535 results about "Racemization" patented technology

Compositions for inducing and maintaining a state of flow in a subject include optically pure S-beta-hydroxybutyrate or non-racemic mixtures enriched with the S-enantiomer. The S-beta-hydroxybutyrate enantiomer modulates the effect of ketone bodies in the subject and controls the rate at which ketosis is achieved. Beta-hydroxybutyric acid is more rapidly absorbed and utilized by the body than salts or esters, enhances taste, and reduces the need to include citric acid or other edible acids. Beta-hydroxybutyrate salts are more slowly absorbed and utilized by the body and can provide one or more electrolytes. Compositions for controlling ketone body level in a subject may contain a dietetically or pharmaceutically acceptable carrier and optically pure S-beta-hydroxybutyrate or non-racemic mixture enriched with S-beta-hydroxybutyrate, wherein the compositions contain from about 50.5% to 100% by enantiomeric equivalents of S-beta-hydroxybutyrate and from about 49.5% to 0% by enantiomeric equivalents of R-beta-hydroxybutyrate.

S-Beta-hydroxybutyric acid compositions for oral delivery are effective in rapidly raising blood ketone levels without causing acute acidosis or gastrointestinal (GI) distress when consumed in sufficiently dilute form and / or as a gel or suspension. By limiting added beta-hydroxybutyrate salts containing alkali or alkaline earth metal ions, beta-hydroxybutyric acid solutions, gels, or suspensions can deliver exogenous ketone bodies without significantly altering electrolyte balance. Although aqueous beta-hydroxybutyric acid solutions are moderately acidic with a pH of about 3.5 to 4, when diluted with sufficient water, the water acts as a pseudo buffering agent that offsets otherwise harsh acidic effects when consumed orally. Gels and suspensions can also ameliorate acidic effects by partially encapsulating the beta-hydroxybutyric acid. Beta-hydroxybutyric acid can be pure S-beta-hydroxybutyric acid or a non-racemic mixture enriched with S-beta-hydroxybutyric acid relative to R-beta-hydroxybutyric acid.

Compositions for inducing and maintaining a state of flow in a subject include optically pure S-beta-hydroxybutyrate or non-racemic mixtures enriched with the S-enantiomer. The S-beta-hydroxybutyrate enantiomer modulates the effect of ketone bodies in the subject and controls the rate at which ketosis is achieved. Beta-hydroxybutyric acid is more rapidly absorbed and utilized by the body than salts or esters, enhances taste, and reduces the need to include citric acid or other edible acids. Beta-hydroxybutyrate salts are more slowly absorbed and utilized by the body and can provide one or more electrolytes. Compositions for controlling ketone body level in a subject may contain a dietetically or pharmaceutically acceptable carrier and optically pure S-beta-hydroxybutyrate or non-racemic mixture enriched with S-beta-hydroxybutyrate, wherein the compositions contain from about 50.5% to 100% by enantiomeric equivalents of S-beta-hydroxybutyrate and from about 49.5% to 0% by enantiomeric equivalents of R-beta-hydroxybutyrate.

The present invention relates to the field of medicine, and in particular to a PRMT5 inhibitor, as well as a preparation method therefor and a use thereof. The PRMT5 inhibitor is a compound as shown in formula (I), an enantiomer, a diastereoisomer, a racemate, a solvate, a hydrate, a polymorph, a prodrug, an isotope variant, or a pharmaceutically acceptable salt thereof. The present invention has better activity, selectivity, pharmacokinetic characteristics, safety or a wider treatment window.

The invention discloses a compound as shown in a formula (I), and / or pharmaceutically acceptable salts thereof, and / or a raceme mixture, a hydrate, a solvate, a prodrug, an enantiomer, a diastereoisomer and a tautomer thereof, and belongs to the technical field of medicines. The invention also discloses a pharmaceutical composition containing the compound as shown in the formula (I), and the compound as shown in the formula (I) and / or a pharmaceutically acceptable salt thereof, and / or a racemic mixture, a hydrate, a solvate, a prodrug, an enantiomer, a diastereoisomer and a tautomer thereof, and / or the pharmaceutical composition, a pharmaceutically acceptable salt thereof, and / or a racemic mixture, a hydrate, a solvate, a prodrug, an enantiomer, a diastereoisomer and a tautomer thereof. The invention further discloses application of the cGAS agonist in preparation of the cGAS agonist and a medicament for treating diseases responding to activation of the cGAS-STING signal channel.

