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US 2010/0075946 A1Published application
Novel thiophene derivatives
AssigneeActelion Pharmaceuticals Ltd.
InventorsMartin Bolli, David Lehmann, Boris Mathys, Claus Mueller, Jörg Velker
Life of this patent
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Abstract
The invention relates to novel thiophene derivatives, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunosuppressive agents.
Claims20
A compound selected from the group consisting of thiophenes of the Formula (I),
- wherein
- R1 represents hydrogen, lower alkyl, lower alkoxy, or halogen;
- R2 represents hydrogen, lower alkyl, lower alkoxy, or halogen;
- R3 represents hydrogen, hydroxy-lower alkyl, 2,3-dihydroxypropyl, di-(hydroxy-lower alkyl)-lower alkyl, —CH2—(CH2)k—NR31R32, (azetidine-3-carboxylic acid)-1-yl-methyl, (azetidine-3-carboxylic acid lower alkylester)-1-yl-methyl, 2-[(azetidine-3-carboxylic acid)-1-yl]-ethyl, 2-[(azetidine-3-carboxylic acid lower alkylester)-1-yl]-ethyl, 3-[(azetidine-3-carboxylic acid)-1-yl]-propyl, 3-[(azetidine-3-carboxylic acid lower alkylester)-1-yl]-propyl, (pyrrolidine-3-carboxylic acid)-1-yl-methyl, (pyrrolidine-3-carboxylic acid lower alkylester)-1-yl-methyl, (pyrrolidine-2-carboxylic acid)-1-yl-methyl, (pyrrolidine-2-carboxylic acid lower alkylester)-1-yl-methyl, 2-[(pyrrolidine-3-carboxylic acid)-1-yl]-ethyl, 2-[(pyrrolidine-3-carboxylic acid lower alkylester)-1-yl]ethyl, 2-[(pyrrolidine-2-carboxylic acid)-1-yl]-ethyl, 2-[(pyrrolidine-2-carboxylic acid lower alkylester)-1-yl]ethyl, 3-[(pyrrolidine-3-carboxylic acid)-1-yl]-propyl, 3-[(pyrrolidine-3-carboxylic acid lower alkylester)-1-yl]-propyl, 3-[(pyrrolidine-2-carboxylic acid)-1-yl]-propyl, 3-[(pyrrolidine-2-carboxylic acid lower alkylester)-1-yl]-propyl, —CH2—(CH2)n—CONR31R32, —CO—NHR31, 1-(1-(3-carboxy-azetidinyl))-2acetyl, 1-(1-(2-carboxy-pyrrolidinyl))-2-acetyl, 1-(1-(3-carboxy-pyrrolidinyl))-2-acetyl, 1-(1-(3-carboxy-azetidinyl))-3-propionyl, 1-(1-(2-carboxy-pyrrolidinyl))-3-propionyl, 1-(1-(3-carboxy-pyrrolidinyl))-3-propionyl, —(CH2)nCH(OH)—CH2—NR31R32, hydroxy, lower alkoxy, fluoro-lower alkoxy, hydroxy-lower alkoxy, di-(hydroxy-lower alkyl)-lower alkoxy, 1-glyceryl, 2-glyceryl, 2-hydroxy-3-methoxy-propoxy, —OCH2—(CH2)m—NR31R32, 2-pyrrolidin-1-yl-ethoxy, 3-pyrrolin-1-yl-propoxy, 2-piperazin-1-yl-ethoxy, 2-[4-(lower alkyl)-piperazin-1-yl]ethoxy, 2-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-ethoxy, 3-piperazin-1-yl-propoxy, 3-[4-(lower alkyl)-piperazin-1-yl]-propoxy, 3-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-propoxy, 2-morpholin-4-yl-ethoxy, 3-morpholin-4-yl-propoxy, 2-[(azetidine-3-carboxylic acid)-1-yl]-ethoxy, 2-[(azetidine-3-carboxylic acid lower alkylester)-1-yl]ethoxy, 2-[(pyrrolidine-3-carboxylic acid)-1-yl]-ethoxy, 2-[(pyrrolidine-3-carboxylic acid lower alkylester)-1-yl]-ethoxy, 2-[(pyrrolidine-2-carboxylic acid)-1-yl]-ethoxy, 2-[(pyrrolidine-2-carboxylic acid