9842 results about "Stereochemistry" patented technology

A PARP1 inhibitor compound has a structure of: Formula (I), R1 and R4 are independently selected from H and an organic group. R2 and R3 are independently absent, H, or an organic group. Z1 and Z2 are independently C or N. L has the structure: Formula (II). Each X1 is independently selected from C and N. Each X2 is independently selected from C, N, O and S. n, m, p, q, r and s are each in the range 0 to 6. m+n, p+q, and r+s are each in the range 2 to 6. Each R5A, R5B, R5C, and R6 is independently absent, H, or an organic group. Qa, Qb, Qc are each independently a bond or an organic linker. The compounds are for use in medicine, e.g. for use in treating cancer. Also provided are compositions and kits comprising the compounds, and methods of synthesising the compounds.

A compound as represented by formula I-1, a stereoisomer or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing same, and the use thereof as a PARP-1 inhibitor in the preparation of a drug for treating related diseases. Each group in formula I-1 is as defined in the description.

The present invention discloses substituted 2-amino-9-(3,3-difluoropiperidin-4-yl)-7,9-dihydro-8H-purin-8-one compounds compounds having the structural formula represented by formula (I)： The substituted 2-amino-9-(3,3-difluoropiperidin-4-yl)-7,9-dihydro-8H-purin-8-one compounds, derivatives and pharmaceutically acceptable salts thereof of the present invention are capable of acting as a drug characteristic of a protein kinase inhibitor, in particular for the expression of a protein through a DNA-dependent protein kinase (DNA-PK) and can be used to treat or prevent disorders associated with abnormal protein kinase activity, such as cancer, cancer with brain metastases, cancer with meningeal metastases, glioma, glioblastoma, DIPG, and the like either as monotherapy or combination with other treatments, such as radiation therapy or chemotherapy.

Disclosed in the present invention is a novel fused heterocyclic compound having CDK target inhibitory activity. Specifically disclosed are a compound having a structure as shown in formula (I) and serving as a CDK target inhibitor, or a pharmaceutically acceptable salt, solvate, hydrate, isotopic substituent or isomer thereof.

The invention relates to a disubstituted nitrogenous five-membered heteroaryl compound serving as a kinase inhibitor and application of the disubstituted nitrogenous five-membered heteroaryl compound. The chemical structure of the disubstituted nitrogenous five-membered heteroaryl compound disclosed by the invention is shown as a formula A, the compounds of the invention are CHK1 inhibitors. Therefore, the compounds of the present invention can be used for the treatment of cancer. # imgabs0 #

The invention relates to an inhibitor containing cyclopentane derivatives as well as a preparation method and application of the inhibitor. Particularly, the invention relates to a compound shown in a general formula (I), a preparation method of the compound, a pharmaceutical composition containing the compound and application of the compound as an inhibitor in treatment of cardiovascular diseases, cerebrovascular diseases and other diseases, and substituents in the general formula (I) are as defined in the specification. # imgabs0 #

The invention relates to compounds of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof that selectively inhibit the activity of K-Ras G12D protein, compositions comprising the same, the methods of using the same and related intermediates.

A CHRM4 receptor agonist and the use thereof. Disclosed in the present invention are a compound as represented by formula (I), or a stereoisomer, a deuterated substance, a solvate, an eutectic or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition thereof, and the use thereof in the preparation of a drug for treating / preventing CHRM4-mediated diseases, wherein each group in formula (I) is as defined in the description.

The present invention relates to a bifunctional Kras modulator (K-T or K-L-T) and the use thereof, wherein K represents a targeting group and is a modulator of a Kras protein (target protein), T is a ligand group of an E3 ubiquitin ligase, and L is a divalent linking group that chemically links the targeting group (K) to the ligand group (T). The bifunctional modulator or compound and a composition thereof disclosed in the present invention have pharmacological activity of degrading or inhibiting the target protein, and can be used for treating, inhibiting or preventing Kras-related diseases or disorders.

The present invention relates to a new crystal form of Resmetirom and a preparation method therefor, a pharmaceutical composition containing the crystal form, and a use of the crystal form in preparation of a THR-β selective agonist pharmaceutical formulation and a pharmaceutical formulation for treating MASH and HeFH.

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.

Disclosed in the present invention is a new substituted heterocyclic compound having GSPT1 degradation activity, and particularly disclosed is a compound having the structure as shown in formula (I) as a GSPT1 degradation agent, or a pharmaceutically acceptable salt, a solvate, a hydrate, an isotope substitute or an isomer thereof. The compound can be used for preventing or treating diseases related to GSPTs / MYC targets or signaling pathways.

The present disclosure relates generally to GLP-1 agonists and pharmaceutical compositions comprising the same, as well as methods for treating a GLP-1 associated disease, disorder, or condition.

Provided are diaminocyclopentyl substituted heteroaryl derivatives, the use thereof and a preparation method therefor. In particular, the present disclosure relates to compounds represented by formula (I)each substituent of which is defined in the description, and a preparation method therefor. The compounds can be used as PCSK9 inhibitors to prevent and / or treat PCSK9-mediated diseases and disorders.

