Unlock instant, AI-driven research and patent intelligence for your innovation.

Naphthyridininones as AURORA kinase inhibitors

A compound and composition technology, applied in the field of naphthyridone compound and its pharmaceutically active drug, can solve the problem that the role of meiosis has not been studied in detail

Inactive Publication Date: 2014-09-03
MERCK PATENT GMBH
View PDF8 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Recently, there have been reports of small molecule inhibitors of Aurora kinases, but their effects on meiosis have not yet been studied in detail (Arora et al., J.Pharm.and Exptl.Therapeutics (2005), 315(3) :971-79)

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
  • Naphthyridininones as AURORA kinase inhibitors
  • Naphthyridininones as AURORA kinase inhibitors
  • Naphthyridininones as AURORA kinase inhibitors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0271] N-(4-Aminophenyl)-2-fluoro-benzoamide

[0272]

[0273] To a solution of N-Boc-1,4-phenylenediamine (1.0 g) in DCM (10 mL) was added triethylamine (1.1 eq., 971.78 mg) and 2-fluorobenzoyl chloride (1.1 eq., 837.56 mg ). After stirring for 30 minutes a precipitate formed. The precipitate (1.5 g) was filtered off and dried. It was suspended in DCM (5 mL) and trifluoroacetic acid (15 mL) and stirred for 15 minutes. The solvent was removed, the residue was dissolved in ethyl acetate / water, and the pH was adjusted to 10 with potassium carbonate solution. The ethyl acetate layer was separated and the aqueous layer was extracted with more ethyl acetate. The organic layers were combined, washed once with water, and dried over magnesium sulfate. The product (720 mg) was obtained after concentration, which was used in the next reaction without further purification. LCMS [231.2 (M+1)].

Embodiment 2

[0275] N-(5-Amino-pyrimidin-2-yl)-benzoamide

[0276]

[0277] To a solution of 2-amino-5-nitropyrimidine (1.0 g) in DCM (10 mL) was added triethylamine (1.1 eq) and benzoyl chloride (1.1 eq.). After 30 minutes a precipitate (1.1 g) was obtained which was filtered off and dried. The solid was dissolved in methanol (30 mL) and hydrogenated overnight at 30 psi in the presence of Pd / C (100 mg). The catalyst was filtered off through a pad of Celite. Methanol was removed and the crude product (820 mg) was used in the next reaction without further purification. LCMS [215.2 (M+1)].

Embodiment 3

[0279] N-(4-Aminophenyl)-3-fluoro-benzoamide

[0280]

[0281] Following the method described in Example 1, the title compound (910 mg) was synthesized from N-Boc-1,4-phenylenediamine (1.0 g), 1.1 eq. triethylamine and 3-benzoyl chloride (1.1 eq). LCMS [231.2 (M+1)].

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 discloses naphthyridone derivative compounds that inhibit Aurora kinase, pharmaceutical compositions containing these compounds and methods for synthesizing these compounds. These compounds are useful in the treatment of proliferative diseases associated with unregulated and / or disturbed Aurora kinases, such as cancer, psoriasis, viral and bacterial infections, inflammatory diseases and autoimmune diseases.

Description

technical field [0001] The present invention relates to naphthyridone compounds and their use as pharmaceutically active agents which inhibit protein kinases, especially Aurora kinases, thereby inhibiting abnormal cell proliferation and growth. Background of the invention [0002] Protein kinases represent a large family of proteins that play central roles in regulating a wide variety of cellular processes, maintaining control over cellular functions. These kinases include Akt, Axl, Aurora A, Aurora B, Aurora C, dyrk2, epha2, fgfr3, flt-3, vegfr3, igf1r, IKK2, JNK3, Vegfr2, MEK1, MET, P70s6K, Plk1, RSK1, Src, TrkA, Zap70, cKit, bRaf, EGFR, Jak2, PI3K, NPM-Alk, c-Abl, BTK, FAK, PDGFR, TAK1, LimK, Flt3, Flt1, PDK1 and Erk. Inhibition of these kinases has become an important therapeutic target. [0003] Many diseases are associated with abnormal cellular responses triggered by protein kinase-mediated events. These diseases include cancers such as acute and chronic myelogenou...

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): C07D471/04A61K31/436A61P35/00
CPCA61K31/436C07D471/04A61K45/06A61P1/16A61P13/12A61P17/06A61P19/02A61P19/04A61P27/02A61P31/04A61P31/12A61P35/00A61P37/00A61P37/06A61P7/02A61P9/10A61P9/14A61K2300/00A61K31/4375
Inventor Y·肖X·陈S·R·卡拉B·R·胡克A·E·萨顿A·古托普鲁斯
Owner MERCK PATENT GMBH