Pyrazolyl-amino-substituted pyrimidines and their use in the treatment of cancer

An amino and carbamoyl technology, applied in the field of new pyrazole derivatives, can solve problems such as doubtful effects

Inactive Publication Date: 2008-07-09
ASTRAZENECA AB
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Yet questions remain about the post-embryonic role of the Trk / neurotrophin axis (or channel)

Method used

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  • Pyrazolyl-amino-substituted pyrimidines and their use in the treatment of cancer
  • Pyrazolyl-amino-substituted pyrimidines and their use in the treatment of cancer
  • Pyrazolyl-amino-substituted pyrimidines and their use in the treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0241] (2R)-2-({5-chloro-2-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrimidin-4-yl}amino)-2-(4-fluoro Phenyl)ethanol

[0242] To a microwave vial (Personal Chemistry) was added (2R)-2-[(2,5-dichloropyrimidin-4-yl)amino]-2-(4-fluorophenyl)ethanol (Method 1, 250 mg, 0.83 mmol), 5-cyclopropyl-1H-pyrazol-3-amine (204 mg, 1.66 mmol), DIPEA (0.17 mL, 0.97 mmol) and n-butanol (2 mL). The reaction mixture was heated to 160°C and maintained for 5 hours. Solvent was removed. The white solid was purified by semi-preparative HPLC (Gilson) to give the title compound (43 mg, 13%). 1 H NMR (300MHz, DMSO-d6) δ0.76(m, 2H), 0.97(m, 2H), 1.87(m, 1H), 3.73-3.85(m, 2H), 5.22(m, 2H), 7.13( m, 2H), 7.47 (m, 2H), 7.97 (d, 1H), 8.28 (s, 1H).

Embodiment 2-8

[0244] According to a method similar to Example 1, the following compounds were synthesized by reaction of the appropriate pyrimidine or quinazoline (the production method of which is also listed) with the appropriate amine.

[0245] implement

example

name

1 H NMR

SM1

SM2

2

(2R)-2-({2-[(5-cyclopropyl

-1H-pyrazol-3-yl) amino] pyrimidine

Pyridin-4-yl}amino)-2-(4-fluoro

Phenyl)ethanol

(DMSO-d 6 +D 2 O): 0.63 (m, 2H),

0.93(m, 2H), 1.82(m, 1H), 3.67

(m, 2H), 4.98-5.17(m, 1H),

5.61-5.70(m, 1H), 6.30-6.62(m,

1H), 7.09(m, 2H), 7.32(m, 2H),

7.68-7.86 (m, 1H)

Method 2

5-cyclopropyl

-1H-pyrazole

-3-amine

3

(2R)-2-({2-[(5-cyclopropyl

-1H-pyrazol-3-yl)amino]-5

-(trifluoromethyl)pyrimidin-4-yl]

Amino}-2-(4-fluorophenyl) B

Alcohol

0.67(m, 2H), 0.94(m, 2H), 1.88

(m, 1H), 3.75H), 2H), 5...

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PUM

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Abstract

The present invention relates to novel compounds of formula I, and to pharmaceutical compositions thereof and methods of use thereof. These new compounds offer a cure for cancer.

Description

field of invention [0001] The present invention relates to novel pyrazole derivatives, their pharmaceutical compositions and their methods of use. Furthermore, the present invention relates to therapeutic methods for the treatment and prevention of cancer, and to the use of these pyrazole derivatives in the manufacture of medicaments for the treatment and prevention of cancer. Background of the invention [0002] Receptor tyrosine kinases (RTK's) are a subclass of protein kinases that play an important role in cell signaling and are involved in a variety of cancer-related processes including cell proliferation, survival, angiogenesis and metastasis. Currently up to 100 different RTk'S have been identified including tropomyosin-related kinases (Trk'S). [0003] Trk'S are high affinity receptors activated by a group of lytic growth factors called neurotrophins (NT). The Trk receptor family has three members: TrkA, TrkB and TrkC. In NT, there are (i) nerve growth factor (NGF...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D403/12A61K31/505A61P35/00
CPCC07D403/12A61P35/00A61P35/02A61P35/04A61P43/00
Inventor D·斯科特H·王T·王
Owner ASTRAZENECA AB
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