A novel prodrug compound having GLP1R agonist activity. Specifically disclosed is a compound having a structure represented by formula (I) as a GLP1R agonist, or a pharmaceutically acceptable salt, solvate, hydrate, isotopic substituent or isomer thereof.

To provide a compound which is a novel proline derivative, and to provide a pharmaceutical composition comprising the compound for the treatment of, for example, systemic sclerosis (SSc) and non-alcoholic steatohepatitis (NASH).SOLUTION: A pharmaceutical composition comprises, as a cGAS inhibitor, a compound which is a novel proline derivative encompassed by formula (I), or a prodrug, a pharmaceutically acceptable salt, or a stereoisomer of the compound.SELECTED DRAWING: None

The invention belongs to the field of medical chemistry, relates to a compound serving as a WRN inhibitor and application of the compound, and particularly provides a compound shown in a formula (I) or pharmaceutically acceptable salt, isomer, solvate, crystal or prodrug of the compound, processes for their preparation, pharmaceutical compositions containing these compounds and the use of these compounds or compositions for the treatment of diseases associated with WRN. # imgabs0 #

The invention discloses an acyltransferase mutant and application of the acyltransferase mutant in synthesis of N-acetyl-trans-4-hydroxyproline, and belongs to the technical field of enzyme engineering. The acyltransferase mutant provided by the invention contains 10th and 95th mutations on the basis of a corresponding amino acid sequence, such as a sequence as shown in SEQ ID NO.1, or contains 62nd or 64th mutations while containing the 10th and 95th mutations. Compared with an original enzyme before mutation, the acyltransferase mutant obtained by the invention has higher acyltransferase activity, and the conversion rate of trans-4-hydroxy-L-proline is greatly improved, so that the yield of N-acetyl-trans-4-hydroxy proline is further improved, and the yield of N-acetyl-trans-4-hydroxy proline is improved. After the surfactant and the metal ions are added, the yield of the N-acetyl-trans-4-hydroxyproline synthesized by the mutant D62K / D10V / D95I under the catalysis is up to 18.7 g / L.

The present application relates to a GLP-1 receptor agonist, which is a compound of formula (II) or a pharmaceutically acceptable salt thereof, and a method for treating or preventing a GLP-1 receptor-mediated disease or disorder or regulating a GLP-1 receptor.

The invention discloses a glycosyl transferase UGTSL2 mutant. The UGTSL2 mutant is subjected to any one or more of the following mutations on the basis of an amino acid sequence as shown in SEQ ID NO.1: the 23rd amino acid is mutated from N to E; the 41st amino acid is mutated from R to P; the 91st amino acid is mutated from H to K; the 95th amino acid is mutated from K to D; the 123 amino acid is mutated from E to P; the 136th amino acid is mutated from L to F; the 151st amino acid is mutated from R to F; the 124 amino acid is mutated from H to E; the 168th amino acid is mutated from V to Y; the 198 amino acid is mutated from C to K; the 202nd amino acid is mutated from T to E; the 217th amino acid is mutated from W to K; the 225th amino acid is mutated from P to L; the 226 amino acid is mutated from F to V; the 285th amino acid is mutated from A to V; and the 333rd amino acid is mutated from I to V and the like.

The present disclosure provides crystalline forms, solvates and hydrates of (R)-5-fluoro-2-methyl-1-((R)-5-(pyridin-2-yl)-2,3-dihy dro-lH-indene-2-carbonyl)indoline-6- sulfonamide, and methods of making.

The invention relates to the technical field of preparation methods of polypeptide drugs, and provides a solid-phase preparation method of tirpotide, which comprises the following steps: by taking amino resin as initial resin, sequentially coupling amino acid and small-fragment peptide according to an amino acid sequence of the tirpotide by using a solid-phase synthesis method to synthesize tirpotide resin; and cracking and purifying the tilpotide resin to obtain a pure tilpotide product. Wherein the small fragment peptide is 1-4 tetrapeptide fragment Boc-Tyr (tBu)-Aib-Glu (OtBu)-G1y-OH, 5-6 dipeptide fragment Fmoc-Thr (tBu)-Phe-OH, 7-8 dipeptide fragment Fmoc-Thr (tBu)-Ser (tBu)-OH, 10-11 dipeptide fragment Fmoc-Tyr (tBu)-Ser (tBu)-OH, 12-13 dipeptide fragment Fmoc-Ile-Aib-OH, 17-18 dipeptide fragment Fmoc-Lys (AEEA-AEA-gamma-Glu (alpha-OtBu)-Ecosanoic acid (mon-tBu), 20 side chain peptide Fmoc The coupling agent coupling the amino acid and the small fragment peptide is selected from the group consisting of Oxyma and DIC, TPTU and TMP or COMU and DIEA. The crude product of the tirpotide prepared by the method disclosed by the invention is high in yield and high in purity.