The invention provides a preparation method of an efficient selective antagonist BQ-788, and relates to the technical field of preparation of antagonists. A solid-liquid combination method is adopted for synthesis, due to the fact that dimethyl dialkanoate on a side chain of tryptophan (DTrp) is difficult, Fmoc-DTrp (CO2Me)-OH is obtained through liquid-phase synthesis, p-methoxybenzyl is selected for protecting carboxyl in the synthesis process, the carboxyl can be removed through trifluoroacetic acid subsequently, and the risk that an indole ring of tryptophan is reduced due to hydrogenation can be successfully avoided. According to the present invention, by using the solid phase synthesis method, the fragment can be rapidly and efficiently obtained, the racemization problem during the condensation process can be effectively avoided, the urea is formed on the solid phase, the operation is simple and convenient, the hydrogen and the diphosgene are not used during the preparation process, the production is safe, the obtained product has characteristics of high yield and high purity, and the preparation steps are less.

An HPK1 degradation agent and use thereof in the field of medicine. The invention specifically relates to a compound as shown in a general formula (I) or a stereoisomer, a racemate, a tautomer, a deuterated substance, a solvate, a prodrug, a metabolite, a pharmaceutically acceptable salt or eutectic thereof, and an intermediate thereof, and the use thereof in inhibiting or degrading HPK1-related diseases such as cancer. B-L-K (I)

An aqueous pharmaceutical composition including compound having the formula of tetragadolinium [4,10-bis(carboxylatomethyl)-7-{-3,6,12,15-tetraoxo-16-[4,7,10-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis({[({2-[4,7,10-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino)acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate wherein the stereochemistry at the chiral carbon of the four alanine substituents is selected from the group consisting of RRRR, SSSS, RSSS, RRSS, and RRRS stereoisomers, and racemic and diastereomeric mixtures of any thereof, or a tautomer, a hydrate, a solvate, or a salt thereof, or a mixture of same is described. The compounds may be used as an MRI contrast imaging agent.

The present invention belongs to the technical field of pharmaceutical synthesis, and particularly relates to a method for efficiently preparing triptorelin acetate. The present invention adopts a fragment condensation method combining solid phase and liquid phase, prepares fragments 1-7 by solid phase method, prepares fragments 8-10 by liquid phase method, then condenses fragments 1-7 and fragments 8-10 by solid phase method to obtain triptorelin 10-peptide resin, and finally cleaves the resin and purifies it to obtain triptorelin acetate. This method can effectively avoid the racemization of His and Pyr, significantly reduce the D-His2-triptorelin impurity, and obtain triptorelin acetate with a purity of more than 99.9% at a total yield of up to 65%.

The invention relates to a synthetic method of a finelrenone racemate, which comprises the following steps: carrying out Knoevenagel condensation, Hantzsch dihydropyridine synthesis, O-ethylation and deprotection four-step reaction, selecting a compound shown as a formula (2) and a compound shown as a formula (3) as initial raw materials, and carrying out Knoevenagel condensation reaction under the combined action of organic alkali and organic acid to synthesize a compound shown as a formula (4); carrying out Hantzsch reaction on the compound in the formula (4) and a compound in a formula (5) to synthesize a compound in a formula (6); carrying out O-ethylation reaction on the compound shown in the formula (6) and an ethylation reagent under the catalysis of acid to synthesize a compound shown in a formula (7); finally, 2, 4-dimethoxybenzyl is removed from the compound shown in the formula (7) under the promotion of acid to synthesize the finerenone racemate, the method is high in selectivity and simple in post-treatment, the yield and purity of the product are high, the HPLC purity can reach 99% or above, a new synthesis route and method are developed for synthesizing the finerenone racemate, and the method has good application potential and research value.

