76 results about "IRAK4" patented technology

Disclosed are compounds of Formula (I) or a salt or prodrug thereof, wherein: X is C or N; Y is C or N; Z is CR4 or N; provided that when: (i) X is N, then Y is C; and (ii) X is C, then Y is N and Z is N; and wherein R1, R2, R3, and R4 are define herein. Also disclosed are methods of using such compounds as modulators of IRAK4, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing inflammatory and autoimmune diseases, or in the treatment of cancer.

The invention provides a polysubstituted aromatic amine compound (as shown in a general formula I) as well as a preparation method, a pharmaceutical composition and application thereof, and particularly provides a compound with a structure as shown in the general formula I as well as an optical isomer, a medicinal salt or a mixture of the compound and the optical isomer. The compound has good IRAK4 inhibitory activity, so that the compound can be used for treating, preventing and relieving IRAK4 target related diseases, especially for treating autoimmune diseases such as arthritis, inflammatory bowel disease and the like, malignant tumors such as leukemia and the like or other related diseases.

The present disclosure provides bifunctional compounds as IRAK4 degraders via ubiquitin proteasome pathway, and method for treating diseases modulated by IRAK4.

Disclosed in the present invention are polymorphs of an IRAK-4 degrading agent. Specifically, the present invention provides a plurality of crystal forms of an IRAK-4 degrading agent represented by the following formula (I), salts thereof and crystal forms thereof, as well as a pharmaceutical composition thereof, the preparation therefor and the use thereof. The crystal forms provided by the present invention can be used for preparing drugs for treating and / or preventing IRAK4-mediated related diseases.

The present application provides a protein degradation targeting chimera molecule and application thereof, the protein degradation targeting chimera molecule has the structure shown in formula (I), the protein degradation targeting chimera molecule of the present application can significantly degrade IRAK kinase, which shows efficient, high selective IRAK4 and / or IRAK1 degradation effect, and can be used for treating or preventing diseases related to IRAK4 and / or IRAK1 activity.

The application discloses a compound for targeting IRAK4 protein degradation and application thereof. The compound is a compound shown in formula I, and formula I is T-L-E. In formula I, T is selected from groups shown in formulae T-1 and T-2; E is selected from groups shown in formulae E-1, E-2 and E-3; and L is a linking group with a length of 0-15 atoms. The compound adopts a double-target molecule structure, wherein one end of the molecule is targeted to combine with E3 ligase, and the other end of the molecule is targeted to combine with a target protein (IRAK4 protein) to be degraded. The two ends of the structure are connected through a chain (linker) to form a complete compound molecule. The molecule can reduce the IRAK4 protein level, so that the kinase catalytic function and the scaffold function of the IRAK4 protein are lost at the same time, and a new direction is provided for the treatment of IRAK4 related diseases.

Provided are a crystal form of a five-membered and six-membered compound, a preparation method and application thereof, in particular, a crystal form A, a crystal form B, a crystal form C, a crystal form D, a crystal form F, a crystal form G, a crystal form H, a crystal form I or a crystal form J of a five-membered and six-membered compound as shown in formula X. The crystal form A has an X-ray powder diffraction pattern expressed by a 2θ angle using Cu-Kα radiation, and has diffraction peaks at 6.9±0.2°, 11.2±0.2°, 12.2±0.2°, 13.7±0.2°, 17.3±0.2°, 18.2±0.2° and 24.3±0.2°. The crystal form of the five-membered and six-membered compound provided has an inhibitory or / and degrading effect on IRAK4, has potential clinical application value, is expected to improve the prognosis of patients and reduce the possibility of drug resistance, and has good solubility, physical and chemical stability and mechanical stability.

The present application relates to a compound for inhibiting IRAK4 activity and a use thereof, and specifically provides a compound as represented by formula A, 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 (preferably a deuterated substance), or a prodrug thereof,

The present specification relates to novel physical forms of a indazole-5-carboxamide derivative, as well as solvate and salt forms of the same compound. A process for the preparation of the compound and uses of the new physical forms are also provided.

Disclosed are compounds of Formula (I) or a salt or prodrug thereof, wherein: X is CR4a or N; Y is CR4b or N; Z is CR4d or N; provided that zero or 1 of X, Y, and Z is N; and R1, R2, R3, R4a, R4b, R4c, and R4d are define herein. Also disclosed are methods of using such compounds as modulators of IRAK4, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing inflammatory and autoimmune diseases, or in the treatment of cancer.

The present invention relates to compounds and compositions for the treatment of hematological disorders. The present invention provides methods for the treatment of hematological disorders, such as acute myeloid leukemia, using substituted heterocyclic compounds and pharmaceutically acceptable salts thereof. The compounds inhibit IRAK4 and FLT-3 kinases.

The present application relates to a novel IRAK4 inhibitor of formula (I) and a compound for inhibiting and degrading IRAK4 protein, a preparation method therefor and use thereof, and also relates to a pharmaceutical composition comprising the IRAK4 inhibitor or the compound for inhibiting and degrading IRAK4 protein.

The invention relates to an interleukin-1 receptor-associated kinase 4 (IRAK4) degradation agent and application of the IRAK4 degradation agent in preparation of a medicine for treating IRAK4-associated diseases. The invention specifically relates to a compound as shown in a formula (I), and isomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof.

