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aminoimidazopyridazine

A group and alkyl technology, applied in the field of imidazopyridazine compounds, can solve the problems of activity and no indication

Inactive Publication Date: 2017-08-15
BAYER PHARMA AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0035] The above prior art does not show that the specific amino-substituted imidazopyridazine compounds of general formula (I) defined in the present invention will be so active as inhibitors of MKNK-1 kinase

Method used

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Experimental program
Comparison scheme
Effect test

no. 5 approach

[0165] According to the fifth embodiment of the first aspect, the present invention includes the compound of the above general formula (I), wherein:

[0166] represents a group selected from:

[0167]

[0168] wherein * indicates the point of attachment of said group to the rest of the molecule;

[0169] R1 represents C3-C6 cycloalkyl or -(CH2)-C3-C6 cycloalkyl, which is substituted one or more times by hydroxyl and which is optionally substituted by one or more substituents independently selected from the following:

[0170] A 3 to 6-membered heterocycloalkyl group linked by a spiro ring; an aryl group optionally substituted once or twice by R substituents independently of each other; an aryl group optionally substituted one or more times by R substituents independently of each other- C 1 -C 6 alkoxy;

[0171] R2 represents a hydrogen atom;

[0172] R3 represents a substituent selected from the following:

[0173] C 1 -C 6 Alkoxy, C 3 -C 6 Cycloalkoxy, C 3 -C ...

Embodiment 1

[0365](trans-3-{[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]amino}cyclobutyl)methanol

[0366]

[0367] 150 mg (0.56 mmol) 3-(1-benzofuran-2-yl)-6-chloroimidazo[1,2-b]pyridazine, 183.7 mg (1.34 mmol) in 4.0 mL butan-1-ol ) (trans-3-aminocyclobutyl)methanol and 415 mg (3.00 mmol) of potassium carbonate were stirred at 150° C. for 48 hours. Remove solvent. The residue was purified by HPLC to afford 6 mg (3%).

[0368] LC-MS (Method 2): R t = 0.90min; MS (ESIpos) m / z = 335 [M+H] + .

[0369] 1 H-NMR (400MHz, DMSO-d 6 ), δ[ppm]=2.03-2.12(2H), 2.28-2.37(2H), 2.38-2.46(1H), 3.55-3.61(2H), 4.32-4.43(1H), 4.63-4.69(1H), 6.73 -6.79(1H), 7.24-7.37(2H), 7.52-7.57(1H), 7.58-7.64(2H), 7.67-7.72(1H), 7.80-7.85(1H), 7.90-7.95(1H).

Embodiment 2

[0371] trans-3-({[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]amino}methyl)cyclobutanol

[0372]

[0373] 150mg (0.56mmol) of 3-(1-benzofuran-2-yl)-6-chloroimidazo[1,2-b]pyridazine, 183.7mg (1.34mmol) of trans-3-(aminomethyl ) cyclobutanol hydrochloride (1:1) and 415 mg (3.00 mmol) potassium carbonate were stirred in 4.0 mL butan-1-ol at 150° C. for 48 hours. Remove solvent. The residue was purified by HPLC to give 7.0 mg (4%).

[0374] LC-MS (Method 2): R t = 0.90min; MS (ESIpos) m / z = 335 [M+H] + .

[0375] 1 H-NMR (400MHz, DMSO-d 6 ), δ[ppm]=1.95-2.05(2H), 2.10-2.19(2H), 2.52-2.60(1H), 3.41-3.48(2H), 4.28-4.38(1H), 4.94-5.00(1H), 6.77 -6.82(1H), 7.21-7.35(3H), 7.54-7.57(1H), 7.59-7.65(1H), 7.67-7.73(1H), 7.78-7.84(1H), 7.90-7.95(1H).

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Abstract

The present invention relates to amino-substituted imidazopyridazine compounds of general formula (I), wherein A, R1, R2, R3, R4 and n are as defined in the claims, to processes for the preparation of said compounds, to methods useful for the preparation of said compounds Intermediate compounds of said compounds, to pharmaceutical compositions and combinations comprising said compounds, and to the use of said compounds as a single drug or in combination with other active ingredients for the preparation of pharmaceutical compositions which can be used for the treatment of Or to prevent diseases, especially hyperproliferative and / or angiogenic diseases.

Description

[0001] The present invention relates to amino-substituted imidazopyridazine compounds of general formula (I) as described and defined herein, processes for the preparation of the compounds, intermediate compounds useful in the preparation of the compounds, pharmaceutical compositions and combinations comprising the compounds, And the use of the compound as a single drug or in combination with other active ingredients for the preparation of a pharmaceutical composition, the pharmaceutical composition can be used to treat or prevent diseases, especially hyperproliferative diseases and / or angiogenesis diseases. Background technique [0002] The present invention relates to compounds that inhibit MKNK1 kinase (also known as MAP kinase-interacting kinase, Mnk1 ) and MKNK2 kinase (also known as MAP kinase-interacting kinase, Mnk2). Human MKNK comprises a set of four proteins encoded by two genes (gene symbols: MKNK1 and MKNK2) obtained by alternative splicing. The b-type lacks the M...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D487/04A61K31/4355A61P35/00
CPCC07D487/04C07D519/00A61K31/5025A61P29/00A61P35/00A61P35/02A61P37/02A61P43/00A61K45/06
Inventor L.佐恩K.艾斯V.舒尔策D.休兹尔F.皮尤勒P.利诺U.博默K.彼得森A.黑格巴思
Owner BAYER PHARMA AG