19851 results about "Chemical compound" patented technology

The present disclosure provides compositions and methods for using fixed biological samples in partition-based assays. In at least one embodiment, the disclosure provides a composition comprising a fixed biological sample and an un-fixing agent contained in a partition, such as a discrete droplet. In some embodiments, the disclosure provides un-fixing agent compounds capable of catalytically cleaving crosslinks in fixed biological samples, particularly crosslinked nucleic acids, such as RNA.

The present disclosure provides compositions and methods for using fixed biological samples in partition-based assays. In at least one embodiment, the disclosure provides a composition comprising a fixed biological sample and an un-fixing agent contained in a partition, such as a discrete droplet. In some embodiments, the disclosure provides un-fixing agent compounds capable of catalytically cleaving crosslinks in fixed biological samples, particularly crosslinked nucleic acids, such as RNA.

Compounds or their pharmaceutically acceptable salts can modulate the G12D mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds disclosed herein or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

Provided herein is a method or a use for treating a cancer, comprising administering to a subject a therapeutically effective amount of Compound A, a pharmaceutically acceptable salt, or a co-crystal thereof at a daily dose of 100 mg to 3600 mg on salt-free basis, wherein Compound A has the following structure:

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.

The invention belongs to the technical field of medicines, and relates to tetrahydropyridopyrimidine compounds as well as a preparation method and application thereof, in particular to tetrahydropyridopyrimidine compounds or pharmaceutically acceptable salts thereof as well as a preparation method and application thereof in preparation of antitumor drugs. The structure of the tetrahydropyridopyrimidine compound or the pharmaceutically acceptable salt thereof is as shown in a general formula (I), and R1-R4 are as shown in the specification and claims. The compound provided by the invention can be used for preparing a KRAS G12C inhibitor, is used for inhibiting G12C mutation of KRAS, has an obvious inhibiting effect on lung cancer, pancreatic cancer or colon cancer, and can be used for preparing antitumor drugs. # imgabs0 #

The invention relates to the field of medicinal chemistry, in particular to a substituted quinolinone compound targeting KRASG12D and application of the substituted quinolinone compound. Pharmacological tests prove that the affinity effect of the synthesized compound on a KRASG12D mutant is superior to that of a lead compound KAL-21404358. The compounds WY1-014 and WY1-062 have ideal inhibition effects on cells of human lung cancer (A549), human melanoma (A375) and human colon cancer (LOVO). The compound WY1-062 has excellent anti-tumor activity, and the activity of the compound WY1-062 is superior to that of cis-platinum.

The invention relates to a crystal form of a benzothiophene substituted fused ring compound and a preparation method thereof. Specifically, the invention provides a crystal form A and a crystal form D of 2-amino-7-fluoro-4-((5S, 5aS, 6S, 9R)-1-fluoro-12-((1-((4-(fluoromethylsubunit) piperidine-1-yl) methyl) cyclopropyl) methoxyl)-5-methyl-5a, 6, 7, 8, 9, 10-hexahydro-5H-4-oxa-3, 10a, 11, 13, 14-pentaaza-6, 9-methylbridged naphtho [1, 8-ab] heptano-2-yl) benzo [b] thiophene-3-formonitrile, and the crystal form A and the crystal form D have the advantages that the crystal form A and the crystal form D are good in stability; and the medicine can be better used for clinical treatment. # imgabs0 #

The invention relates to the field of medicinal chemistry, relates to a general KRAS inhibitor and medical application thereof, and particularly relates to a compound targeting KRAS and mutants KRASG12C and KRASG12D thereof and medical application of the compound. The pharmacological test result of the affinity of KRAS and mutants thereof shows that the affinity of the compound to a KRAS wild type and a KRASG12C mutant type thereof and a KRASG12D mutant type thereof is superior to that of a lead compound, and the compound has a potential inhibition effect on target spots of the KRAS wild type and the KRASG12C mutant type thereof and the KRASG12D mutant type thereof.

