Polycyclic derivative inhibitor as well as preparation method and application thereof
What is Al technical title?
Al technical title is built by PatSnap Al team. It summarizes the technical point description of the patent document.
A technology of heterocyclic group and cycloalkyl group is applied in the field of polycyclic derivative inhibitors and their preparation, which can solve the problem of low selectivity and the like
Active Publication Date: 2020-08-04
SHANGHAI HANSOH BIOMEDICAL +1
View PDF8 Cites 22 Cited by
Summary
Abstract
Description
Claims
Application Information
AI Technical Summary
This helps you quickly interpret patents by identifying the three key elements:
Problems solved by technology
Method used
Benefits of technology
Problems solved by technology
At present, there is no TYK2 selective inhibitor on the market. Early JAK inhibitors mainly ...
Method used
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more
Image
Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
Click on the blue label to locate the original text in one second.
Reading with bidirectional positioning of images and text.
Smart Image
Examples
Experimental program
Comparison scheme
Effect test
Embodiment 1
[0188] 6-(cyclopropylcarboxamide)-4-((4-methoxy-5-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino) -N-(methyl-d 3 ) Preparation of pyridazine-3-carboxamide
[0189]
[0190] Step 1: Preparation of 4-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine
[0191]
[0192] 5-Bromo-4-methoxypyridin-3-amine (2.02g, 10mmol), bis-pinacolyldiborane (3.05g, 12mmol), [1,1'-bis(diphenylphosphine) Ferrocene] palladium dichloride dichloromethane complex (816.6mg, 1mmol), potassium acetate (2.45g, 25mmol), mixed in dioxane (20mL), the reaction system nitrogen replacement three times, 100 ° C reaction overnight, cooled to room temperature, concentrated the reaction solution under reduced pressure, and the residue was water and CH 2 Cl 2 Separation, the organic phase was separated and washed with saturated aqueous sodium chloride, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure and then column chromatographed to obta...
Embodiment 2
[0215] 6-(cyclopropylcarboxamide)-4-((3-methoxy-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-4-yl)amino) -N-(methyl-d 3 ) Preparation of pyridazine-3-carboxamide
[0216]
[0217] 6-(cyclopropylcarboxamide)-4-((3-methoxy-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-4-yl)amino) -N-(methyl-d 3 ) The preparation of pyridazine-3-carboxamide refers to Example 1.
[0218] MS m / z(ESI):427.2[M+H] + .
Embodiment 3
[0220] 6-(cyclopropylcarboxamide)-4-((3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino) -N-(methyl-d 3 ) Preparation of pyridazine-3-carboxamide
[0221]
[0222] 6-(cyclopropylcarboxamide)-4-((3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino) -N-(methyl-d 3 ) The preparation of pyridazine-3-carboxamide refers to Example 1.
[0223] MS m / z(ESI):427.2[M+H] + .
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more
PUM
Login to view more
Abstract
The invention relates to a polycyclic derivative inhibitor as well as a preparation method and application thereof. Particularly, the invention relates to a compound represented by a general formula,the preparation method of the compound, a pharmaceutical composition containing the compound and the application of the compound as an intracellular non-receptor tyrosine kinase to mediation of signaltransduction and activation of various cell factors. The compound plays a key role in the biological process of participating in immunoregulation, immune cell proliferation and the like, is closely related to various inflammatory diseases such as rheumatoid arthritis, dermatitis, psoriasis, inflammatory bowel diseases (ulcerative colitis and Crohn's disease) and the like, and has the same substituent groups in the following general formula (I) as defined in the specification.
Description
technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a polycyclic derivative inhibitor and its preparation method and application. Background technique [0002] Janus kinase (JAK) is an intracellular non-receptor tyrosine kinase that mediates the signaling and activation of various cytokines. The JAK kinase family is divided into four subtypes, JAK1, JAK2, JAK3, and TYK2, each of which mediates different types of cytokine signaling pathways, and JAK-1, JAK-2, and TYK-2 are found in various human tissue cells Expression, JAK-3 is mainly expressed in various hematopoietic tissue cells. The common feature of cytokine receptors is that the receptor itself does not have kinase activity, but the intracellular segment of the receptor has a binding site for the tyrosine kinase JAK. When the cytokine receptor binds to its ligand, the receptor-coupled JAKs are activated, and the receptor is phosphorylated, and the phosphorylated t...
Claims
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more
Application Information
Patent Timeline
Application Date:The date an application was filed.
Publication Date:The date a patent or application was officially published.
First Publication Date:The earliest publication date of a patent with the same application number.
Issue Date:Publication date of the patent grant document.
PCT Entry Date:The Entry date of PCT National Phase.
Estimated Expiry Date:The statutory expiry date of a patent right according to the Patent Law, and it is the longest term of protection that the patent right can achieve without the termination of the patent right due to other reasons(Term extension factor has been taken into account ).
Invalid Date:Actual expiry date is based on effective date or publication date of legal transaction data of invalid patent.
Login to view more 
Login to view more