yield and high in product quality, and has a very good industrial application prospect.

The present patent application discloses a new use of exemestane, and specifically discloses the use of exemestane in treating diseases with reduced nerve function, including cerebral ischemia-reperfusion injury, cerebral infarction, Parkinson's disease, etc. In long-term research, it is found that exemestane has a neuroprotective effect, can prevent or delay the death of nerve cells, and has a therapeutic effect on diseases with reduced nerve function, such as cerebral ischemia-reperfusion injury and cerebral infarction.

The invention provides an application of exemestane or a derivative thereof in preparation of a medicine for preventing radioactive intestinal injury, and also provides a pharmaceutical composition for preventing radioactive intestinal injury, which consists of exemestane or a derivative thereof and pharmaceutically acceptable auxiliary materials. According to the invention, exemestane is screened and locked at high throughput from 3067 compound libraries approved by FDA for the first time. A radioactive intestinal injury mouse model verifies that 6.25 mg / kg exemestane is given for intragastric therapy 2 hours before the whole body is irradiated by 8 Gy, and the survival rate of the mouse can be remarkably increased. HE histology shows that the integrity of intestinal crypt-villus structures of mice in an exemestane administration group is recovered, the empty degree of marrow cavities is relieved, and spleen injury is relieved. The results prove that exemestane can protect intestinal tracts, hematopoietic organs and immune organs at the same time at the whole animal level, and the exemestane is a rare multi-organ integrated protection small molecule compound so far. The invention provides a new basis for exemestane or the derivative thereof to prevent radioactive intestinal injury.

Biotransformation of gestonorone acetate (1) with Cunninghamella blakesleeana (ATCC 8688) yielded a new analogue, 17α-actoxy-10β,11β-dihydroxy-progesterone (2). Compound 2 was identified as non-cytotoxic inhibitor of human aromatase enzyme (IC50=0.827±0.066 μM). Compound 2 showed a significant aromatase inhibitory activity, as compared to the standard aromatase inhibitory drug, exemestane (IC50=0.232±0.03 μM).

The application provides an application of exemestane or a derivative thereof in preparation of a medicine for protecting against radiation-induced intestinal injury, and further provides a medicine composition for protecting against radiation-induced intestinal injury, which is composed of exemestane or a derivative thereof and pharmaceutically acceptable adjuvants. The application first screens and locks the exemestane from a high-throughput screening of 3067 compounds approved by FDA. Through a mouse model of radiation-induced intestinal injury, it is verified that the survival rate of mice can be significantly improved by intragastrically treating the mice with 6.25 mg / kg of exemestane 2 hours before whole body 8 Gy irradiation. HE histology shows that the intestinal crypt-villus structure integrity of the mice in the exemestane administration group is recovered, the bone marrow cavity emptiness degree is reduced, and the spleen injury is reduced. The above results prove that the exemestane can protect the intestine, hematopoietic and immune organs at the whole animal level, and is a rare small molecule compound for protecting multiple organs. The application provides a new basis for exemestane or a derivative thereof for protecting against radiation-induced intestinal injury.

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 provides an improved method for preparing an exemestane intermediate 6-hydroxymethyl-androstane-1, 4-diene-3, 17-diketone, and particularly relates to a method for preparing the 6-hydroxymethyl-androstane-1, 4-diene-3, 17-diketone through a reaction of 1, 3-ditetrahydropyrrolyl-androstane-3, 5-diene-17-ketone under the action of phenol and a formaldehyde aqueous solution, and particularly relates to a method for preparing the 6-hydroxymethyl-androstane-1, 4-diene-3, 17-diketone through the reaction of 1, 3-ditetrahydropyrrolyl-androstane-3, 5-diene-17-ketone. Compared with the prior art, the method has the advantages that the generation of a large amount of bis-hydroxymethylation impurities is avoided, the purity and the yield are improved, the cost is reduced, the stability of the process is improved, and industrialization is facilitated.

The invention provides a preparation method of exemestane, and belongs to the technical field of raw material medicine preparation, and the preparation method comprises the following steps: step S1, androstenedione is adopted as a raw material, under the catalysis of cuprous oxide, an iodination reaction is carried out, and 2-iodo-4-ene-3, 17-androstenedione is obtained; step S2, enabling the 2-iodo-4-ene-3, 17-androstanedione to react with diethanol formal under the action of phosphorus oxychloride, so as to generate 2-iodo-6-methylene-4-ene-3, 17-androstanedione, and enabling the 2-iodo-6-methylene-4-ene-3, 17-androstanedione to react with the diethanol formal under the action of phosphorus oxychloride; and S3, carrying out an oxidation reaction on the 2-iodo-6-methylene-4-ene-3, 17-androstanedione to obtain a crude product, and refining the crude product to obtain the exemestane. According to the preparation route, cheap peroxydisulfate is used for replacing expensive oxidizing reagents such as DDQ, the cost is reduced, and the economic benefit is further improved due to the high yield of the oxidation step.

The invention discloses a preparation method of exemestane EP pharmacopoeia C impurity. According to the preparation method, a low-cost intermediate is used as a starting material, a common formaldehyde aqueous solution, p-toluenesulfonic acid and enzyme catalytic reaction are used, high-toxicity and high-harm reagents are reduced, and side reactions are reduced; 6-bit and 16-bit methylene structure construction is completed in one step by heating and pressurizing, the post-treatment workload is reduced, the subsequent purification difficulty is reduced, the yield is improved, and the method has remarkable significance in quality control of exemestane.

The invention discloses application of exemestane in preparation of a medicine for treating spontaneous cerebral hemorrhage. The invention proposes and verifies that exemestane can effectively reduce the hematoma area after spontaneous cerebral hemorrhage, maintain the brain tissue structure, relieve immune cell infiltration, avoid brain cell apoptosis, promote motor function recovery and improve anxiety behaviors for the first time, and provides a new direction for treatment of spontaneous cerebral hemorrhage.

The invention relates to the technical field of drug detection, and discloses a method for detecting beta-lactam compound residues in a drug, which comprises the following steps of: extracting and diluting beta-lactam compounds in the drug through a uniform pretreatment process (adopting 50% acetonitrile) in combination with optimized LC-MS / MS conditions (including specific chromatographic columns, gradient elution procedures and mass spectrum parameters); synchronous quantitative detection of eight beta-lactam compounds (covering cephalosporin and penem) in five raw material medicines (exemestane, etoposide, abiraterone acetate, emtricitinib and cilnimod) with remarkable structural difference is realized, and the limit of quantitation is as low as 0.008 ppm. According to the method, the detection sensitivity is remarkably improved, the trace residue monitoring requirement is met, pretreatment steps are simple and universal, conditions do not need to be adjusted according to different raw material medicines, the detection efficiency and the method applicability are greatly improved, and the problems that the sensitivity is insufficient and the universality is poor in the prior art are effectively solved.