Heteroaromatic ring derivatives

A drug and compound technology, applied in the field of medicine, can solve problems such as short patent protection period and poor drug metabolism

Active Publication Date: 2021-04-27
郭守东 +1
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the poor drug metabolism of the JQ1 compound and the short patent protection period, it has not entered human clinical research

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
  • Heteroaromatic ring derivatives
  • Heteroaromatic ring derivatives
  • Heteroaromatic ring derivatives

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0069] The preparation method of the compound of the general formula (I) of the present invention comprises making the compound shown in the general formula (IV), its pharmaceutically acceptable salt or its easily hydrolyzed ester, and the compound shown in the general formula (V), its pharmaceutically acceptable Accepted salts, their readily hydrolyzable esters, or their isomers react,

[0070]

[0071] Among them, R 1 , R 2 , R 3 , A, B, C, D, E, m, n, p and q are as defined above.

[0072] The above-mentioned compounds of the present invention can be synthesized by the methods described in the following schemes and / or other techniques known to those of ordinary skill in the art, but are not limited to the following methods.

[0073] When n=1, the reaction scheme is:

[0074]

[0075] Reaction steps:

[0076] Step 1: Preparation of compound b

[0077] The raw material a was added into aqueous hydrobromic acid solution, refluxed overnight, and the reaction was alm...

Embodiment 1

[0112] Example 1 ((S)-6-(4-chlorophenyl)-1-methyl-4,11-dihydro-[1,2,4]-triazol[3',4':3,4 ][1, 4] Preparation of tert-butyl acetate (compound 1)-diaza[5,6-b]-4-indolyl)methyl)acetate

[0113] Step 1: Synthesis of 4-Bromo-5-nitro-1H-indole (Intermediate B)

[0114] Add raw material A (81 g, 0.5 mol) into 500 ml of hydrobromic acid aqueous solution, reflux overnight, and HPLC monitors that the reaction is almost complete. Cool down, adjust the pH to 7 with solid sodium carbonate, extract with ethyl acetate (100ml 3 times), and dry the organic phase to obtain 75g of intermediate B as a brown solid with a yield of 62.5%.

[0115] Step 2: Synthesis of (4-chloromethyl)-(5-nitro-1H-indole-4-)-methylketone (Intermediate D)

[0116] Dissolve intermediate B (70g, 0.29mol) in 500mL of tetrahydrofuran, cool down to -78°C under nitrogen protection, add n-butyllithium (2.5M, 140ml, 0.35mol) dropwise, raise the temperature to -40°C for 1 hour, and cool down again To -78°C, a tetrahydrof...

Embodiment 2

[0127] Example 2 ((S)-6-(4-chlorophenyl)-1-methyl-4,11-dihydro-[1,2,4]-triazol[3',4':3,4 ][1, Preparation of tert-butyl 4]-diaza-[5,6-b]-4-[1,8a-dihydro-imidazo[1,2-a]pyridine)acetate (compound 2)

[0128] The preparation method of reference example 1.

[0129] Molecular formula: C 24 h 23 N 6 ClO 2 Molecular weight: 462.16LC-MS(M+H) + :463

[0130] 1H NMR(DMSO)δ1.41(9H,s),δ2.37(3H,s),δ2.92(2H,d),δ4.89(1H,t),δ7.12(2H,d)7.30 (2H,s), δ7.45(2H,d), δ7.90(2H,d)

[0131] Example 2 ((S)-6-(4-chlorophenyl)-1-methyl-4,11-dihydro-[1,2,4]-triazol[3',4':3,4 ][1, Preparation of tert-butyl 4]-diaza-[5,6-b]-4-[1,3a-dihydro-pyrrole[1,5-a]pyridine)acetate (Compound 3)

[0132] The preparation method of reference example 1.

[0133] Molecular formula: C 24 h 23 N 6 ClO 2 Molecular weight: 462.16LC-MS(M+H) + :463

[0134] 1H NMR(DMSO)δ1.41(9H,s),δ2.37(3H,s),δ2.92(2H,d),δ5.01(1H,t),δ7.15(2H,d)7.33 (2H,s), δ7.45(2H,d), δ7.60(1H,t), δ7.90(1H,d)

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 present invention belongs to the technical field of medicine, and specifically relates to heteroaryl ring derivatives represented by general formula (I), their pharmaceutically acceptable salts, their easily hydrolyzed esters, their isomers and intermediates, and these compounds and their Intermediate preparation method. The heteroaryl ring derivatives of the present invention can be used to prepare medicines for treating and / or preventing tumors. where R 1 , R 2 , R 3 , A, B, C, D, E, m, n, p and q are as defined in the description.

Description

[0001] 1. Technical field [0002] The invention belongs to the technical field of medicine, and specifically relates to heteroaryl ring derivatives, pharmaceutically acceptable salts thereof, easily hydrolyzed esters, isomers and intermediates thereof, and preparation methods of heteroaryl ring derivatives and intermediates thereof . The heteroaromatic ring derivatives of the present invention can be used for cancer diseases including lung cancer, breast cancer, leukemia, skin cancer and lymphoma, and autoimmune diseases including rheumatoid arthritis, psoriasis, Crohn's disease and ulcerative colitis treatment and prevention of these diseases. [0003] 2. Background technology [0004] Epigenetics is a research hotspot in recent years. Epigenetics can be understood as the expression of different genes in different environments and situations, and finally achieve different physiological phenotypes, but the underlying genetic makeup has not changed. The mechanism of this sel...

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 Patents(China)
IPC IPC(8): C07D487/14C07D471/22A61K31/551A61K31/5517A61P35/00A61P35/02A61P37/02A61P19/02A61P17/06A61P1/00A61P1/04
CPCC07D471/22C07D487/14
Inventor 郭守东林佳玮
Owner 郭守东
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap