81 results about "Pregnanetriolone" patented technology

Compounds having the structure of formula I are provided. In formula I, R1 is H, OH, substituted or unsubstituted C1 to C3 alkyl, C1 to C3 perfluoroalkyl, or COR6; R6 is H, substituted or unsubstituted C1 to C4 alkyl, aryl, substituted or unsubstituted C1 to C4 alkoxy, substituted or unsubstituted C1 to C3 aminoalkyl; R2 and R3 are H, substituted or unsubstituted C1 to C6 alkyl, C1 to C6 perfluoroalkyl, substituted or unsubstituted C2 to C6 alkenyl, substituted or unsubstituted C2 to C6 alkynyl, substituted or unsubstituted C3 to C6 cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclic; or R2 and R3 are fused to form spirocyclic rings; R4 is NHR7, OR7, NHSO2R7, or OSO2R7; Q is O, S, NR8, or CR9R10; or a pharmaceutically acceptable salt, ester, or prodrug thereof. Such compounds are useful as progesterone receptor modulators and for treating progesterone receptor related conditions.

The present invention relates, inter alia, to compounds having the general formula: in which: R1 is a member selected from the group consisting of —OCH3, —SCH3, —N(CH3)2, —NHCH3, —NC4H8, —NC5H10, —NC4H8O, —CHO, —CH(OH)CH3, —C(O)CH3, —O(CH2)2N(CH3)2, and —O(CH2)2NC5H10; R2 is a member selected from the group consisting of hydrogen, halogen, alkyl, acyl, hydroxy, alkoxy (e.g., methoxy, ethoxy, vinyloxy, ethynyloxy, cyclopropyloxy, etc.), acyloxy (e.g., acetoxy, glycinate, etc.), alkylcarbonate, cypionyloxy, S-alkyl, —SCN, S-acyl and —OC(O)R6, wherein R6 is a functional group including, but not limited to, alkyl (e.g., methyl, ethyl, etc.), alkoxy ester (e.g., —CH2OCH3) and alkoxy (—OCH3); R3 is a member selected from the group consisting of alkyl, hydroxy, alkoxy and acyloxy; R4 is a member selected from the group consisting of hydrogen and alkyl; and X is a member selected from the group consisting of ═O and ═N—OR5, wherein R5 is a member selected from the group consisting of hydrogen and alkyl.In addition to providing the compounds of Formula I, the present invention provides methods wherein the compounds of Formula I are advantageously used, inter alia, to antagonize endogenous progesterone; to induce menses; to treat endometriosis; to treat dysmenorrhea; to treat endocrine hormone-dependent tumors; to treat meningiomas; to treat uterine leiomyomas; to treat uterine fibroids; to inhibit uterine endometrial proliferation; to induce cervical ripening; to induce labor; and for contraception.

This invention relates to a galenical gel formulation for nasal administration of neurotransmitters / neuromodulators such as dopamine, serotonin or pregnenolone and progesterone. The special lipophilic or partly lipophilic system of the invention leads to high bioavailability of the active ingredient in plasma and brain caused by sustained serum levels and / or direct or partly direct transport from nose to the brain.

This invention relates to non-steroidal compounds that are modulators of androgen, glucocorticoid, mineralocorticoid, and progesterone receptors, and also to the methods for the making and use of such compounds.

This invention relates to a galenical gel formulation for nasal administration of neurotransmitters / neuromodulators such as dopamine, serotonin or pregnenolone and progesterone. The special lipophilic or partly lipophilic system of the invention leads to high bioavailability of the active ingredient in plasma and brain caused by sustained serum levels and / or direct or partly direct transport from nose to the brain.

The invention discloses a method and a kit for detecting various related substance of CAH at the same time. The method is used for detecting 17 alpha progesterone, androstenedione, 11-deoxycortisol, 21-deoxycortisol and cortisol at the same time. The method includes: (1), adding an organic solvent into a mixed internal standard product to prepare a stock solution, and diluting to obtain extractionworking liquid; (2), using the extraction working liquid to incubate a to-be-detected blood spot sample; (3), centrifuging, taking supernate, concentrating, and using 45% methanol for re-dissolving;(4), using LC-MS / MS to detect a re-dissolving product, wherein the mixed internal standard product includes isotope internal standard products of 17 alpha progesterone, androstenedione, 11-deoxycortisol, 21-deoxycortisol and cortisol. The method can quantify five hormones in one time, can provide specific, sensitive, low-false positive and high-positive-prediction-value CAH screening and can screen CAH of 11-OHD and 21-OHD at the same time, thereby improving screening efficiency and quality.

