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

Novel pyrazolopyrimidines as cyclin dependent kinase inhibitors

a cyclin dependent kinase inhibitor and pyrazolopyrimidine technology, applied in the field of pyrazolo1, 5apyrimidine compounds, can solve the problems of increased cdk2 activity and poor overall survival

Active Publication Date: 2007-02-15
MERCK SHARP & DOHME LLC +1
View PDF10 Cites 15 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a novel class of pyrazolopyrimidine compounds that can inhibit the activity of cyclin dependent kinases (CDKs), which are important proteins involved in cell cycle regulation. These compounds can be used as pharmaceutical agents to treat diseases associated with CDKs, such as cancer. The invention also provides methods for preparing these compounds and pharmaceutical compositions containing them. The technical effects of this invention include the discovery of new compounds that can inhibit CDKs, as well as methods for making them.

Problems solved by technology

Their altered expression has been shown to correlate with increased CDK2 activity levels and poor overall survival.

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
  • Novel pyrazolopyrimidines as cyclin dependent kinase inhibitors
  • Novel pyrazolopyrimidines as cyclin dependent kinase inhibitors
  • Novel pyrazolopyrimidines as cyclin dependent kinase inhibitors

Examples

Experimental program
Comparison scheme
Effect test

examples 2-4

Preparative Examples 2-4

[0143] By essentially the same procedure set forth in Preparative Example 1, only substituting the nitrile shown in Column 2 of Table 2, the compounds in Column 3 of Table 2 were prepared:

TABLE 2Prep.Ex.Column 2Column 3233.10

example 4

Preparative Example 4

[0144]

[0145] 2-Carbomethoxycyclopentanone (6.6 ml, 0.05 mol) in THF (15 ml) was added dropwise to a vigorously stirred suspension of NaH (60% in mineral oil, 4 g, 0.1 mol) in THF (100 ml) at 0-10° C. When bubbling ceased, the reaction mixture was treated at the same temperature with CICOOMe (7.8 ml, 0.1 mol) in THF (15 ml). The resulted off-white suspension was stirred for 30 minutes at room temperature and 30 minutes under reflux. The reaction was monitored by TLC for disappearance of starting material. The reaction mixture was quenched with water carefully and partitioned between ethyl acetate and saturated solution of ammonium chloride in a funnel. Shaken and separated, the organic layer was washed with brine and dried over anhydrous sodium sulfate. Solvents were removed, and the residue was purified by flash chromatography, eluted with 5% and then 10% ethyl acetate in hexane. 9.4 g colorless oil was obtained with 94% yield. 1H NMR (CDCl3) δ 3.90(s, 3H), 3.73...

example 5

Preparative Example 5

[0146]

[0147] To lithium diisopropylamide solution in THF (2.0 N, 0.04 mol) at −65° C., was added dropwise 2,2-dicarbomethoxycyclopentanone (4 g, 0.02 mol) in THF (60 ml). The resulted reaction mixture was stirred at the same temperature before adding methyl chloroformate (1.54 ml, 0.02 mol). Reaction mixture stirred for an hour and poured into saturated ammonium chloride solution with some ice. This solution was extracted three times with ether, and the combined ethearal layers were dried over sodium sulfate. Solvents were removed in vacuo, and the residue was purified by flash chromatography, eluted with 30% increased to 50% ethyl acetate in hexane. 2.3 g yellowish oil was obtained with 58% yield. 1H NMR (CDCl3) δ 3.77(s, 6H), 3.32(t, 1H), 3.60-3.10(m, 4H).

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

PropertyMeasurementUnit
temperatureaaaaaaaaaa
temperatureaaaaaaaaaa
temperatureaaaaaaaaaa
Login to View More

Abstract

In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.

Description

[0001] This application claims benefit of priority from U.S. provisional patent applications, Ser. No. 60 / 408,027 filed Sep. 4, 2002, and Ser. No. 60 / 421,959 filed Oct. 29, 2002.FIELD OF THE INVENTION [0002] The present invention relates to pyrazolo[1,5-a]pyrimidine compounds useful as protein kinase inhibitors (such as for example, the inhibitors of the cyclin-dependent kinases, mitogen-activated protein kinase (MAPK / ERK), glycogen synthase kinase 3(GSK3beta) and the like), pharmaceutical compositions containing the compounds, and methods of treatment using the compounds and compositions to treat diseases such as, for example, cancer, inflammation, arthritis, viral diseases, neurodegenerative diseases such as Alzheimer's disease, cardiovascular diseases, and fungal diseases. BACKGROUND OF THE INVENTION [0003] Protein kinase inhibitors include kinases such as, for example, the inhibitors of the cyclin-dependent kinases (CDKs), mitogen activated protein kinase (MAPK / ERK), glycogen sy...

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(United States)
IPC IPC(8): A61K31/519C07D487/02C07D487/04
CPCC07D487/04A61P35/00A61P35/02A61P35/04
Inventor GUZI, TIMOTHYPARUCH, KAMILDWYER, MICHAELDOLL, RONALDGIRIJAVALLABHAN, VIYYOORMALLAMS, ALANALVAREZ, CARMENKEERTIKAR, KARTIKRIVERA, JOCELYNCHAN, TIN-YAUMADISON, VINCENTFISCHMANN, THIERRYDILLARD, LAWRENCETRAN, VINHHE, ZHENJAMES, RAYPARK, HAENGSOONPARADKAR, VIDYADHARHOBBS, DOUGLAS
Owner MERCK SHARP & DOHME LLC
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