663 results about "Racemization" patented technology

A fused ring compound, a pharmaceutical composition comprising same, and the use thereof. The compound has a structure as represented by formula (I), or is a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer or a mixture form thereof, a metabolite, a metabolic precursor, an isotope-substituted form, a pharmaceutically acceptable salt, a hydrate, a solvate, a polymorph or a co-crystal thereof. The compound can be used for treating one or more cancers caused by KRAS mutation.

A fused ring compound, a pharmaceutical composition comprising same, and a use. The compound has a structure represented by formula (I) or a tautomer, mesomere, racemate, enantiomer, diastereomer or mixture thereof, metabolite, metabolic precursor, isotope substitution form, pharmaceutically acceptable salt, hydrate, solvate, polymorph or eutectic thereof. The compound can be used for treating a cancer caused by KRAS mutations, and said cancer is selected from one or more cancers caused by KRAS G12C, KRAS G12V, KRAS G12A and G12D mutations. In particular, the compound can serve as a G12D inhibitor and has relatively high inhibitory activity.

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 application relates to a multi-specific bioconjugate linker and a method for synthesizing the same, and specifically to a compound or its tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt thereof. The present application also relates to a method for preparing the compound and its use in tumor treatment.

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.

The invention provides a compound as shown in a formula (I) and a racemate, a stereoisomer, a tautomer, an isotope label, a nitrogen oxide, a solvate, a polymorphic substance, a metabolite, ester, a prodrug or pharmaceutically acceptable salt thereof, which have better BRD4 inhibition and degradation effects as a drug, and can be used for preparing drugs related to BRD4 inhibition and degradation. And preventing and / or treating related diseases. # imgabs0 #

The invention relates to the technical field of chemical synthesis, and particularly provides a preparation method of a semaglutide side chain, which comprises the following steps: step S1, carrying out reaction on octadecanedioic acid mono-tert-butyl ester and trifluoroacetic acid pentafluorophenyl ester to generate a first intermediate; s2, enabling the first intermediate to react with 1-tert-butyl L-glutamic acid to generate a second intermediate; s3, enabling the second intermediate to react with pentafluorophenyl trifluoroacetate to generate a third intermediate; and S4, carrying out an amidation reaction on the third intermediate and 17-amino-10-oxo-3, 6, 12, 15-tetraoxa-9-aza-heptadecanoic acid, so as to generate a semaglutide side chain, and carrying out an amidation reaction on the third intermediate and 17-amino-10-oxo-3, 6, 12, 15-tetraoxa-9-aza-heptadecanoic acid. According to the preparation method disclosed by the embodiment of the invention, the pentafluorophenyl trifluoroacetate is used as the condensation reagent for two times to activate the carboxylic acid, and the amidation reaction is carried out for two times to construct the amido bond after each activation, so that compared with the traditional carbodiimide and urea positive ion type condensation reagent, the chiral racemization in the condensation process can be effectively avoided, and the yield of the product is improved. The condensation chiral racemization impurity can be lower than 0.3%.

The invention belongs to the field of biological pharmacy and biological conversion, and particularly relates to a lipase mutant and application thereof. The lipase CALB mutant disclosed by the invention is obtained by carrying out single-point mutation or combined mutation on the 40th site, the 134 site, the 154 site, the 189th site, the 278th site and the 281 site of an amino acid sequence as shown in SEQ ID NO.1. Compared with a wild type, the mutant has the advantage that the stereoselectivity is greatly improved when the mutant is used for catalyzing racemization 3-cyclohexene-1-methyl formate to produce (S)-3-cyclohexene-1-formic acid. Compared with a traditional chemical method for preparing (S)-3-cyclohexene-1-formic acid, the lipase CALB mutant provided by the invention is high in stereoselectivity, mild in reaction condition, environment-friendly, low in equipment requirement, capable of greatly reducing the production cost and wide in application prospect in industrial application.

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.