The invention discloses an enzyme catalysis preparation method of a milobalin intermediate. According to the method, racemization 3-ethyl bicyclo [3.2. 0] hept-3-ene-6-ketone is used as a substrate, specific ketoreductase is used as a catalyst, (1S, 5R)-3-ethyl bicyclo [3.2. 0] hept-3-ene-6-ketone is selectively reduced into (1S, 5R)-3-ethyl bicyclo [3.2. 0] hept-3-ene-6-alcohol, and a target compound milobalin intermediate (1R, 5S)-3-ethyl bicyclo [3.2. 0] hept-3-ene-6-ketone is reserved. According to the method disclosed by the invention, only one enzyme is used, the concentration of a conversion substrate can reach 200g / L, the yield can reach 47.4%, the ee value can reach 99.8%, the operation is simple, the resolution efficiency is high, the selectivity is good, and the method can be used for industrial production.

Provided in the present application is a compound represented by formula (I), or an enantiomer, a diastereoisomer, a racemate, a tautomer, a stereoisomer, a geometric isomer, a nitrogen oxide, a metabolite or a pharmaceutically acceptable salt, an ester, a solvate, a hydrate, an isotope-labeled compound or a prodrug thereof. The compound represented by formula (I) of the present application has a relatively ideal inhibitory activity with regard to KAT6A and / or KAT6B.

Compounds are provided having the structure of Formula (I) or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein R1, R2, X1, X2, Y1, and Y2 are as defined herein. Such compounds function as thyromimetics and have utility for treating diseases such as neurodegenerative disorders and fibrotic diseases. Pharmaceutical compositions containing such compounds are also provided, as are methods of their use and preparation.

Provided in the present invention is a small molecule compound, which is characterized in that it is a compound or a stereoisomer, geometric isomer, tautomer, racemate, hydrate, solvate, metabolite, and pharmaceutically acceptable salt or prodrug of the compound as represented by the following structural formula: formula (I). The small molecule compound of the present invention is applicable as a highly efficient and specific JAK kinase inhibitor, specifically a Tyk2 inhibitor and / or a JAK1 inhibitor, and / or a JAK1 / Tyk2 dual inhibitor.

The invention relates to a pyrimidine derivative as well as a pharmaceutical composition and application thereof, and particularly provides a compound as shown in the following formula H, and a raceme, a stereoisomer, a tautomer, an isotope label, a solvate, a polymorphic substance, a metabolite, a pharmaceutically acceptable salt or a prodrug of the compound.

The invention relates to the field of chemistry or medicinal chemistry, in particular to a synthesis method of isoxazoline anti-parasitic drug lotirasodium. The synthesis method comprises the following steps: firstly, synthesizing an intermediate 1 (1, 2, 3-trichloro-5-(1-trifluoromethyl-vinyl) benzene); then synthesizing an intermediate 2 (5-bromo-4-methyl-2-thiophenecarboxime); the preparation method comprises the following steps: carrying out a 1, 3 dipolar cycloaddition reaction on an intermediate 1 and an intermediate 2 in sequence to obtain an intermediate 3, carrying out a Grignard reaction to obtain racemic acid, and finally carrying out chemical resolution and amide condensation in sequence to obtain lotirasodium. According to the novel synthesis method of the isoxazoline anti-parasitic drug lotirazine, wittig reaction is adopted for the first time to obtain the intermediate 1, operation is simpler and more convenient, and reaction conditions are mild. Besides, the synthesis method of the intermediate 2 is improved, so that the reaction conditions are milder, the operation is simpler, the cost is greatly reduced on the basis of reported reaction conditions, and the method is suitable for industrialization.

The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method and application of 3-aminopyrrolidine-1-carboxylic acid tert-butyl ester. According to the preparation method, cheap (R)-1-carboxylic acid tert-butyl ester-3-hydroxypyrrolidine is taken as a raw material, a racemic compound 5 is obtained through a two-step reaction under the action of substituted sulfonyl chloride, and racemic 3-aminopyrrolidine-1-carboxylic acid tert-butyl ester is obtained through a hydrazinolysis reaction. The preparation method provided by the invention is simple and convenient to operate, the production safety is remarkably improved, the purity and yield of the obtained target product can be further improved, and industrial production is facilitated. In addition, the invention also provides a method for preparing racemic 3-aminopyrrolidine-1-carboxylic acid tert-butyl ester by using the obtained 3-aminopyrrolidine-1-carboxylic acid tert-butyl ester.

