99results about "Estrane derivatives" patented technology

Certain benzopyran antiestrogens are disclosed for treating estrogen sensitive diseases such as breast cancer. Prodrug forms provide ease of manufacturing, good shelf life, and bioavailability, and preferred stereoisomers are shown to be more effective than racemic mixtures.

Methods of using 7α,11β-dimethyl-17β-hydroxyestra-4,14-dien-3-one (III)

and 17 esters thereof for various hormonal therapies, oral and parenteral dosage forms comprising these actives, and processes for their preparation.

Methods for treating sex steroid-dependent diseases by inhibiting sex steroid activity include administration of novel compounds which include an androgenic nucleus substituted at a ring carbon with at least one substituent specified herein. Such compounds may function by inhibiting sex steroid synthesis (both estrogen and androgen synthesis) and/or by antagonistically blocking androgen receptors.

The present invention is directed to modified, hydroxy-bearing aromatic ring structures having cytoprotective activity. More specifically, in a first embodiment the present invention is directed to phenolic compounds, and in particular steriods (e.g., estrogens), wherein a non-fused polycyclic, hydrophobic substituent is attached to the hydroxy-substituted A-ring thereof. The present invention is further directed to a process for conferring cytoprotection to a population of cells involving the administration of the compound.

Disclosed are compounds of the formula:

wherein R₁, R₂, R₃ and R₄ are independently hydrogen, C₁-C₆ alkyl, halo, a sulfate, a glucuronide, —OH, a bulky group, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, —N(CH₂)_n; a phosphate group, and a phosphinate group; R₉ is hydrogen, halogen or alkyl; R₁₁ is selected from the group consisting of H, C₁-C₆ alkyl, halogen, a sulfate, a glucoronide, —SO₂NH₂, —COOH, —CN, —CH₂CN—, —NHCN—, —CHO, ═CHOCH₃, —COO salt, —OSO₂alkyl, —NH₂, and —NHCO(CH₂)_n; R₁₂ is selected from the group consisting of H, a C₁-C₆ alkyl, a sulfate, a glucoronide, a bulky group, aryl, cycloalkyl, heteroaryl and heterocycloalkyl; X is selected from the group consisting of C₁-C₁₂ alkyl, C₂-C₁₂ alkenyl, C₂-C₁₂ alkynyl, halogen, a glucoronide, —NH₂, —SO₂NH₂, —COOH, —CN, —CH₂CN, —NHCN, —CHO, —COOsalt, —OSO₂alkyl, —SH, —SCH₃, —CH[(CH₂)_nCH₂]COOCH₂, —(CH₂)_mCOOCH₃, —(CH₂)_m—O—CH₃, —(CH₂)_m—O—(CH₂)_nCH₃, (CH₂)_m—S—CH₃, —(CH₂)_m—S—(CH₂)_nCH₃, —(CH₂)_m—NH—(CH₂)_nCH₃, —C₂-C₈ alkenyl-O—(CH₂)_nCH₃, —C₂-C₈ alkenyl-S—(CH₂)_nCH₃, —C₂-C₈ alkenyl-N—(CH₂)_nCH₃, —C₂-C₈ alkynyl-O—(CH₂)_nCH₃, —C₂-C₈ alkynyl-S—(CH₂)_nCH₃, —C₂-C₈ alkynyl-N—(CH₂)_nCH₃, —(CH₂)_m—OH, —(CH₂)_m—O—NH₂, —(CH₂)_m—S—NH₂, —NH(CH₂)_mCH₃, —NH(CH₂)_mOCH₃, —NH(CH₂)_mCHOH—COOH, —N(CH₃)₂, —(CH₂)_m(NH)CH₂OH, —NHCOOH, —(CH₂)_mNHCOOH, —NO₂, —SCN, —SO₂alkyl, —B(OH)₂, —(CH₂)_m N(CH₃)—SO₂—NH₃, —(CH₂)_m—NH—SO₂—NH₂, —NHC(═S)CH₃, and —NHNH₂; and Y is selected from hydrogen, ═O, —OCO(R₆) and —OH; wherein m is an integer between 0-20, n is an integer between 0-8, the symbol represents either a single or a double bond capable of forming a keto group at position 3 or 17; and the symbol represents any type of bond regardless of the stereochemistry; and the respective enantiomers, other stereochemical isomers, hydrates, solvates, tautomers and pharmaceutically acceptable salts of said compounds. The compounds are useful in the treatment of various types of cancer.

Provided herein are 19-nor C3,3-disubstituted steroids of Formula (I): and pharmaceutically acceptable salts thereof; wherein, , R¹, R², R^3a, R^3b, R^4a, and R^4b are as defined herein, and A is a carbon bound substituted or unsubstituted 5- to 6-membered heteroaryl ring 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 a compound of formula (I) said process comprising the steps of: a) reacting a compound of formula (II), with an acylating or a silylating agent to produce a compound of formula (III), wherein P¹ and P² are each independently a protecting group selected from R²⁻Si—R³R⁴, or R¹CO—, wherein R¹ is a group selected from C_1-6alkyl or C_3-6cycloalkyl, each group being optionally substituted by one or more substituents independently selected from fluoro or C_1-4alkyl; R², R³ and R⁴ are each independently a group selected from C_1-6alkyl or phenyl, each group being optionally substituted by one or more substituents independently selected from fluoro or C_1-4alkyl; b) reacting the compound of formula (III) in the presence of palladium acetate or a derivative thereof to produce compound of formula (IV); and c) reacting the compound of formula (IV) with a reducing agent to produce compound of formula (I).

