28results about "Estrane derivatives" patented technology

Provided herein are 19-nor C3,3-disubstituted C21-pyrazolyl steroids of Formula (I):and pharmaceutically acceptable salts thereof; wherein , R1, R2, R3a, R3b, R4a, R4b, R5, R6, and R7 are as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and / or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and / or withdrawal syndromes, and tinnitus.

The present invention relates to a process for preparing (15α,16α,17β)-Estra-1,3,5(10)-triene-3,15,16,17-tetrol, also known as Estetrol, having the formula shown below:

The present invention relates to a process for the preparation of a compound of formula (I), a stereoisomer, a salt, a hydrate or a solvate thereof, comprising the step of desulfinylation of a compound of formula (II) to produce compound of formula (I); wherein: R1 and R2 are as defined in the claims, wherein said desulfinylation step is performed by continuous flow process.

The present application relates to an intermediate of fulvestrant and a preparation method thereof. Specifically, the present application relates to a compound as shown in formula V and a preparation method thereof, wherein R 1 is hydrogen or a hydroxyl protecting group. The present application also relates to a preparation method for synthesizing fulvestrant via the compound as shown in formula V, which has the advantages of short reaction steps, mild and safe reaction conditions, high selectivity, simple operation and purification, high synthesis efficiency, and is suitable for large-scale production.

This invention discloses a method for synthesizing estradiol benzoate. The method uses toluene as a solvent and benzoic anhydride as an acylation reagent. While ensuring synthesis efficiency and quality, it effectively avoids the safety risks and high costs associated with the use of reagents in existing technologies. No special storage and operating conditions are required during the production process, and the product quality is controllable, making it suitable for industrial production.

The present invention proposes a process for preparing high-purity estetrol, which uses (17β)-3-(phenylmethoxy)-estra-1,3,5(10),15-tetraen-17-ol acetate as a raw material, introduces hydroxyl groups at positions 15 and 16 through a dihydroxylation reaction, protects the hydroxyl groups at positions 15 and 16 through a ketal reaction, separates isomers, and then sequentially removes the benzyl protecting group, the acyl group, and the ketal protecting group. Finally, the process is purified to obtain a compound of formula (I) #imgabs0#. The present invention uses a ketal method to protect the hydroxyl groups at positions 15 and 16, and then separates the isomers, thereby achieving a satisfactory isomer removal effect and refining yield. Moreover, the process is convenient, and the ketal reaction only requires the use of an organic ketone reagent and a catalytic amount of acid. The organic ketone reagent can be completely recovered and reused, and almost no waste is generated.

The invention belongs to the technical field of immunodetection, and discloses an E2 sandwich-method rabbit monoclonal antibody mAb9 or an antigen binding fragment thereof as well as a preparation method and application of the E2 sandwich-method rabbit monoclonal antibody mAb9 or the antigen binding fragment thereof. The E2 sandwich method rabbit monoclonal antibody mAb9 or an antigen binding fragment thereof comprises a light chain variable region VL and a heavy chain variable region VH, the light chain variable region VL comprises complementary determining regions LCDR1, LCDR2 and LCDR3, and the heavy chain variable region VH comprises complementary determining regions HCDR1, HCDR2 and HCDR3. The monoclonal antibody can be combined with an E2 compound in a high-specificity mode, is suitable for double-antibody sandwich immunodetection and is applied to an immunodetection kit prepared through double-antibody sandwich ELISA or a chemiluminescence method, a double-antibody sandwich chemiluminescence platform is used for detecting an E2 standard antigen, the detection sensitivity is lower than 10 pg / mL, a clinical sample is detected through a magnetochemiluminescence method, and the detection sensitivity is lower than 10 pg / mL. Within the sample range of 0-15000 pmol / L, the correlation with clinical comparison is good, and clinical management is provided for female health and male health.

Provided herein are 19-nor C3,3-disubstituted C21-pyrazolyl steroids of Formula (I): and pharmaceutically acceptable salts thereof, wherein - - - - -, R1, R2, R3a, R3b, R4a , R4b, R5, R6, and R7 are as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and / or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and / or withdrawal syndromes, and tinnitus.

The present invention relates to a process for the preparation of (15 [alpha], 16 [alpha], 17 [beta])-estra-1, 3, 5 (10)-triene-3, 15, 16, 17-tetrol monohydrate, also known as estetrol monohydrate, having the following formula (I).

The present disclosure relates to a crystallization process of (15α, 16α, 17β)-estra-1, 3,5(10)- triene-3,15,16,17-tetrol monohydrate (Estetrol monohydrate, Compound 1) Form 12. Compound 1

The present invention relates to the field of processes for preparing active pharmaceutical ingredients and, in particular, to an industrial-scale purification process of (17β)-2-methoxy-estra-1,3,5(10)-triene-3,17-diol, also known as 2-methoxyestradiol, from (17β)-4-methoxy-estra-1,3,5(10)-triene-3,17-diol, also known as 4-methoxyestradiol. The invention further relates to intermediates of this process.

