Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Small molecule compound

A technology of small molecule compounds and compounds, applied in digestive system, organic chemistry, drug combination, etc.

Inactive Publication Date: 2020-03-06
TECHNODERMA MEDICINES
View PDF8 Cites 11 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, many pharmaceutical companies have developed new drugs targeting JAK family members, but most of them focus on inhibiting JAK1 and JAK3, especially Tyk2 inhibitors are rarely reported

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
  • Small molecule compound
  • Small molecule compound
  • Small molecule compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0095] Embodiment 1, the reaction equation of synthetic compound TDM-180656 is as follows:

[0096]

[0097] Step 1: Example 56c

[0098] Compound 56a (1.2g, 8.0mmol), compound 56b (2.97g, 9.6mmol), Pd(dppf)Cl 2 (585mg, 0.8mmol), sodium carbonate (2.0g, 19.2mmol), 1,4-dioxane (30mL) and water (5mL) were added into a three-neck flask. Under the condition of the system water pump, the nitrogen was pumped and replaced three times. The reaction solution was reacted at 90° C. for 2 hours and then cooled. After the reaction was completed, the crude product was concentrated under reduced pressure and purified by column chromatography (eluent: petroleum ether / EtOAc=1 / 1) to obtain a colorless oily liquid compound 56c, namely compound 4-(2-chloropyrimidin-4-yl )-tert-butyl 5,6-dihydropyridine-1(2H)-carboxylate (1.9 g, 80% yield).

[0099] LCMS[M-55] + =240.0

[0100] 1 H NMR (400MHz, Chloroform-d) δ8.57 (d, J = 5.2Hz, 1H), 7.26 (d, J = 5.2Hz, 1H), 7.81 (s, 1H), 7.02 (s, 1H), 4...

Embodiment 2

[0119] Embodiment 2: The reaction equation of synthetic compound TDM-180658 is as follows:

[0120]

[0121] Add compound 56g (80mg, 0.31mmol), triethylamine (313mg, 3.1mmol) and N,N-dimethylformamide (5mL) into the reaction flask, and stir for about 6 minutes. Compound 58a, propionic acid (46 mg, 0.62 mmol) and HATU (177 mg, 0.47 mmol) were then added. The mixture was stirred at room temperature for 5 hours. After the reaction was completed, it was poured into water (2 mL), extracted with ethyl acetate (20 mL x 3). The organic layers were combined, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography (eluent: methanol / ethyl acetate=1 / 20) to obtain yellow solid compound 58, namely 1-( 4-(2-((1-Methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)piperidin-1-yl)propan-1-one (73.4 mg, 34% yield) .

[0122] LCMS[M+1] + =315.1

[0123] 1 H NMR (400MHz, Chloroform-d) δ8.31(d, J=5...

Embodiment 3

[0131] Embodiment 3, the general synthesis method of synthetic compound TDM-180662

[0132]

[0133] Step 1: Example 62b

[0134] Using compound 56g as the starting material, the synthesis steps are similar to those of compound 58. Compound 62b was obtained as light yellow solid compound 2-(4-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)piperidin-1-yl)-2- Oxoethyl acetate (90 mg, 32% yield).

[0135] LCMS[M+1] + =359.1

[0136] 1 H NMR (400MHz, Chloroform-d) δ8.32(d,J=4.8Hz,1H),7.82(s,1H),7.51(s,1H),6.89(s,1H),6.54(d,J= 4.8Hz,1H),4.65-4.85(m,3H),3.92(s,3H),3.74-3.85(m,1H),3.13-3.27(m,1H),2.70-2.86(m,2H),2.22 (s,3H),1.94-2.06(m,2H).

[0137] Step 2: Example 62 (TDM-180662)

[0138] To a solution of compound 62b (90 mg, 0.25 mmol) in tetrahydrofuran (5 mL) was added aqueous lithium hydroxide (1.5 mL, 1M). The mixture was stirred at room temperature for 3 hours. The reaction solution was diluted with water and extracted with ethyl acetate (15 mL*7). The organi...

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

No PUM Login to View More

Abstract

The invention provides a small molecule compound. The small molecule compound is characterized in that the small molecule compound is a compound shown in a structural formula in the specification, ora stereoisomer, a geometric isomer, a tautomer, a racemate, a hydrate, a solvate, a metabolite, and a pharmaceutically acceptable salt or pro-drug thereof, wherein X1 and X2 are selected from carbon or nitrogen; Z is carbon or nitrogen; n1 is 0 and 1; n2 and n3 are the same or different, and are 0 or any natural numbers; a cyclic group represented by G is a saturated heterocyclic ring; any one orseveral hydrogen atoms on the saturated heterocyclic ring are substituted by R; and R is selected from hydrogen, halogen, alkyl, substituted alkyl, amino, amine group, substituted amine group, carboxyl, amido, substituted amido, ester group, substituted carbonyl, cycloalkyl, substituted cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, substituted sulfonyl, and substituted sulfoxide group. The small molecule compound of the invention can be used to treat, prevent and alleviate autoimmune diseases and / or immune-related inflammatory skin diseases.

Description

technical field [0001] The present invention relates to the field of small molecule compounds, in particular to a small molecule compound and its derivatives that can be used to treat, prevent and alleviate autoimmune diseases and or immune-related inflammatory skin diseases. Background technique [0002] The JAK (Janus Kinase)-STAT (Signal Transducer and Activator of Transcription proteins) signal transduction pathway is the main pathway for the intracellular transduction of signals stimulated by the combination of inflammatory cytokines and receptors. JAKs is a family of intracellular non-receptor tyrosine kinases (Tyrosine Kinase), including four members JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2). JAKs are mainly expressed in hematopoietic cells, leukocytes and intestinal epithelial cells, and are responsible for mediating the signal transmission of various cytokines involved in inflammatory responses. When cytokines bind to cell surface receptors, JAKs are activated ...

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
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/14C07D403/12C07D403/14A61K31/506A61P29/00A61P37/06A61P17/06A61P17/00A61P19/02A61P1/00A61P25/28
CPCC07D401/14C07D403/12C07D403/14A61P29/00A61P37/06A61P17/06A61P17/00A61P19/02A61P1/00A61P25/28
Inventor 邢莉李冠群王晓磊蔡雨婷姜翔潘翔朱文浩汪杨王增全
Owner TECHNODERMA MEDICINES
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com