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US 12,655,174 B2Granted
Adenosine A3 receptor agonists, preparation methods and uses thereof
AssigneeZhejiang Vimgreen Pharmaceuticals, Ltd.
InventorsChongbo Hu, Jinqi Ye, Shuhua Pan, Ning Hu, Tingting Pan, Long Zhao, Zhengshu Chen, Sanxing Sun
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Abstract
The present application relates to novel compounds that have modulating or activating effect on the activity of adenosine A3 receptor, preparation methods for the series of compounds, pharmaceutical compositions of the series of compounds, and pharmaceutical uses of the series of compounds.
Claims5
The compound of formula IV:
- wherein
- R1a is selected from hydrogen and the following groups:
- C1-C2 alkyl, C1-C2 alkoxy, and cyclopropyl;
- R5 and R6 are each independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 alkoxy, C2-C3 alkenyl, and C2-C3 alkynyl, and m and n are each independently any integer from 0 to 2;
- and
- R1b, R4a, R4b, and Y are all hydrogen.
3 more elements
The compound of formula V:
- wherein
- R1a is selected from hydrogen and the following groups:
- C1-C2 alkyl, C1-C2 alkoxy, and cyclopropyl;
- R5 and R6 are each independently selected from halogen, cyano, C1-C2 alkyl, C1-C2 alkoxy, C2-C3 alkenyl, and C2-C3 alkynyl, and m is any integer from 0 to 2 and n is any integer from 0 to;
- and
- R1b, R4a, R4b and Y are all hydrogen.
3 more elements
A compound selected from:
- (2S,3S,4R,5R)-5-(6-(benzylamino)-2-(pyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-(benzylamino)-2-(5-chloropyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-(benzylamino)-2-(5-methylpyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-(benzylamino)-2-(5-cyanopyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-(benzylamino)-2-(5-fluoropyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-(benzylamino)-2-(5-methoxypyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-3,4-dihydroxyl-N-methyl-5-(2-(5-methylpyridin-3-yl)-6-((pyridin-2-ylmethyl)amino)-9H-purin-9-yl)-tetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-fluoropyridin-3-yl)-6-(((4-methylpyridin-2-yl)methyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(6-((3-chlorobenzyl)amino)-2-(5-fluoropyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-fluoropyridin-3-yl)-6-((3-methoxybenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-fluoropyridin-3-yl)-6-(((6-methylpyridin-2-yl)methyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-3,4-dihydroxyl-N-methyl-5-(6-(((6-methylpyridin-2-yl)methyl)amino)-2-(pyridin-3-yl)-9H-purin-9-yl)tetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-3,4-dihydroxyl-N-methyl-5-(6-((3-methylbenzyl)amino)-2-(pyridin-3-yl)-9H-purin-9-yl)tetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(6-(benzylamino)-2-(pyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-3,4-dihydroxyl-5-(2-(5-methoxypyridin-3-yl)-6-(((6-methylpyridin-2-yl))methyl)amino)-9H-purin-9-yl)-N-methyltetrahydrofuran-2-carboxamide;
- ((2S,3S,4R,5R)-5-(2-(5-chloropyridin-3-yl)-6-(((6-methylpyridin-2-yl))methyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(6-(benzylamino)-2-(5-chloropyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(6-(benzylamino)-2-(5-fluoropyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-chloropyridin-3-yl)-6-((((6-methoxypyridin-2-yl)methyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-chloropyridin-3-yl)-6-((3-methylbenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-fluoropyridin-3-yl)-6-((3-methylbenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-fluoropyridin-3-yl)-6-((3-methylbenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(6-(p-methylphenylmethylamino)-2-(5-chloropyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-(m-methylphenylmethylamino)-2-(5-chloropyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-(2-chloro-5-methylbenzylamino)-2-(5-chloropyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-(2-chloro-5-methylbenzylamino)-2-(5-chloropyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyl-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-((4-chloropyridin-2-yl)methylamino)-2-(pyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyl-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-((4-chloropyridin-2-yl)methylamino)-2-(5-fluoropyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyl-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-((4-chloropyridin-2-yl)methylamino)-2-(5-chloropyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyl-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-((4-chloropyridin-2-yl)methylamino)-2-(5-methoxypyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyl-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-3,4-dihydroxyl-N-methyl-5-(6-((4-methylpyridin-2-yl)methylamino)-2-(pyridin-3-yl)-9H-purin-9-yl)-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-(benzylamino)-2-(5-methoxypyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyl-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-3,4-dihydroxyl-N-methyl-5-(6-((4-methylpyridin-2-yl)methylamino)-2-(5-methylpyridin-3-yl)-9H-purin-9-yl)-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-(2-fluoro-5-methylbenzylamino)-2-(pyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyl-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-(2-fluoro-5-methylbenzylamino)-2-(5-fluoropyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyl-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-(2-fluoro-5-methylbenzylamino)-2-(5-methylpyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyl-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-(2-fluoro-5-methylbenzylamino)-2-(5-methoxypyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyl-tetrahydrofuran-2-formamide;
- (2S,3S,4R,5R)-5-(6-((((4-chloropyridin-2-yl)methyl)amino-2-(5-chloropyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-chloropyridin-3-yl)-6-((((4-methylpyridin-2-yl)methyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-chloropyridin-3-yl)-6-((3-methoxybenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-chloropyridin-3-yl)-6-((3,5-dimethylbenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-chloropyridin-3-yl)-6-((2-fluoro-5-methylbenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-chloropyridin-3-yl)-6-((2-fluoro-5-methylbenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(6-((3,5-dimethylbenzyl)amino)-2-(5-methylpyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-chloropyridin-3-yl)-6-(pyridin-2-methylamino)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-chloropyridin-3-yl)-6-(pyridin-4-ylmethylamino)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-chloropyridin-3-yl)-6-(pyridin-3-ylmethylamino)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(6-(benzylamino)-2-(5-chloropyridin-3-yl)-9H-purin-9-yl)-N-ethyl-3,4-dihydroxyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-chloropyridin-3-yl)-6-((6-methylpyridin-2-yl)methylamino)-9H-purin-9-yl)-3,4-dihydroxyl-N-(methyl-d3)-tetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-chloropyridin-3-yl)-6-(((4-methylpyridin-2-yl)methyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-chloropyridin-3-yl)-6-(((4-(trifluoromethyl)pyridin-2-yl)methyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-3,4-dihydroxyl-N-methyl-5-(6-(((6-methylpyridin-2-yl)methyl)amino)-2-(5-methylpyridin-3-yl)-9H-purin-9-yl)tetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5R)-5-(2-(5-chloropyridin-3-yl)-6-(((4-methoxypyridin-2-yl)methyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5S)-5-(6-((3,5-dimethylbenzyl)amino)-2-(pyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5S)-5-(6-((3,5-dimethylbenzyl)amino)-2-(5-methoxypyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5S)-5-(6-((3,5-dimethylbenzyl)amino)-2-(5-fluoropyridin-3-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5S)-3,4-dihydroxyl-5-(2-(5-methoxypyridin-3-yl)-6-((3-methylbenzylamino)-9H-purin-9-yl)-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5S)-3,4-dihydroxyl-N-methyl-5-(6-((pyridin-2-ylmethyl)amino)-2-(pyridin-3-yl)-9H-purin-9-yl)tetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5S)-5-(2-(5-fluoropyridin-3-yl)-6-((pyridin-2-ylmethyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5S)-5-(2-(5-chloropyridin-3-yl)-6-((pyridin-2-lymethyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5S)-3,4-dihydroxyl-5-(2-(5-methoxypyridin-3-yl)-6-((pyridin-2-ylmethyl)amino)-9H-purin-9-yl)-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5S)-3,4-dihydroxyl-N-methyl-5-(2-(pyridin-3-yl)-6-((((4-(trifluoromethyl)pyridin-2-yl)methyl)amino)-9H-purin-9-yl)tetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5S)-5-(2-(5-fluoropyridin-3-yl)-6-((((4-(trifluoromethyl)pyridin-2-yl)methyl)amino)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5S)-3,4-dihydroxyl-5-(2-(5-methoxypyridin-3-yl)-6-((((4-(trifluoromethyl)pyridin-2-yl)methyl)amino)-9H-purin-9-yl)-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5S)-3,4-dihydroxyl-5-(2-(5-methoxypyridin-3-yl)-6-((((4-(methylpyridin-2-yl)methyl)amino)-9H-purin-9-yl)-N-methyltetrahydrofuran-2-carboxamide;
- (2S,3S,4R,5S)-5-(6-(benzylamino)-2-(pyridin-2-yl)-9H-purin-9-yl)-3,4-dihydroxyl-N-methyltetrahydrofuran-2-carboxamide.
63 more elements
Dependencies are inferred from the claim text.