The present invention relates to a process for the preparation of a compound of formula (II), a stereoisomer, salt, hydrate or solvate thereof, comprising the step of sulfinylating a compound of formula (IV) to produce a compound of formula (II); wherein: R1 and R2 are as defined in the claims; wherein the sulfinylation step is carried out in the presence of a solvent selected from the group consisting of benzene, toluene, ethylbenzene, xylene, chlorobenzene, bromobenzene, fluorobenzene, anisole, nitrobenzene, tetrahydronaphthalene, dichlorobenzene, trimethylbenzene, ethyl acetate, propyl acetate, butyl acetate, propanol, butanol, 2-methyltetrahydrofuran, diethyl ether, methyl tert-butyl ether, cyclopentylmethyl ether, dichloromethane, and tetrachloromethane, pentane, hexane, heptane, cyclohexane, decahydronaphthalene and mixtures thereof.

The invention provides an estetrol intermediate compound B as shown in a formula (I), a preparation method of the compound B and a method for preparing a compound A and estetrol from the compound B. According to the present invention, estrone is adopted as the starting material, the compound B is constructed through the olefin etherification reaction, the compound A is obtained through the oxidation reaction, and the target product compound A can be obtained through the two-step reaction, such that the synthesis route is shortened, the synthesis steps are simplified, the total yield of the reaction can achieve 82%, and the purity of the obtained compound A is more than 98%. According to the route, the reaction yield and efficiency are improved, and the obtained compound is high in purity, low in cost, beneficial to large-scale industrial production and wide in commercial application prospect. (I).

The present invention relates to novel 2-Methoxyestradiol derivatives and their medical use. In particular, the novel derivatives of the present invention are useful for the treatment or prevention of liver or lung fibrosis. Accordingly, the present invention also provides medical uses of the 2-Methoxyestradiol derivatives of the present invention. The present invention also provides a method of treating or preventing liver or lung fibrosis comprising administering an effective amount of the 2-Methoxyestradiol derivatives of the present invention.

The application discloses a synthesis method of deuterium-substituted olefin by using D2O as a deuterium source and a palladium membrane for catalysis, and belongs to the technical field of synthesis of deuterium-substituted olefin blocks. The application uses a three-chamber electrolytic cell separated by a palladium membrane and an ion exchange membrane as a reactor, uses the palladium membrane as a working electrode, uses a deuterium water solution as an electrolyte, electrolyzes the deuterium water by using a constant potential electrolysis method, transmits active deuterium formed to an organic reaction side using anhydrous ethanol or cyclohexane as an organic solvent, and then synthesizes deuterium-substituted olefin compounds by using a palladium membrane modified by sodium benzene thiol for catalyzing reduction and deuterization of acetylene compounds with high selectivity, so as to further synthesize corresponding deuterium-substituted drugs. The application provides a green, efficient, high-universality and low-cost amplification synthesis method for synthesizing deuterium-substituted olefin blocks containing easily-reduced and easily-hydrolyzed functional groups, and has a wide application prospect.

The present application belongs to the field of organic chemistry, and particularly relates to a recovery method of deoxyprogesterone recrystallization mother liquor, aiming at the problem that after the content ratio of delta 3 isomer and deoxyprogesterone in the crystallization mother liquor reaches 40:60, the deoxyprogesterone cannot be further recovered by the ordinary recrystallization method, and the following scheme is proposed, that is, the recrystallization mother liquor is subjected to side chain degradation, reduction, esterification, bromination, elimination, hydrolysis and Birch reduction to obtain a single-component deoxyprogesterone intermediate. The recrystallization mother liquor of deoxyprogesterone is high-yield converted into single-component 18-methyl-11-methylene estradiol-4-ene-17beta-ol, and the main raw material used is the original waste mother liquor in the production of deoxyprogesterone, which not only meets the high atomic utilization rate of the environmental protection production requirement, but also improves the economic benefit.

The present invention relates to a process for preparing (15α,16α,17β)-estra-1,3,5(10)-triene-3,15,16,17-tetrol monohydrate, also known as estetrol monohydrate, having formula (I). [Formula 1] JPEG2026503158000010.jpg2674

The invention discloses a small molecule compound with an estrane mother nucleus and application of the small molecule compound in preparation of a PD-L1 degradation agent or an anti-tumor drug. The small molecule compound has a structure as shown in a formula (I), firstly, in-vitro experiments find that the compound can promote PD-L1 to be degraded through a lysosome pathway and enhance the killing effect of T cells on tumor cells, so that an excellent anti-tumor effect is achieved; the in-vivo anti-tumor effect of the small molecule compound is further evaluated through animal experiments, and the result shows that the compound plays an anti-tumor role by depending on T cells, can remarkably inhibit tumor growth and reduce tumor volume, is small in toxic and side effect and high in safety, can be applied to preparation of anti-tumor drugs, and has a good market prospect.

