145 results about "IRAK4" patented technology

The present disclosure relates generally to various salt forms and compositions thereof useful for the modulation of interleukin-1 receptor-associated kinase 4 ("IRAK4") via ubiquitination and / or degradation and uses of the same in the treatment various diseases.

The present invention relates to the technical field of chemical pharmacy, and in particular to a compound for degradation of a targeted interleukin-1 receptor-associated kinase 4 (IRAK4), and a pharmaceutically acceptable salt of the compound. The compound can be used for treating or preventing IRAK4-mediated immune diseases, inflammatory diseases, and cancers.

Disclosed are compounds of Formula (I) or a salt or prodrug thereof, wherein: X1 and X2 are independently C or N, provided that zero or one of X1 and X2 is N; Ring A represented by the structure is: or; and Q, R1, R2, R3, R4, R6, and p 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.

A nanoparticle for delivering an interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor to a subject and methods for treating inflamed tissue in a subject using the nanoparticle.

Disclosed in the present invention are a five-membered ring-fused six-membered ring compound, a preparation method therefor, and a pharmaceutical composition and the use thereof. Provided in the present invention is a compound as represented by formula (I), or a pharmaceutically acceptable salt or an isotope compound thereof. The compound of the present invention has an inhibition and / or degradation effect on IRAK4.

Disclosed in the present invention are a five-membered ring-fused six-membered compound, a preparation method therefor, and a pharmaceutical composition and the use thereof. Provided in the present invention is a compound as represented by formula (I), or a pharmaceutically acceptable salt or an isotope compound thereof. The compound of the present invention has an inhibition and / or degradation effect on IRAK4.

A five-membered-fused six-membered compound, a preparation method, a pharmaceutical composition, and the use. The penta-fused hexa-heterocyclic compound is a compound represented by formula (II) or (III). The compound has an inhibition or / and degradation effect on IRAK4.

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 invention relates to an IRAK4 degradation agent and application thereof, in particular to a bifunctional compound shown in the following formula (I), an isomer, a deuterated substance or pharmaceutically acceptable salt of the bifunctional compound, and application of the compound in treating IRAK4-mediated related diseases. # imgabs0 #

Disclosed are compounds of Formula (I) or a salt or prodrug thereof, wherein R1, R2, and R3 are defined 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 discloses a compound synthesized based on a PROTAC technology and a synthesis method and application thereof.The compound is shown in the formula I. IRAK4 serves as a core of a MyD88 dependent signal channel, is an effective target for inhibiting a TLR / IL-R signal channel, can be used for treating various skin diseases including atopic dermatitis (AD) and has potential patent medicine prospects. # imgabs0 #

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

Provided herein are methods of enhancing gene therapy in an individual by administering an IRAK modulator (e.g., an IRAK-4 degrading agent) with a gene therapy to inhibit innate immunity to the gene therapy. In some embodiments, the gene therapy uses an adeno-associated virus (AAV) vector, an adenoviral vector, a lentiviral vector, a herpes simplex virus (HSV) vector, or lipid nanoparticles. Also provided herein are methods for selecting an individual for treatment with an IRAK modulator in combination with a gene therapeutic agent.

The invention provides a preparation method of an IRAK4 targeted protein degradation agent key intermediate, and belongs to the field of drug synthesis. According to the invention, 2-pyrrolidone and a benzimidazolone compound are used as raw materials to prepare a key intermediate of the IRAK4 targeted protein degradation agent, a protecting group is introduced to 2-pyrrolidone, and a reaction route is optimized, so that generation of a by-product 3-bromo-1-(3-methyl-2-oxo-2, 3-dihydro-1H-benzo [D] imidazole-4-yl) piperidine-2, 6-diketone is avoided, and the yield of the IRAK4 targeted protein degradation agent is improved. The product yield is obviously improved, the product is easier to purify, and the method has a wide application prospect and is convenient for industrialization.

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 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 disclosure relates generally to various salt forms and compositions thereof useful for modulating interleukin-1 receptor associated kinase 4 ("IRAK4") via ubiquitination and / or degradation and their use in the treatment of various 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.

Relates to a compound for inhibiting IRAK4 activity and application thereof, and particularly provides a compound as shown in a formula A, or enantiomers, diastereoisomers, racemate, tautomers, stereoisomers, geometric isomers, nitrogen oxides, metabolites or pharmaceutically acceptable salts, esters, solvates, hydrates, isotope labeled compounds (preferably deuterated compounds) or prodrugs of the compounds. # imgabs0 #

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,

An aromatic compound containing an E3 ligand fragment, a pharmaceutical composition containing the same, and uses thereof. An aromatic compound, enantiomer, diastereomer, racemate, and mixture thereof as shown in Formula E, or a pharmaceutically acceptable salt thereof. Such compounds containing E3 ligand fragments can be used to prepare PROTAC compounds, which can recruit target proteins to CRBN E3 ubiquitin ligases and degrade them or inhibit the activity of target proteins in other ways. A degrader of the enzyme IRAK4 containing the same can effectively degrade IRAK4 or inhibit the activity of IRAK4 in other ways. It has very good application prospects in IRAK4-mediated diseases including immune diseases, tumors, Alzheimer's disease, and fibrotic diseases, and provides a new option for clinical screening and / or preparation of drugs for diseases related to IRAK4 activity.

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.

The present disclosure relates to compounds and methods for degrading interleukin receptor-associated kinase 4 (IRAK4), the methods comprising administering to the subject a compound of Formula (I). In some embodiments, the disclosure provides compounds and methods for treating cancer.