Pyrazine compounds for the treatment of infectious diseases

A compound and alkyl technology, applied in anti-infective drugs, drug combination, organic chemistry, etc., can solve the problems that cannot be realized

Active Publication Date: 2017-09-26
F HOFFMANN LA ROCHE & CO AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most currently treated patients fail to achieve this goal

Method used

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  • Pyrazine compounds for the treatment of infectious diseases
  • Pyrazine compounds for the treatment of infectious diseases
  • Pyrazine compounds for the treatment of infectious diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0985] 3-(4-fluorophenyl)-N-phenyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazine-5-carboxamide

[0986]

[0987] The target compound was prepared according to the following scheme:

[0988]

[0989] Step 1: Preparation of tert-butyl N-(2-hydroxyethyl)-N-(1H-pyrazol-5-ylmethyl)carbamate (Compound 1b)

[0990] To a solution of 1H-pyrazole-5-carbaldehyde (Compound 1a, 54.0 g, 562.5 mmol) in MeOH (300 mL) was added 2-aminoethanol (41.2 g, 675 mmol), and the reaction mixture was stirred at 25°C for 1 hour. Then add NaBH at 0°C 4 (25.9 g, 675.0 mmol), the reaction mixture was stirred for an additional 1 hour. Add H to the reaction mixture 2 O (300mL) and Boc 2 O (147.1 g, 675.0 mmol), then the obtained mixture was stirred at room temperature for 12 hours, extracted with EtOAc (600 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography (eluting with 20%-50% EtOAc in petroleum ether) to obtain compound 1b...

Embodiment 2

[1004] N,3-Diphenyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazine-5-carboxamide

[1005]

[1006] The preparation of embodiment 2:

[1007] The title compound was prepared in a similar manner to Preparation Example 1, using phenylboronic acid instead of (4-fluorophenyl)boronic acid. Example 2 was obtained as a white solid (30 mg). LCMS (M+H + ): 319. 1 H NMR (400MHz, DMSO-d 6 )δppm 8.90(s,1H),7.85(s,1H),7.51-7.38(m,6H),7.30-7.20(m,3H),6.97(m,1H),4.95(s,2H),4.24( m,2H), 4.01(m,2H).

Embodiment 3

[1009] 3-(3-Fluorophenyl)-N-phenyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazine-5-carboxamide

[1010]

[1011] The preparation of embodiment 3:

[1012] The title compound was prepared in a similar manner to Preparation Example 1, using (3-fluorophenyl)boronic acid instead of (4-fluorophenyl)boronic acid. Example 3 was obtained as a white solid. LCMS (M+H + ): 337.1H NMR (400MHz, chloroform-d) δppm 7.75(s,1H),7.46-7.31(m,5H),7.18-6.97(m,4H),6.47(s,1H),4.91(s,2H ), 4.37(t, J=5.3Hz, 2H), 4.06(t, J=5.4Hz, 2H).

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Abstract

The present invention relates to compounds of the formula (I), or pharmaceutically acceptable salts, enantiomer or diastereomer thereof, wherein R1 to R4 are as described above. The compounds may be useful for the treatment or prophylaxis of hepatitis B virus infection.

Description

technical field [0001] The present invention relates to organic compounds for use in the treatment and / or prevention of mammals, in particular for the treatment of hepatitis B virus infection, their pharmaceutical activity, their preparation, pharmaceutical compositions containing them and their potential use as medicaments . [0002] The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof, [0003] [0004] where R 1 -R 4 , Y and Q are described below. The compounds of the present invention are useful in the treatment or prevention of hepatitis B virus infection. Background technique [0005] Hepatitis B virus (HBV) infection is an important public health problem worldwide, with approximately 30% of the world's population showing serological evidence of current or past infection. Despite the introduction of a safe and effective preventive vaccine against the virus in the early 1980s, it is ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D487/04C07D519/00A61K31/4985A61K31/506A61K31/5355A61K31/5377A61P31/20
CPCC07D487/04C07D519/00A61P1/16A61P31/00A61P31/12A61P31/20A61K31/4985
Inventor 胡泰山韩兴春寇步雨沈宏颜士翔张志森
Owner F HOFFMANN LA ROCHE & CO AG
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