The invention discloses a preparation method of a dydrogesterone intermediate. The preparation method is characterized by comprising the following steps: dissolving 5,7-diene steroid compound in an organic solvent to obtain a solution as a raw material; and carrying out a photocatalytic reaction and separating to obtain the dydrogesterone intermediate, wherein the 5,7-diene steroid compound is 7-dehydropregnenolone acetate, pregna-5,7-diene-3,20-diketodivinyl ketal, 7-dehydropregnenolone, ergosterol or pregna-5,7-diene-3,20-diketo-3-vinyl ketal, and a lamp used in the photocatalytic reaction comprises an LED ultraviolet lamp with the wavelength range of 295-335 nm. The preparation method of the dydrogesterone intermediate is high in yield, low in cost, safer in preparation and friendlier to environment.

Applicants have discovered a method for the stereoselective and regioselective synthesis of 3α-hydroxy, 3β-methyl-5α-pregnan-20-one (ganaxolone) comprising reacting 5α-pregnane-3,20-dione; with an organometallic methylating agent in an inert solvent to provide a compound of the formula

The present invention relates to a progestogen composition. Said progestogen composition is formed from 27-31% of fluoropregestin, 2-2.7% of ethinyl estradiol, 8-10% of lauric acid, 37-40% of ethyl alcohol, 0.3-0.6% of carbomer and 6-10% of propylene glycol, and the rest is pure water. Besides, said invention also provides the delayed-release suppository device of said progestogen composition and its preparation method.

The invention relates to a method for detecting steroid hormones in blood. The method comprises the following steps: preparation of a standard curve dried blood spot sample: preparing red blood cells by using whole blood; by taking hormone-removed serum as a blank matrix, adding standard substances such as 17alpha-hydroxyprogesterone, androstenedione, cortisol, 21-deoxycortisol and 11-deoxycortisol solutions to prepare a series of serum standard curve working solutions; mixing the red blood cells with the serum standard curve working solution, and preparing a standard curve dried blood spot sample by using the obtained mixed solution; pretreatment of the dried blood spot sample: taking the dried blood spot sample, adding an internal standard-containing extraction liquid, extracting, centrifuging, drying, adding a reconstitution fluid, centrifuging, and determining by adopting liquid chromatography-tandem mass spectrometry. The detection method disclosed by the invention is simple in pretreatment operation, short in time consumption, high in stability and good in reproducibility, and various steroid isomers can be efficiently separated at the same time.

The invention relates to a method for rapidly detecting steroid hormones in urea through an UPLC-MS / MS technology, and belongs to the field of analysis chemistry and medical science. The concentrations of estriol, hydrocortisone, 17beta-estradiol, testosterone and progesterone in human urea are simultaneously detected through the UPLC-MS / MS technology by adopting a beta-glucuronidase enzymatic hydrolysis technology, the detection limit is 0.1-1.0 ng / mL, and the quantitation limit is 0.3-3.0 ng / mL. The method is fast, sensitive and accurate, can meet requirement of simultaneous detection of above five steroid hormones in urea, and has wide application prospect.

An expression cassette, operable in a recombinant host, comprising a heterologous DNA coding sequence encoding a protein, which is functional, alone or in cooperation with one or more additional proteins, of catalyzing an oxidation step in the biological pathway for conversion of cholesterol into hydrocortisone, which step is selected from the group consisting a of: the conversion of cholesterol to pregnenolone; the conversion of pregnenolone to progesterone; the conversion of progesterone to 17alpha-hydroxy-progesterone; the conversion of 17alpha-hydroxyprogesterone to cortexolone; the conversion of cortexolone to hydrocortisone, and the corresponding control sequences effective in said host.

The invention relates to an after emergency contraception medicament composition containing low-dose levonorgestrel without reducing contraceptive effect. In the medicament composition, the consumption of levonorgestrel contained by a medicament dosage unit with single-dosage medicament for emergency contraception is reduced from conventional 1.5 mg to 1.00 to 1.25 mg, and the consumption of levonorgestrel contained by the medicament dosage unit with two-dosage administration is reduced from conventional 0.75 mg to 0.50 to 0.625 mg. The composition reduces the dosage of the levonorgestrel used relative to conventional medicament dosage and reduces individual differences as well as adverse reaction, thereby having important clinical significance. The invention also provides a method for preparing the medicament composition, as well as the application of the medicament composition in the preparation of emergency contraception medicaments.

