44results about "Estrane derivatives" patented technology

The invention discloses a method for synthesizing deuterated olefin under catalysis of a palladium membrane by taking D2O as a deuterium source, and belongs to the technical field of synthesis of deuterated olefin building blocks. According to the method, a three-chamber electrolytic tank separated by a palladium membrane and an ion exchange membrane is used as a reactor, the palladium membrane is used as a working electrode, an electrolyte deuterium aqueous solution is used as an electrolyte, deuterium water is electrolyzed through a constant-potential electrolysis method, and formed active deuterium is transmitted to one side of an organic reaction taking absolute ethyl alcohol or cyclohexane as an organic solvent; and catalyzing an alkyne compound by using a palladium membrane modified by sodium thiophenol to perform reduction deuterization so as to synthesize a deuterated olefin compound with high selectivity, and further synthesizing a corresponding deuterated drug. The invention provides a green, efficient, high-universality and low-cost amplification synthesis method for synthesizing a deuterated olefin building block containing a functional group easy to reduce and hydrolyze, and the method has a wide application prospect.

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 invention relates to a process for the preparation of a compound of formula (I), its stereoisomer, salt, hydrate or solvate, which comprises the step of desulfinylating a compound of formula (II) to produce a compound of formula (I), wherein R 1 and R 2 is as defined in the claims, wherein the desulfinylation step is carried out by a continuous flow process. TIFF2025513928000072.tif62170

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.

The invention relates to a fulvestrant intermediate and a preparation method thereof. Specifically, the invention relates to a compound shown as a formula V and a preparation method thereof, and R1 is hydrogen or a hydroxyl protecting group. The invention also relates to a preparation method for the synthesis of fulvestrant from the compound as shown in the formula V. The method has the advantages of short reaction steps, mild and safe reaction conditions, high selectivity, simplicity and convenience in operation and purification, high synthesis efficiency and the like, and is suitable for large-scale production.

Object of the present invention is an improved process for the preparation of Trenbolone Acetate of formula (I): having irregular hexagon plates crystal habit, by means of crystallization of Trenbolone Acetate of formula (I) with a C2-C5 alkyl alcohol or mixture thereof.

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 relates to a process for preparing (15α,16α,17β)-estra-1,3,5(10)-triene-3,15,16,17-tetrol, also known as Estetrol, and Estetrol monohydrate, having the formulas shown below: Form

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.

According to the present application, there is provided the compound of the formula indicated herein or a pharmaceutically acceptable salt thereof in the treatment in humans of bipolar disorder, anxiety disorder, depression, tremor or tinnitus.

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).

A use of one or more lipid compounds in the delivery of nucleic acids, and a lipid nucleic acid mixture, pharmaceutical composition or kit comprising the lipid compounds and nucleic acids. The lipid compounds can promote the absorption, particularly oral absorption, of nucleic acids, and promote entry of nucleic acids into target sites in a subject in need thereof.

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 (15α,16α,17β)-estra-1,3,5(10)-triene-3,15,16,17-tetrol, also known as estetrol, and estetrol monohydrate, having the formulas shown below:

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).

To provide 19-nor C3,3-disubstituted C21-N-pyrazolyl steroids and methods of use thereof.SOLUTION: The invention provides 19-nor C3,3-disubstituted C21-pyrazolyl steroids of Formula (I) and pharmaceutically acceptable salts thereof. The compounds are expected to be 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.SELECTED DRAWING: None

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.

Object of the present invention is an improved process for the preparation of Trenbolone Acetate of formula (I) having irregular hexagon plates crystal habit and / or 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 a crystallization wherein an 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, wherein the solvent is a C2-C5 alkyl alcohol or mixture thereof.

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

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.