The present invention relates to a process for the preparation of estra-1,3,5(10)-trien-3,15α,16α,17β-tetraol (estetrol), via a silyl enol ether derivative 17-B-oxy-3-A-oxy-estra-1,3,5(10),16-tetraene, wherein A is a protecting group and B is —Si(R²)₃. The invention further relates to a process for the synthesis of 3-A-oxy-estra-1,3,5(10),15-tetraen-17-one, wherein A is a protecting group, via said silyl enol ether derivative.

A process is provided for the making of estetrol starting from a 3-A-oxy-estra 1,3,5(10),15-tetraen-17-one, wherein A is a C₁-C₅ alkyl group, preferably a methyl group, or a C₇-C₁₂ benzylic group, preferably a benzyl group. This process is particularly suitable to industry.

The present invention relates to a process for the preparation of a compound of formula (I) comprising the steps of a) reacting a compound of formula (II) with a silylating or an acylating agent to produce compound of formula (III), wherein P¹ is a protecting group selected from R²Si—R³R⁴ or R¹CO—, R¹ is a group selected from C_1-6alkyl or C_3-6cycloalkyl, each group being optionally substituted by one or more substituents independently selected from fluoro or C_1-4alkyl; R², R³ and R⁴ are each independently a group selected from C_1-6alkyl or phenyl, each group being optionally substituted by one or more substituents independently selected from fluoro or C_1-4alkyl; b) halogenation or sulfinylation of the compound of formula (III) to produce a compound of formula (IV); wherein X is halo, or —O—SO—R⁵, and R⁵ is a group selected from C_6-10aryl or heteroaryl, each group being optionally substituted by one or more substituents independently selected from chloro or C_1-4alkyl; c) dehalogenation or desulfinylation of the compound of formula (IV) to produce compound of formula (V); and d) reacting the compound of formula (V) with a reducing agent to produce compound of formula (I).

The present disclosure relates to the methods for the preparation of reactive [F-18]fluoride in a form of [F-18]sulfonyl fluoride suitable for efficient radiolabeling without an azeotropic evaporation step by the use of anion exchange resin and sulfonyl chloride, and its applications in the manufacturing of PET radiopharmaceuticals.

The invention discloses a method for preparing estradiol ultrafine particles with a supercritical anti-solvent technology. The method comprises the steps as follows: step S1, estradiol is dissolved in an organic solvent, and an estradiol solution is prepared; step S2, CO2 is introduced into a crystallization kettle, and the temperature and pressure in the crystallization kettle are adjusted; step S3, CO2 is introduced continuously at a constant flow rate, and the estradiol solution prepared in step S1 is introduced into the crystallization kettle while the temperature and pressure in the crystallization kettle are kept unchanged; Step S4, CO2 is introduced continuously after the introduction of estradiol solution, the temperature and pressure in the crystallization kettle are kept unchanged, the pressure is relieved after a period of time, and after the pressure in the crystallization kettle is reduced to atmospheric pressure, the crystallization kettle is opened for collecting the estradiol ultrafine particles, wherein the sequence of the step S1 and the step S2 can be changed, and the organic solvent is a mixed solvent of acetone and ethanol. With the adoption of the method, estradiol with fine particle size can be prepared, the solubility of estradiol in water is improved, and accordingly, the bioavailability of estradiol is improved.

The present invention relates to analogs of estradiol, which, in their most preferred embodiment, act as locally active estrogens without significant systemic action. A series of 16alpha-carboxylic acid substituted steroids and their esters is presented which exhibit excellent biological activity for use in pharmaceutical compositions for the treatment of symptomology associated with menopause. The present invention is therefore directed to compounds according to the structure: Where R is H, a C1 to C5 alkyl, vinyl, CF3, CH2CH2F, CH2CHF2 or CH2CF3; and m is from 0-2, or a pharmaceutically acceptable salt thereof. Preferably, R is methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl, pentyl, neo-pentyl, vinyl, CF3, CH2CH2F, CH2CHF2 or CH2CF3 and m is 0. More preferably, R is methyl, ethyl, CH2CH2F, CH2CHF2 or CH2CF3 and m is 0.

The present invention relates to a method for synthesizing a radiopharmaceutical using a cartridge, which makes it possible to carry out several steps of reaction required for synthesizing a radiopharmaceutical in the cartridge filled with a polymer. A method for synthesizing a radiopharmaceutical according to the present invention enables each step's reaction to be carried out with the solution confined in the cartridge so as not to flow out, thus being simplified compared to the conventional methods for synthesizing radiopharmaceuticals, and expediting the synthesis thereof.

The invention discloses a compound, a conjugate, a kit for detecting estradiol, and an application of the kit for detecting the estradiol in detection of the estradiol. The compound has a structure shown as a formula (1), wherein the L represents a connecting arm, the R<1>, R<2>, R<3> and R<4> are respectively independently a hydrogen group, a hydroxyl group, an alkyl of C<1-3>, an alkoxy of C<1-3>, an alkenyl of C<2-3> or an alkynyl of C<2-3>. The compound disclosed by the invention can be used for accurately detecting estradiol.

The invention discloses a method for extracting steroid hormone from excrement of forest musk deer. The method comprises the following step of leaching animal excrement by virtue of extraction liquid so as to obtain leaching liquid containing the steroid hormone, wherein the extraction liquid is an ethanol water solution, a methanol water solution, ethanol or methanol; the concentration of volume percent of ethanol in the ethanol water solution is more than or equal to 60% and less than 100%; the concentration of volume percent of methanol in the methanol water solution is more than or equal to 60% and less than 100%; the steroid hormone is one or two or all of cortisol, estradiol and testosterone. An experiment proves that the steroid hormone is extracted from the excrement of the forest musk deer by virtue of the extraction method, the optimal extraction liquid is 90E (10% ethanol water solution).