The invention relates to a pretreatment method, a detection method and a kit for simultaneously detecting multiple steroid hormones in a blood sample. The pretreatment method comprises the following steps: 1), preliminarily extracting the steroid hormone in a serum sample by using methyl tert-butyl ether; 2), performing centrifuging, taking supernatant, and carrying out sufficient alkali washing with an alkaline solution; and 3), performing centrifuging after alkali washing, taking supernate, performing freezing and blow-drying, and redissolving the obtained solid components to obtain a to-be-detected solution for simultaneously detecting various steroid hormones. According to the method, at least five steroid hormones of 17-hydroxy progesterone, androstenedione, cortisol, 21-deoxycortisoland 11-deoxycortisol can be separated at the same time, the separation effect is good, and the operation is simple and convenient.

It is an object of the present invention to obtain highly active P450scc enzyme protein which is an important enzyme protein that catalyzes the first step of the biosynthesis of industrially useful steroid hormone. The present invention provides a sterol side chain cleavage enzyme protein having the following physicochemical properties:(1) action: the enzyme acts on sterol represented by formula (I) as defined in the specification and cleaves the carbon-carbon bond between positions 20 and 22 of a sterol side chain portion by its activity of cleaving the bonds, so as to generate a compound represented by formula (II) as defined in the specification;(2) substrate specificity: when microorganisms that produce the enzyme protein are allowed to react with an aqueous solution containing 100 μg / ml 4-cholesten-3-one or cholesterol at 28° C. for 5 hours, the conversion reaction rate from 4-cholesten-3-one to progesterone is 10% or more, and the conversion rate from cholesterol to pregnenolone is 10% or more;

The invention provides didrogesterone and a preparation method thereof, which comprises the following steps: carrying out deprotection reaction on a prepared acid alcohol solution and 3, 20-bis (ethyldioxy)-9beta-10alpha-pregna-5, 7-diene, neutralizing with alkaline water, and crystallizing to obtain a deprotecting intermediate; heating and refluxing with acetic acid in a hydrophobic solvent for transposition, adding water into reaction liquid for extraction and impurity removal, collecting an oil phase, concentrating and desolventizing the oil phase under reduced pressure, and adding a hydrophilic solvent for crystallization, thereby obtaining the product didrogesterone. The preparation method provided by the invention has the advantages of single solvent, simple reaction conditions, easiness in operation, high yield of the didrogesterone, good quality and the like, and has a very good industrial application prospect.

The invention provides a novel method for synthesizing a progesterone receptor regulator, ulipristal acetate of formula I. According to the invention, the method has the advantages of ingenious conception, high yield and high purity, the cost is greatly reduced, and the method is suitable for industrial production.

The invention relates to a method for synthesizing a steroid drug dydrogesterone (CAS: 152-62-5). The method comprises the following steps: starting from pregnenolone, carrying out allylic halogenation and elimination to obtain a Pregna-5, 7-dien-3-ol-20-one intermediate; carrying out illumination isomerization to obtain a key intermediate 9 beta, 10 alpha-Pregna-5, 7-dien-3-ol-20-one; then carrying out Oppenauer oxidation (Oppenauer oxidation) to obtain 7-Dehydro-9beta, 10 alpha-progesterone, and finally, carrying out olefin shift isomerization under the action of acid to obtain the final product 6-Dehydro-9beta, 10 alpha-progesterone (a crude drug of dydrogesterone). The method is economical in steps and comprises four conversion steps; the total yield is as high as 16.4%; the raw materials are cheap and easy to obtain, the whole process route is green and safe, the bulk drugs are high in quality, the purity can reach 99.5% or above, and the method is suitable for industrial production.