The invention discloses a synthesis method of estradiol semihydrate. The synthesis method is particularly suitable for a process of synthesizing the estradiol semihydrate by taking ADD (1.4-androstenedione) as an initial raw material. The method comprises the following steps: firstly, carrying out ketal reaction on ADD and ethylene glycol to generate ketal, reacting the ketal with a lithiation reagent prepared from biphenyl, diphenylmethane, lithium and tetrahydrofuran to generate 17-ketal estrone, then hydrolyzing the 17-ketal estrone through inorganic acid to obtain estrone, reducing the estrone through a reducing agent to obtain an estradiol crude product, and purifying the estradiol crude product. And refining the estradiol crude product with an alcohol or ketone solvent and pure water, and drying to obtain the estradiol semihydrate. By using the method, impurities such as biphenyl, diphenylmethane and the like in lithiation reaction are removed in advance, the refining operation of the estrone is reduced (the refining of the estrone requires 30 times of volume of a solvent), the productivity is improved, the refining and drying processes of the estradiol semihydrate ensure that the content of crystal water is qualified, the single impurity of the synthesized product is less than 0.1%, and the yield is improved. The product meets the quality standards of the Chinese pharmacopoeia 2020 edition and the European pharmacopoeia 11 edition.

The object of the present invention is an improved process for the preparation of Trenbolone Acetate of formula (I) by means of crystallization, having irregular hexagonal plate-like crystal habit and / or being comprised in a particle size distribution median value (D50) ranging from 50 pm to 80 pm, or from 60 pm to 90 pm, or from 90 pm to 250 pm, wherein seed crystals having a particle size distribution median value (D50) comprised in the range from 8 pm to 15 pm, or from 15 pm to 20 pm, or from 20 pm to 90 pm, respectively, are added to a solution of Trenbolone Acetate in a solvent, wherein the solvent is a C2-C5 alkyl alcohol or a mixture thereof.

Object of the present invention is related to a process for the preparation of Trenbolone Acetate of formula (I): having a median value (D50) of the particle size distribution comprised in the range from 50 µm to 80 µm, or from 60 µm to 90 µm, or from 90 µm to 250 µm, by means of addition of a seed having a median value (D50) of the particle size distribution comprised respectively in the range from 8 µm to 15 µm, or from 15 µm to 20 µm, or from 20 µm to 90 µm, to a solution of Trenbolone Acetate in a solvent.

The present invention refers to the sector of the processes for the preparation of active ingredients for pharmaceutical use, and in particular to a process for the purification on industrial scale of (17β)-2-methoxy-estra-1,3,5(10)-triene-3,17-diol, also known as 2- methoxyestradiol, from (17β)-4-methoxy-estra-1,3,5(10)-triene-3,17-diol, also known as 4- methoxyestradiol; the invention also refers to intermediates of such a process.

The present invention relates to a process for producing crystalline estetrol monohydrate, and particularly a certain polymorphic form thereof, comprising the steps of dissolving estetrol in an aqueous mixture comprising an alcohol to obtain a solution; cooling the solution to a cooling temperature 2; optionally, stirring the cooled solution at the cooling temperature 2; further cooling the solution to a cooling temperature 3 to form a suspension, stirring the suspension at the cooling temperature 3; and isolating crystalline estetrol monohydrate from the suspension.

Among the various aspects of the present disclosure is the provision of neuroactive steroid compositions and methods of use thereof. Disclosed herein are neuroactive steroid compositions that inhibit a voltage-gated calcium ion channel for use in the treatment of pain. Methods to treat pain that includes administering a neuroactive steroid composition to a subject in need is also disclosed.

The present invention relates to a process for the production of (15α,16α,17β)-estra-1,3,5(10)-triene-3,15,16,17-tetrol monohydrate, also known as estetrol monohydrate, having the following formula:

Provided herein are 19-nor C3,3-disubstituted C21-pyrazolyl steroids of Formula (I): and pharmaceutically acceptable salts thereof, wherein - - - - -, R1, R2, R3a, R3b, R4a , R4b, R5, R6, and R7 are as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and / or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and / or withdrawal syndromes, and tinnitus.

The present invention relates to a process for preparing (15α,16α,17β)-estra-1,3,5(10)-triene- 3,15,16,17-tetrol monohydrate, also known as Estetrol monohydrate, having formula (I).