The invention relates to a crystal form of a benzothiophene substituted fused ring compound and a preparation method thereof. Specifically, the invention provides a crystal form E, a crystal form G and a crystal form H of 2-amino-7-fluoro-4-((5S, 5aS, 6S, 9R)-1-fluoro-12-((1-((4-(fluoromethylsubunit) piperidine-1-yl) methyl) cyclopropyl) methoxyl)-5-methyl-5a, 6, 7, 8, 9, 10-hexahydro-5H-4-oxa-3, 10a, 11, 13, 14-pentaaza-6, 9-methylbridged naphtho [1, 8-ab] heptano-2-yl) benzo [b] thiophene-3-formonitrile, and the crystal form E, the crystal form G and the crystal form H have the advantages that the stability is good; and the medicine can be better used for clinical treatment. # imgabs0 #

Provided herein are polymorphs and crystalline forms of 2-fluoro-5-((5S,5aS,6S,9R)-1-fluoro-12-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-5-methyl-5a,6,7,8,9,10-hexahydro-5H-4-oxa-3,10a,11,13,14-pentaaza-6,9-methanonaphtho[1,8-ab]heptalen-2-yl)-3-methyl-4-(trifluoromethyl)aniline (Compound of Formula (I)), pharmaceutical compositions thereof, and methods of their use, for example, in the treatment of cancer. Also provided herein are synthetic processes for the manufacture of a compound of Formula (I) (i.e., 2-fluoro-5-((5S,5aS,6S,9R)-1-fluoro-12-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-5-methyl-5a,6,7,8,9,10-hexahydro-5H-4-oxa-3,10a,11,13,14-pentaaza-6,9-methanonaphtho[1,8-ab]heptalen-2-yl)-3-methyl-4-(trifluoromethyl)aniline). Also provided are compounds useful in its synthesis (e.g., those of Formulae (A), (B), (By), and (H)) and synthetic processes directed thereto.

Provided herein is a Drug-Linker of Formula (I) or a pharmaceutically acceptable salt thereof, wherein D is a drug unit, K1 is selected from (i) a peptide unit, (ii) an oligosaccharide, and (iii) a polyether, and M1 is a group which can react with a ligand to form a connector unit. Such compounds can be useful as anti-cancer agents.

Provided is a compound useful as an active ingredient in a pharmaceutical composition for treating cancer.　The present inventors have examined a compound useful as an active ingredient in a pharmaceutical composition for cancer treatment, and have completed the present invention by finding that: a heterocyclic compound represented by formula (I) and formula (I-I) has excellent an action of inducing degradation of a mutant KRAS protein and a wild-type KRAS protein, and in particular, an action of inducing degradation of a KRAS protein having a G12C mutation, G12D mutation, G12V mutation, or G13D mutation; and said heterocyclic compound has mutant KRAS inhibition and the inhibitory activity of KRAS amplified by a wild-type KRAS gene, and in particular, inhibitory activity of KRAS having a G12C mutation, G12D mutation, G12V mutation, or G13D mutation. The heterocyclic compound according to the present invention or a salt thereof can be used as a therapeutic agent for cancer.

A compound of formula (I) or a pharmaceutically acceptable salt or hydrate thereof wherein X-Y is -NHSO2- or -SO2NH-; R1 is H, CN or alkyl; R2 is selected from COOH and a tetrazolyl group; R3 is selected from H, Cl and alkyl; R4 is selected from H and halo; R5 is selected from H, alkyl, haloalkyl, SO2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R6 is H; R7 is selected from H, CN, haloalkyl, halo, SO2-alkyl, optionally substituted heteroaryl, SO2NR14R15, CONR10R11 and alkyl; R8 is selected from H, alkyl, haloalkyl and halo; R9 is H or halo; and R10, R11, R12, R14, and R15 are H or alkyl; R13 is selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; and m is 0-3. The compounds of formula (I) modulate ERAP1 (endoplasmic reticulum aminopeptidase 1) and are for use in treating proliferative, immune or inflammatory disorders, particularly cancer or leukemia. The compounds of formula (I) stimulate a neo-antigen directed immune response in the subject. A method for producing an antigen-presenting cell which presents a neo-antigen using compounds of formula (I) is disclosed. An immunogenic composition comprising an antigen-presenting cell is also disclosed. Exemplified compounds include 4-cyclopropyl-3-(N-(2-(morpholin-3-yl)-5-(trifluoromethyl)phenyl)sulfamoyl)benzoic acid.

