7-site substituted pyrrolotriazine compounds or pharmaceutically available salt thereof, and preparation method and use thereof

A technology of triazines and compounds, which is applied in the field of medicinal chemistry, can solve the problems of reporting PI3Kδ inhibitory activity, the large difference in properties between the mother nucleus and pyrrolotriazine, etc.

Inactive Publication Date: 2019-01-01
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this type of compound also has PI3Kδ selectivity reported [Murray et al., J Med Chem 55 (2012), p. 7686-7695], the properties of the core and pyrrolotriazine are quite different
How

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
  • 7-site substituted pyrrolotriazine compounds or pharmaceutically available salt thereof, and preparation method and use thereof
  • 7-site substituted pyrrolotriazine compounds or pharmaceutically available salt thereof, and preparation method and use thereof
  • 7-site substituted pyrrolotriazine compounds or pharmaceutically available salt thereof, and preparation method and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0057] As used herein, "alkyl" refers to straight or branched chain alkyl groups.

[0058] "Substituted" as used herein refers to substituting one or more hydrogen atoms. The halogen herein may be selected from at least one of F, Cl, Br and I, preferably at least one of F and Cl.

[0059] The present invention will be further described below in conjunction with the examples, but these examples are absolutely not intended to limit the present invention. In all examples, 1 H NMR was recorded by BrucherAM-400 and GEMINI-300 nuclear magnetic resonance instruments, chemical shifts were expressed in δ (ppm); mass spectra were recorded by MAT-95 mass spectrometer; silica gel for separation was 200-300 mesh.

[0060] Step a: Preparation of 4-cyano-5-methyl-1H-pyrrole-2-carboxylic acid ethyl ester (Aa2')

[0061]

[0062] Under an ice bath, to a solution of compound Aa1' (1.0 g, 6.5 mmol) and DMF (1.3 mL) in anhydrous acetonitrile (20 mL) was added dropwise chlorosulfonyl isocyan...

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 relates to 7-site substituted pyrrole [2,1-f][1,2,4] triazine compounds or pharmaceutically acceptable salts thereof, and a preparation method therefor and uses thereof. This kind of compound shows good PI3K inhibition activity, can effectively inhibit the activity of the PI3K kinase; and due to the introduction of 7-site groups, bioavailability and other pharmacokinetic properties have been greatly improved. In addition, the compounds in the present invention show an unpredictable high selectivity and strong inhibitory activity on PI3kdelta, accordingly, the compounds can be used to treat diseases associated with PI3K pathways, especially for resisting against cancers or treatment of tumors, leukemia and autoimmune diseases. After further optimization and screening,the compounds are expected to develop into new antitumor drugs.

Description

technical field [0001] The present invention relates to the field of medicinal chemistry, in particular to a 7-position substituted pyrrolotriazine compound or a pharmaceutically acceptable salt thereof, as well as a preparation method and use thereof. Background technique [0002] The PI3K-Akt-mTOR signaling pathway is one of the main pathways that transmit signals from receptor tyrosine kinases and G protein-coupled receptors, and plays an important role in a variety of cellular functions. Recent studies have found that in a variety of human tumors, multiple key node proteins in the PI3K-Akt-mTOR signaling pathway are overactivated due to mutations or amplifications in the encoding genes [Vivancod et al., Nat Rev Cancer 2 (2002) , pp. 489-501]. Among them, PI3K, as a bridge molecule linking extracellular signals and cell response effects, is a key factor in regulating cell growth, metabolism and survival, and its overactivation is closely related to the occurrence of vari...

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
IPC IPC(8): C07D487/04C07D519/00A61K31/53A61K31/5377A61P35/00A61P35/02A61P37/00
CPCC07D487/04C07D519/00A61P35/00A61P35/02A61P37/00A61K31/53A61K31/5377A61K31/5386C07D491/044
Inventor 杨春皓蒙凌华向皞月李京王祥谭村贺茜丁健陈奕
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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