The invention provides a method for synthesizing N-methylated polypeptide, which comprises the following steps: dissolving a carboxylic acid compound, N-methyl amino-acid ester hydrochloride or N-methyl amino-acid ester, an alkaline substance and pivaloic anhydride in an organic solvent, reacting at 15-80 DEG C for 3-10 hours, and post-treating the obtained reaction liquid to obtain an N-methyl dipeptide compound, the method comprises the following steps: removing a protecting group in an N-methyl dipeptide compound to obtain a free-state N-methyl dipeptide compound, and condensing the free-state N-methyl dipeptide compound and amino acid or N-methyl amino-acid ester protected by amino to obtain the N-methylated polypeptide, the mixed anhydride intermediate is formed in situ, and the reaction is completed in one step; according to the method, trimethylacetic anhydride is used as a condensing agent, the structure is simple, the reaction is safe, cheap and non-toxic, a large amount of nitrogen-containing byproducts are not generated in the reaction, and purification is convenient; the method is high in stereoselectivity, and racemization is avoided; according to the method, environment-friendly solvents such as ethyl acetate can be used, the reaction condition is mild, and the reaction time is short.

The invention relates to the technical field of luminescent materials, in particular to a circularly polarized phosphorescent Pt (II) complex as well as a preparation method and application thereof. The circularly polarized phosphorescent Pt (II) complex has a structure as shown in a formula (R)-I, a formula (S)-I, a formula (R)-II, a formula (S)-II, a formula (R)-III or a formula (S)-III, according to the invention, [2.2] paracyclophane is mainly used as a planar chiral skeleton, and different sites of the planar chiral skeleton are modified to obtain the circularly polarized phosphorescent Pt (II) complex which is stable in chirality and is not easy to racemize. The high-efficiency circularly polarized phosphorescent Pt (II) complex with both luminous quantum yield and circular polarization property is obtained by utilizing the advantages of a four-coordinate plane structure, high exciton utilization rate and adjustable color of the Pt (II) complex, and the high-efficiency circularly polarized phosphorescent Pt (II) complex has great research value on development of circularly polarized chiral materials. .

A specific topoisomerase inhibitor, a use as an antibody drug conjugate, and a preparation method therefor, which relate to the technical field of medicinal chemistry. The inhibitor is a compound A or a tautomer, a mesomer, a racemate, an optical antipode, a diastereoisomer, or a mixture form thereof, or a pharmaceutically acceptable salt thereof; the structure of the compound A is such that the compound may also be further prepared to obtain an antibody drug conjugate, the antibody drug conjugate has good solubility and pharmaceutical properties, and the conjugation process does not result in precipitation, the antibody drug conjugate exhibits obvious in-vivo anti-tumor activity, and shows markedly stronger anti-tumor activity when compared with a control sample.

The present invention relates to a tetracyclic compound and a use thereof. Specifically, the present invention provides a use of a compound of formula I, or an optical isomer, a racemate, a solvate, a pharmaceutically acceptable salt, or a deuterated compound thereof in the preparation of a composition or a formulation for preventing and / or treating tumors. The compound of the present invention has an excellent precise treatment effect on tumors with low or no expression and low or no activity of mitochondrial membrane permeability pores, low or no expression and low or no activity of recombinant peptidylprolyl isomerase F, low or no expression of NNMT gene, high expression of DNA methylases, high expression of UHRF 1, a high methylation level at a nucleotide site of the NNMT gene, and / or a high methylation level at a DNA CpG site of a NNMT gene region.

The present invention belongs to the field of drug splitting technology, and in particular to a method for splitting ofloxacin chiral drugs by two-phase identification extraction. The present invention mixes ofloxacin racemate, cyclodextrin and water to obtain ofloxacin racemate aqueous phase solution; Cyclodextrin includes β-cyclodextrin and / hydroxypropyl β-cyclodextrin, and the mass concentration of cyclodextrin in ofloxacin racemate aqueous phase solution is 0.005~0.015g / mL; Tartaric acid and organic solvent are mixed to obtain organic phase solution; Tartaric acid includes L / D-di-p-methylbenzoyltartaric acid, L / D-dibenzoyltartaric acid and L / D-diethyl tartrate; Ofloxacin racemate aqueous phase solution and organic phase solution are mixed, and the obtained mixed solution is subjected to chiral extraction. The splitting method provided by the present invention not only has higher selectivity, and low cost, is suitable for industrial application.