Provided is an antibody-drug conjugate for use in the treatment of cancer in which one or more KRAS mutants, particularly a KRAS G12V mutant, a KRAS G12D mutant, and a KRAS G12C mutant, are expressed. Also provided are a drug and a drug-linker conjugate for use in the antibody-drug conjugate.　The present inventors have produced an antibody-drug conjugate with which a heterocyclic compound represented by formula (II) and having an activity of inducing the decomposition of KRAS mutant proteins can be delivered to cancer in which EGFRs are expressed, the production being achieved by linking the compound to an anti-EGFR antibody. The present inventors have also discovered a drug-linker conjugate for use in the antibody-drug conjugate or a salt thereof. In cancer in which EGFRs are expressed, the antibody-drug conjugate induces the decomposition of one or more KRAS mutants, particularly a KRAS G12V mutant protein, a KRAS G12D mutant protein, and a KRAS G12C mutant protein, thereby inhibiting the KRAS mutants and exhibiting an anti-tumor effect.

The invention discloses a method for comprehensively identifying PFAS in an environment by combining targeted analysis, suspicious screening and non-targeted identification. The method comprises the following steps: S1, carrying out liquid chromatography-high resolution mass spectrometry fullscan / DDA / DIA analysis on an environmental sample; s2, carrying out liquid chromatography-high resolution mass spectrometry analysis on the plurality of PFAS standard substances; s3, according to a public chemical database and literature, collecting names and molecular formulas of a plurality of PFASs, calculating an accurate mass number, and jointly establishing a suspicious screening database in combination with an open-source MS2 spectrogram library; s4, establishing a non-targeted identification work flow by combining the mass number characteristics of the PFAS, the characteristic MS2 fragments, the characteristic neutral loss and the homolog characteristics; and S5, integrating the targeted analysis compound, the candidate compound subjected to suspicious screening and the candidate compound subjected to non-targeted identification, and comprehensively identifying the PFAS in the environmental sample. According to the method disclosed by the invention, the known and unknown perfluoroalkyl / polyfluoroalkyl compounds are fully identified through three complementary analysis technologies.

The invention relates to the technical field of drug research and development, and discloses a drug-like molecule screening system and method based on deep learning, and the system comprises a physical and chemical characteristic analysis module which is used for calculating molecular descriptors of compounds and generating a visual characteristic distribution chart; and the drug-like molecule screening module integrates a Lipinski rule, a Veber rule, a Ghose rule and a Muegge rule, and supports a user to customize a screening rule. Compound characteristics are comprehensively analyzed through the physical and chemical characteristic analysis module, flexible screening is achieved through the drug-like molecule screening module, toxicity risks are accurately recognized through the toxicity assessment module, the affinity assessment module is combined to assess the binding capacity in multiple ways, and the synthesis feasibility assessment module plans an efficient and low-cost synthesis path. The dynamic feedback optimization module continuously improves the system performance; all the modules work cooperatively, the problems of scattered tools, insufficient precision, low planning efficiency, optimization deficiency and the like in the prior art are effectively solved, the medicine research and development efficiency is greatly improved, and the research and development risk and cost are reduced.

A computer implemented method may collect a set of known drug compounds from a database, and create augmented datasets with labeled and unlabeled chemical data and biological data. A computer implemented method may train a neural network using the expanded training set to generate a prediction score of bioactivity of candidate drug compounds towards the biological target, wherein the contribution of the second plurality of unlabeled samples in training the neural network is scaled by a parameter. A computer implemented method may output one or more refined neural network models capable of generating candidate drug compounds with predicted activity. A computer implemented method may generate a candidate drug compound by inputting a candidate drug compound with chemical data into the trained neural network model.

Disclosed herein are compounds useful for the inhibition of KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R or G12C. The compounds have a general Formula (I): (I) or pharmaceutically acceptable salts thereof, wherein the variables of Formula (I) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R or G12C disorder.

Compounds disclosed herein or their pharmaceutically acceptable salts can modulate the G12D mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds disclosed herein or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

The invention relates to the technical field of nano delivery carriers, in particular to an ionizable lipid compound with a three-dimensional space structure and a preparation method and application thereof. The ionizable lipid compound provided by the invention comprises a three-dimensional space structure constructed by a polar head group, a connecting bond and a hydrophobic tail. Diversified ionizable lipid compounds with different three-dimensional space structures are constructed by changing various polar head groups, connecting bonds and hydrophobic tails contained in an ionizable lipid compound combinatorial library, and the ionizable lipid compounds have excellent mRNA (messenger ribonucleic acid) binding capacity. The invention also provides preparation and application of the ionizable lipid compound with the advantageous three-dimensional space structure. The novel ionizable lipid compound with an advantageous three-dimensional space structure has stronger binding capacity with mRNA, and lipid nanoparticles synthesized from the novel ionizable lipid compound have excellent physicochemical characteristics, high cell uptake rate, lysosome escape rate and cell and in-vivo transfection rate, and have the function of specifically targeting liver, spleen or lung.