This invention provides a method for preparing a key intermediate of an IRAK4-targeting protein degrader, belonging to the field of pharmaceutical synthesis. This invention uses 2-pyrrolidone and benzimidazolone compounds as raw materials to prepare the key intermediate of an IRAK4-targeting protein degrader. By introducing a protecting group onto 2-pyrrolidone and optimizing the reaction route, the generation of the byproduct 3-bromo-1-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[D]imidazol-4-yl)piperidine-2,6-dione is avoided, significantly improving the product yield, making the product easier to purify, and possessing broad application prospects and facilitating industrialization.

The present disclosure relates to IRAK4 degradation agent compounds, and specifically provides compounds of formula (I) or pharmaceutically acceptable salts thereof, the compounds having substituents and structural characteristics described herein. Also described are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and the use of said compound or a pharmaceutically acceptable salt thereof in medicine.

The present invention provides bicyclic heterocyclyl kinase enzyme inhibitor compounds of formula (I), which are therapeutically useful as kinase inhibitors, particularly IRAK4 inhibitors.wherein A, Y, Z, X1, X2, X3, R1, R3, ‘m’, ‘n’ and ‘p’ have the meanings given in the specification and pharmaceutically acceptable salts or stereoisomers thereof that are useful in the treatment and prevention of diseases or disorders, in particular their use in diseases or disorders mediated by kinase enzyme, particularly IRAK4 enzyme. The present invention also provides pharmaceutical compositions comprising at least one of the compounds of compound of formula (I) together with a pharmaceutically acceptable carrier, diluent or excipient therefor.

Disclosed herein are novel bifunctional compounds formed by conjugating an IRAK4 inhibitor moiety to an E3 ligase ligand moiety, which function to recruit targeted proteins to E3 ubiquitin ligases for degradation; as well as methods of making and uses thereof.

The present application relates to compounds of formula (A), wherein R1 is selected from formula (II) and formula (III) and R2 is selected from formula (IV), formula (V) and formula (VI), as IRAK4 inhibitors for use in methods of treating, for example, asthma and chronic obstructive pulmonary disease (COPD), cancer, inflammatory diseases and autoinflammatory / autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, myositis, Sjogren's syndrome, systemic sclerosis, gout, endometriosis, atopic dermatitis and psoriasis. Preferred compounds of the present application are, for example: N-(imidazo[l,2-b]pyridazin-3-yl)-l-cyclohexyl-2H-indazole-5-carboxamide, N-(pyrazolo[l,5-a]pyrimidin-3-yl)-l-cyclohexyl-2H-indazole-5-carboxamide, N-(imidazo[l,2-b]pyridazin-3-yl)-l-azaspiro[4.5]dec-8-yl-2H-indazole-5-carboxamide and N-(pyrazolo[l,5-a]pyrimidin-3-yl)-l-azaspiro[4.5]dec-8-yl-2H-indazole-5-carboxamide derivatives. An exemplary compound of the present application is, for example: N-(imidazo[l,2-b]pyridazin-3-yl)-6-methoxy-2-((5r,8r)-l-methyl-2-oxo-l-azaspiro[4.5]dec-8-yl)-2H-indazole-5-carboxamide (Example 1): formula (VII).

This application relates to a proteolytic targeting chimeric compound that degrades IRAK4 of formula (A), a method for producing the same, a pharmaceutical composition containing the compound, and uses of the pharmaceutical composition to treat diseases, disorders, or conditions related to IRAK4 protein kinase. [Case 1] JPEG2026528824000527.jpg28106

The present application relates to an IRAK4-degrading protein degradation targeting chimera compound of formula (A) and a preparation method thereof, a pharmaceutical composition comprising the compound, and use of the pharmaceutical composition in treatment of diseases, disorders or conditions associated with IRAK4 protein kinase.

An IRAK4 degradation agent as represented by structural formula PTM-L-ULM (I), and a preparation method therefor and the use thereof. The provided compound can effectively inhibit and / or degrade IRAK4 kinase protein in a cell and inhibit an immune cell from producing IL-6.

The present invention provides methods of treating hematological disorders such as acute myeloid leukemia, using substituted heterocyclic compounds and pharmaceutically acceptable salts thereof. The compounds inhibit the kinases IRAK4 and FLT-3.

The present disclosure provides a method of treating an inflammatory disease / disorder, acute myeloid leukemia (AML), or myelodysplastic syndrome (MDS) in a subject comprising administering to the subject a compound that inhibits IRAK1 and IRAK4. The present disclosure further provides a method of determining a compound that is effective at treating an inflammatory disease / disorder, AML, or MDS.

The present disclosure relates generally to processes for preparing compounds that are inhibitors of kinase IRAK4 and synthetic intermediates prepared thereby.

Provided are a class of multi-targeted inhibitors of IRAK4 and BTK, and the use thereof in preparing a drug for treating IRAK4- and BTK-related diseases. The present invention specifically relates to the compounds represented by formula (II), isomers thereof or pharmaceutically acceptable salts thereof.

Disclosed herein are novel bifunctional compounds formed by conjugating an IRAK4 inhibitor moiety to an E3 ligase ligand moiety, the function of these bifunctional compounds being to recruit a target protein to an E3 ubiquitin ligase for degradation, as well as methods of making and uses thereof.