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

Aminopyridazinone compounds as protein kinase inhibitors

A technology of compounds and solvates, applied in the field of aminopyridazinone compounds as protein kinase inhibitors, can solve problems such as immaturity of cells

Active Publication Date: 2017-04-19
JIANGSU HENGRUI MEDICINE CO LTD
View PDF2 Cites 19 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Patients with XLA have a normal population of pre-B cells in their bone marrow, but these cells fail to mature and enter the circulation

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
  • Aminopyridazinone compounds as protein kinase inhibitors
  • Aminopyridazinone compounds as protein kinase inhibitors
  • Aminopyridazinone compounds as protein kinase inhibitors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0158] Example 1. (R)-1-(1-acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-pyrrolo[2,3-d] Pyridazin-7(6H)-one

[0159]

[0160] Step 1A

[0161] To a solution of EtONa (160ml, 21% in EtOH, 0.49mmol) in EtOH (110ml) in an ice bath was added diethyl oxalate (64ml, 0.47mol). The mixture was stirred for 30 min. A solution of 1a (16 g, 0.15 mmol) in EtOH (30 ml) was added. The resulting mixture was stirred overnight at room temperature. After cooling in an ice bath, the suspension was filtered. The solid was washed with a little EtOH, then dissolved in water (380ml). The solution was acidified to pH~4 with HCl. A large amount of solid appeared which was filtered, washed with water and dried to give 1b (11.9g) as a yellow solid.

[0162] Step 1B

[0163]To a solution of 1b (2.3g, 7.5mmol) in EtOAc (120ml) at 60°C was added dropwise a solution of 1c (2.3g, 11.4mmol) in EtOAc (32ml). The mixture was refluxed for 4h. After cooling to room temperature, the solvent wa...

Embodiment 13

[0179] Example 13.1-(1-acryloyl-4-fluoropiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-pyrrolo[2,3-d]pyridazine -7(6H)-one

[0180]

[0181] Step 13A

[0182] 13a (2.2g) and NH 4 A mixture of OH (14 mL) in EtOH (33 mL) was stirred at 80 °C for 18 h in a sealed tube. The solvent was removed; the residue was dissolved in THF (30 mL) and EtOH (30 mL) and filled with Boc 2 O (2.46g). The mixture was stirred at room temperature for 20 h. The crude product was purified by silica gel chromatography to give white solid 13b (1.02g) and the undesired regioisomer (1.7g).

[0183] Step 13B

[0184] DAST (0.28 mL, 2.14 mmol) was added dropwise to a solution of 13b (0.68 g, 1.94 mmol) in DCM (20 mL) at -78 °C. The mixture was allowed to warm to room temperature overnight. NaHCO 3 The saturated solution was quenched and extracted with DCM. The organic extract was treated with Na 2 SO 4 Dry, filter and concentrate. The residue was purified by silica gel chromatography to give ...

Embodiment 14

[0199] Example 14. (R)-1-(1-acryloyl-5,5-difluoropiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-pyrrolo [2,3-d]pyridazin-7(6H)-one

[0200]

[0201] Step 14A

[0202] To a solution of 1b (271 mg) in EtOAc (12 ml) at 60 °C was added dropwise 14a (223 mg, the compound was prepared according to the procedure described by Anne Cochi et al. in Organic Letters, 2011, vol. 13, p. 4442-4445) in EtOAc (2ml) solution. The mixture was refluxed for 18h. After cooling to room temperature, the solvent was removed. The residue was purified by silica gel chromatography to afford 14b (76 mg) as a pale yellow oil.

[0203] Step 14B

[0204] Combine 14b (65mg) and Pd(OH) 2 / C (10wt%, 50mg) in the mixture of MeOH / THF (3 / 1ml) in H 2 Stir under a balloon for 20 h. The reaction mixture was filtered through a pad of celite, washed with EtOAc / MeOH, and concentrated. The residue was purified by silica gel chromatography to afford 14c (38 mg) as a white solid.

[0205] Step 14C

[0206] To...

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 disclosure provides a compound of formula (I) and the use thereof for the therapeutic treatment of human cancers including B-cell lymphoma and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis.

Description

technical field [0001] The present invention describes a series of novel compounds that exhibit potent inhibition of Bruton's tyrosine kinase and may thus provide potential therapeutic approaches for the treatment of human cancers, including B-cell lymphoma and Autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. Background technique [0002] Bruton's tyrosine kinase (Btk) is a non-receptor cytoplasmic tyrosine kinase belonging to the Tec kinase family, members of which also include Tec, Itk, Txk and Bmx. Most of these kinases are predominantly expressed in hematopoietic cells and play an important role in relaying signal transduction from cell surface receptors to direct cell development, differentiation and other functions (Berg JJ et al. Annual Review of Immunology, 2005; 23:549-600). Btk is critical for B cell development, differentiation, maturation and signaling (Mohamed AJ et al. Immunological Reviews, 2009; 228:58-...

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): A61K31/50C07D237/00
CPCC07D487/04A61P25/00A61P35/00A61P35/02A61P37/00A61P37/06A61K31/5025A61K31/50A61K31/505C07D237/00
Inventor 刘东张民生胡齐悦
Owner JIANGSU HENGRUI MEDICINE CO LTD
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