The present invention provides a compound as a PAK4 inhibitor, having a structure as shown in Formula I or its tautomer, mesomer, racemate, enantiomer, diastereomer or mixture thereof, pharmaceutically acceptable hydrate, solvate or salt. The test results show that the compound prepared by the present invention has high inhibitory activity and selectivity for PAK4 kinase, and its liver microsome stability and rat PK are also improved to a certain extent.

Disclosed is a method for preparing (S)-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid and derivatives thereof, comprising: taking a racemate of a compound represented by Formula (I) or a racemate of a salt of the compound represented by Formula (I) as a substrate, and making a R-isomer of the compound represented by Formula (I) in the substrate react under the catalysis of oxidative dehydrogenase to generate imino acid represented by formula (II); and converting the imino acid represented by Formula (II) into an S-isomer of the compound represented by Formula (I) in the presence of pipecolic acid reductase and a coenzyme capable of supplying hydrogen anions. The process has mild reaction conditions, strong stereoselectivity, high reaction efficiency, and high conversion rate.

The present application relates to the technical field of organic synthesis, and particularly relates to a method for preparing (+)-crispine A by means of biological enzyme resolution. First, 6,7-dimethoxy-3,4-dihydroisoquinoline-2-oxide is subjected to 1,3-dipolar cycloaddition with allyl alcohol to obtain a first compound; then the first compound is added into a sulfonylation reagent and zinc powder to obtain a racemate second compound through a three-step continuous series reaction of primary alcohol sulfonylation, nitrogen-oxygen bond cleavage and ring formation; then the second compound is mixed with vinyl acetate and biological enzyme, and chiral resolution is carried out under the action of the biological enzyme to obtain a third compound with right-handed optical rotation and a fourth compound with left-handed optical rotation; finally, the third compound is mixed with an alkaline reagent and a sulfonylation reagent, and then secondary alcohol sulfonylation is carried out to obtain a fifth compound with right-handed optical rotation; the fifth compound is mixed with a deoxidizing reagent to carry out deoxidation reaction, and (+)-crispine A is prepared. The method is simple, green and environmentally friendly, and can be produced in large quantities.

The present invention discloses a method for converting a chiral compound racemate into a single enantiomer, combining crystallization and SMB processes, while reducing the separation purity requirements of SMB, respectively, the chiral substance solution at the SMB extraction port and the raffinate port is crystallized and purified, and in addition, an equal mixture of the racemate raw material, the product of the racemization reaction of the single enantiomer derived from the non-target product in the racemization reactor, and the eutectic generated by the two crystallizers is used as the three sources of the racemate at the SMB feed port, which can not only ensure the purity of the target product, but also achieve high utilization of the racemate raw material and high yield of the target product, while significantly improving the overall equipment yield. It can be seen that using the method of the present invention, the chiral compound racemate can be converted into a single enantiomer, which can significantly improve the overall equipment yield while ensuring the purity and yield of the target product.

The present invention relates to an anti-tumor use of a phosphorus compound. Specifically, the present invention provides a use of a compound of formula (I), an optical isomer thereof, a racemate thereof, a solvate thereof, a pharmaceutically acceptable salt thereof or a deuterated compound thereof in preparation of a composition or a preparation, wherein the composition or the preparation is used for preventing and / or treating tumors. The compound of the present invention exhibits excellent precise therapeutic efficacy against tumors characterized by high expression of kinase B.

The present invention discloses biphenyloxadiazole ether derivatives as immune checkpoint inhibitors capable of blocking the PD-1 / PD-L1 signaling pathway, as well as their preparation methods and uses. These compounds, as shown in Formula I below, can modulate the PD-1 / PD-L1 signaling pathway to treat a variety of related tumor diseases through tumor immunotherapy, demonstrating potential drug development. The biphenyloxadiazole ether derivatives of the present invention, or their pharmaceutically acceptable salts, racemates, optical isomers, or solvates, are also disclosed. #imgabs0#