Compounds are provided having the following structure:or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1a, R1b, R2a, R2b, R3a, R3b, R4a, R4b, R5, R6, R7, R8, R9, L1, L2, a, b, c, d and e are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.

The invention relates to a furan ring-containing compound as well as a pharmaceutical composition and application thereof. Specifically disclosed is a compound represented by formula I or a pharmaceutically acceptable salt thereof. The compound provided by the invention has one or more of the following advantages: (1) the structure is novel; (2) the compound has a good retarding effect (inhibiting effect) on the activity of a Nav1.8 channel; and (3) the compound has good selectivity to other subtypes of Nav and is high in safety. # imgabs0 #

The invention discloses a carbonyl reductase, a mutant and an application of the carbonyl reductase in synthesis of a chiral alcohol compound. The carbonyl reductase mutant is obtained by performing single-site or multi-site mutation on the 96th site, the 145th site, the 202nd site or the 206th site of the amino acid sequence of the carbonyl reductase LbCR derived from lactobacillus brevis as shown in SEQ ID No.2. The activity and stability of the carbonyl reductase LbCR mutant are obviously improved, and the carbonyl reductase LbCR mutant has a wide substrate spectrum. Compared with a wild type, the mutant LbCRM4 has the advantages that the enzyme activity is improved by 86.3 times, the substrate conversion rate is greater than 99%, the e.e.p value of the product is always kept at 99.5% or above, the space time yield reaches 1288.9 g / L / d, and the half-life period at 40 DEG C is 101.4 h and is improved by 83.5 times. The LbCR mutant has an industrial application prospect.

The invention discloses a compound represented by a formula (1), or a tautomer, a mesomer, a raceme, an enantiomer, a diastereoisomer, or a mixture form thereof, or a pharmaceutically acceptable salt, a prodrug or a solvate thereof, the structure of the formula (1) is represented as follows: # imgabs0. Strong hydrophilic sulfonic acid inner salt and / or phosphoric acid inner salt side chains are introduced at the position of (AAA and the like)-PAB (self-destruction group), so that the druggability (including hydrophilicity and stability) of the antibody drug conjugate corresponding to the compound is greatly enhanced, the in-vivo drug removal effect is reduced, and the tumor treatment effect is improved.

Compounds useful as biologically active compounds are disclosed. The compounds have the following structure (I): or a stereoisomer, tautomer or salt thereof, wherein R1, R2, R3, R4, R5, L, L1, L2, L3, L4, M, q, w and n are as defined herein. Methods associated with preparation and use of such compounds is also provided.

The invention discloses a multistage crosslinking organic boron crosslinking agent capable of resisting high temperature of 180 DEG C and a preparation method of the multistage crosslinking organic boron crosslinking agent. The crosslinking agent comprises the following components in parts by weight: 3-4 parts of a boron-containing polymeric monomer, 10-12 parts of boric acid ester, 2-3 parts of a boron-containing compound, 15-18 parts of a solvent 1, 2-3 parts of a solvent 2, 0.5-1 part of a first ligand, 13-15 parts of a second ligand, 20-25 parts of a third ligand, 1-1.5 parts of alkenyl oxygen-containing silane and 2-3 parts of a strong hydrophilic monomer. The preparation method comprises the following steps: firstly, carrying out surface graft copolymerization on a boron-containing polymeric monomer to the surface of a nano material to prepare a boron-containing small-molecule polymer, and then chelating the boron-containing small-molecule polymer, boric acid ester, a boron-containing compound and the like step by step by using various chelating agents to obtain the organic boron cross-linking agent disclosed by the invention. After the cross-linking agent is compounded with a fracturing fluid, boron carriers with different release speeds are opened layer by layer, borate ions are released to be subjected to multi-stage cross-linking with the fracturing fluid, slow gelling is realized, a unique nano material is introduced to enhance the spatial structure and mechanical stability of gel, and the temperature resistance of the fracturing fluid is greatly improved.

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.