The invention discloses cyclohexene formate esterase, a mutant of cyclohexene formate esterase and application of cyclohexene formate esterase in production of (S)-3-cyclohexene-1-formic acid. According to the cyclohexene formate esterase and the mutant disclosed by the invention, 100-400g / L of racemic 3-cyclohexene-1-methyl formate can be split by taking wet thalli subjected to induced expression or crude enzyme liquid obtained by ultrasonically crushing the wet thalli as a catalyst, so that (S)-3-cyclohexene-1-formic acid with chemical purity and optical purity reaching 99% or above is synthesized. The enzyme activity of the cyclohexene formate esterase mutant provided by the invention is further improved, the reaction time and the catalyst dosage are obviously reduced compared with those of a substrate with the same catalysis concentration before mutation, the reaction condition is mild, the operation is relatively simple and convenient, and the cyclohexene formate esterase mutant has a very good industrial application prospect.

The synthesis method comprises the following steps: firstly, respectively synthesizing a fragment I (1-13), a fragment II (14-21) and a fragment III (22-39), then synthesizing a fragment (14-39) in a liquid phase by using the fragment II (14-21) and the fragment III (22-39), and finally, condensing, cracking and purifying the fragment I (1-13) and the fragment (14-39) in the liquid phase to prepare the tilpotide. According to the invention, synthesis is carried out through three fragments, so that the synthesis steps are simplified, the racemization problem is avoided, + / -Gly impurities are reduced, and DKP side reaction is avoided and reduced, thereby improving the whole yield.

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)

The present invention discloses a method for synthesizing rasagiline in a microfluidic field. The method is based on a double enzyme hydrogenation cascade reaction, which efficiently converts racemic alcohol into enantiomeric amines, realizes the direct synthesis of chiral amines, and has high atom economy and reaction efficiency. Racemic 1-indanol is completely oxidized to generate 1-indanone by alcohol dehydrogenase catalysis, and the cofactor NADP+ is reduced to NADPH to provide the required reducing power for subsequent reactions; using ( R )-selective reductive amino enzyme catalyzes the reductive amination reaction of 1-indanone to generate the target product rasagiline. The present invention adopts a dual enzyme synergistic catalytic strategy to successfully achieve the efficient conversion from racemic alcohol to chiral amine, has the advantages of mild reaction conditions, green sustainability, high product yield and optical purity, and provides a new efficient, economical and environmentally friendly way for the synthesis of rasagiline.

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.

A compound as shown in formula (I) and a racemate, a stereoisomer, a tautomer, an isotopic label, a nitrogen oxide, a solvate, a polymorph, a metabolite, an ester, a prodrug or a pharmaceutically acceptable salt thereof. Such a compound has a good inhibitory effect on FGFR2 and / or FGFR3, can be used for treating or preventing conditions and diseases mediated by FGFR2 and / or FGFR3, and can be used in the preparation of a drug for treating or preventing such conditions and diseases.

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.

The invention provides an oxime-containing compound and application thereof. The oxime-containing compound provided by the invention has a structure as shown in a formula (I) or enantiomers, diastereoisomers, racemate, tautomers, stereoisomers, geometric isomers, nitrogen oxides, metabolites or pharmaceutically acceptable salts, esters, solvates, hydrates, isotope labeled compounds or prodrugs of the structure as shown in the formula (I). The oxime-containing compound provided by the invention can be used for preventing and / or treating cancers and other hyperproliferative diseases and diseases related to Hippo pathway dysfunction. # imgabs0 #

The present invention relates to novel compounds of general formula (1), their suitable pharmaceutically acceptable salts, their solvates, their hydrates, their stereoisomers, their polymorphs, their racemic mixtures, their optically active forms and their use in the treatment of inflammatory conditions such as psoriasis, asthma, psoriatic arthritis or rheumatoid arthritis. Further, the present invention relates to processes of preparing such compounds, novel intermediates involved in their synthesis.

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 application relates to novel compounds of formula (I), or a detectably labelled compound, stereoisomer, racemic mixture, pharmaceutically acceptable salt, hydrate, or solvate thereof, that can be employed in the imaging of alpha-synuclein aggregates and determining an amount thereof. Furthermore, the compounds can be used for diagnosing a disease, disorder or abnormality associated with an alpha-synuclein aggregates (such as Parkinson's disease or such as multiple system atrophy (MSA)), determining a predisposition to such a disease, disorder or abnormality, prognosing such a disease, disorder or abnormality, monitoring the evolution of the disease in a patient suffering from such a disease, disorder or abnormality, monitoring the progression of such a disease, disorder or abnormality and predicting responsiveness of a patient suffering from such a disease, disorder or abnormality to a treatment thereof.

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.