The invention discloses a steroid hormone detection method that comprises the following steps: adding an internal standard substance into a sample to be detected; carrying out a derivatization reaction; detecting an analyte by using chromatography tandem mass spectrometry; the analyte comprises a first steroid hormone and a second steroid hormone at the same time; the first steroid hormone is selected from at least one of the following steroid hormones: estradiol and estriol; and the second steroid hormone is selected from at least one of the following steroid hormones: dehydroepiandrosterone,dehydroepiandrosterone sulfate, testosterone, dihydrotestosterone, androstenedione, cortisol, cortisone, 11-deoxycortisol, 17alpha-hydroxyprogesterone, 17alpha-hydroxypregnenolone, aldosterone, cortisol, deoxycortisol, progesterone and pregnenolone. The detecting method has the advantages of few operation steps and short detection time, and can specifically, sensitively, accurately and quantitatively analyze the analyte substance.

The invention relates to a noninvasive female corpus luteum function monitoring technology, in particular to a full-quantitative or semi-quantitative rapid noninvasive urine test technology for determination of cyclic production amount of progesterone metabolites in women's urine so as to monitor and evaluate a female corpus luteum function, judge different types of ovulation cycle, determine whether ovulation is really performed or not and impregnation can be achieved or not after ovulation. According to the first implementation scheme, a protein hybridized couplet for determining pregnanediol glucuronide is related and contains pregnanediol glucuronide and a coupling protein. The protein hybridized couplet is characterized by further containing a junctional complex that connects the two parts. PdG of the hormone protein couplet is detected without an unsaturated labelled antibody, the sensitivity can be up to 0.1 ng / ml, and the linear range can be controlled to be 0.1-50 ng / ml.

The present invention concerns the preparation and the therapeutic use of aqueous solutions of Progesterone or Testosterone, complexed with hydroxypropyl-3-cyclodextrin (HPβCD) that are suitable for oral administration. The solutions are characterised by a specific molar ratio between HPβCD and the hormones such as to ensure high hormone plasma levels, following oral administration, thanks to the optimisation of their solubility, permeability, metabolic stability and ultimately, bio availability. The formulation object of the present patent makes it possible to achieve effective plasma concentrations following oral administration of lower doses of hormone with respect to oral formulations currently on the market (e.g. Prometrium, Andriol) to the advantage of greater safety and compliance of the patients.

An expression cassette, operable in a recombinant host, comprising a heterologous DNA coding sequence encoding a protein, which is functional, alone or in cooperation with one or more additional proteins, of catalyzing an oxidation step in the biological pathway for conversion of cholesterol into hydrocortisone, which step is selected from the group consisting of:the conversion of cholesterol to pregnenolone;the conversion of pregnenolone to progesterone;the conversion of progesterone to 17alpha-hydroxyprogesterone;the conversion of 17alpha-hydroxyprogesterone to cortexolone;the conversion of cortexolone to hydrocortisone, and the corresponding control sequences effective in said host.

The invention provides a method and a kit for simultaneously detecting five steroid hormones and application of the method and the kit, and belongs to the technical field of steroid hormone detection. The method comprises the step of detecting a pretreated sample to be detected on the basis of LC-MS / MS (Liquid Chromatography-Mass Spectrometry / Mass Spectrometry). The pretreatment method is optimized, so that accurate detection of five steroid hormones including testosterone, androstenedione, 17alpha-hydroxyprogesterone, dihydrotestosterone and dehydroepiandrosterone sulfate is realized, and the method can be applied to detection items of important steroid hormones in clinical androstenemia. The real level of the real concentration of the five steroid hormones in the body of a subject can be given easily, clinical use or laboratory use is facilitated, and the method has important guiding significance on auxiliary diagnosis of hyperandrogenemia and polycystic ovarian syndrome and has high practical application value.

The invention discloses a preparation method and application of one group of pyrazolyl steroid derivative with antitumor activity, which belong to the technical field of medicine synthesis. The preparation method comprises the steps of generating phenylhydrazones 2 and 8 under the catalysis of isopregnenolone 1,5,16-diene progesterone and phenylhydrazine acetic acid; then carrying out ring closing reaction under the catalysis of phosphorus oxychloride to obtain compounds 3 and 9 with pyrazolyl heterocycle; then hydrolyzing to obtain compounds 4 and 10 without formyl groups; carrying out reduction with sodium borohydride to obtain 6; carrying out amination reduction reaction on the intermediate products 4 and 10 and amine under the catalysis of sodium triacetoxy borohydride to obtain 5a-e and 11a-e. The preparation method provided by the invention has the advantages of novel route, high yield and easiness for separation, and the route is an optimal route for preparing the compound.