lower alkylester)-1-yl]-ethoxy, 2-[(2-hydroxy-pyrrolidine)-1-yl]-ethoxy, 2-[(3-hydroxy-pyrrolidine)-1-yl]-ethoxy, 3-[(azetidine-3-carboxylic acid)-1-yl]-propoxy, 3-[(azetidine-3-carboxylic acid lower alkylester)-1-yl]-propoxy, 3-[(pyrrolidine-3-carboxylic acid)-1-yl]-propoxy, 3-[(pyrrolidine-3-carboxylic acid lower alkylester)-1-yl]-propoxy, 3-[(pyrrolidine-2-carboxylic acid)-1-yl]-propoxy, 3-[(pyrrolidine-2-carboxylic acid lower alkylester)-1-yl]-propoxy, 3-[(2-hydroxy-pyrrolidine)-1-yl]-propoxy, 3-[(3-hydroxy-pyrrolidine)-1-yl]-propoxy, 2-amino-3-hydroxy-2-hydroxymethyl-propoxy, —O—CH2—CONR31R32, 1-(1-(3-carboxy-azetidinyl))-1-oxo-2-ethoxy, 1-(1-(pyrrolidine-2-carboxylic acid)-1-yl)-1-oxo-2-ethoxy, 1-(1-(pyrrolidine-3-carboxylic acid)-1-yl)-1-oxo-2-ethoxy, 3-carbamoyl-propoxy, 3-(lower alkylcarbamoyl)propoxy, 3-(2-hydroxyethylcarbamoyl)propoxy, —OCH2—CH(OH)—CH2—NR31R32, 3-[(azetidine-3-carboxylicacid)-1-yl]-2-hydroxypropoxy, 3-[(azetidine-3-carboxylic acid lower alkylester)-1-yl]-2-hydroxypropoxy, 2-hydroxy-3-[(pyrrolidine-3-carboxylic acid)-1-yl]-propoxy, 2-hydroxy-3-[(pyrrolidine-3-carboxylic acid lower alkylester)-1-yl]-propoxy, 2-hydroxy-3-[(pyrrolidine-2-carboxylic acid)-1-yl]-propoxy, 2-hydroxy-3-[(pyrrolidine-2-carboxylic acid lower alkylester)-1-yl]-propoxy, 2-hydroxy-3-[(2-hydroxy-pyrrolidine)-1-yl]-propoxy, 2-hydroxy-3-[(3-hydroxy-pyrrolidine)-1-yl]-propoxy, 2-hydroxy-3-pyrrolidin-1-yl-propoxy, 2-hydroxy-3-piperazin-1-yl-propoxy, 2-hydroxy-3-[4-(lower alkyl)-piperazin-1-yl]-propoxy, 2-hydroxy-3-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-propoxy, 2-hydroxy-3-morpholin-4-yl-propoxy, —NR31R32, —NHCO—R31, —CH2—(CH2)k—NHSO2R33, —(CH2)nCH(OH)—CH2—NHSO2R33, —OCH2—(CH2)m—NHSO2R33, —OCH2—CH(OH)—CH2—NHSO2R33, —CH2—(CH2)k—NHCOR34, —(CH2)nCH(OH)—CH2—NHCOR34, —OCH2—(CH2)m—NHCOR34, or —OCH2—CH(OH)—CH2—NHCOR34;
- R31 represents hydrogen, methyl, ethyl, 1-propyl, 2-propyl, 2-hydroxyethyl, 2-hydroxy-1-hydroxymethyl-ethyl, 2-lower alkoxyethyl, 3-hydroxypropyl, 3-lower alkoxypropyl, 2-aminoethyl, 2-(lower alkylamino)ethyl, 2-(di-(lower alkyl)amino)ethyl, carboxymethyl, lower alkylcarboxymethyl, 2-carboxyethyl, or 2-(lower alkylcarboxy)ethyl;
- R32 represents hydrogen or methyl;
- R33 represents methyl, ethyl, propyl, isopropyl, butyl, 2-hydroxyethyl, 2-methoxyethyl, methylamino, ethylamino, propylamino, isopropylamino, n-butylamino, or dimethylamino;
- R34 represents hydroxymethyl, hydroxyethyl, aminomethyl, methylaminomethyl, dimethylaminomethyl, aminoethyl, 2-methylamino-ethyl, or 2-dimethylamino-ethyl;
- k represents the integer 1, 2, or 3;
- m represents the integer 1 or 2;
- n represents the integer 0, 1, or 2;
- R4 represents hydrogen, lower alkyl or halogen;
- R5 represents trifluoromethyl, methyl, ethyl, or propyl;
- R6 represents phenyl optionally mono- or di-substituted, wherein the substituents are independently selected from methyl, ethyl, trifluoromethyl, halogen and methoxy;
- or 2-, 3- or 4-pyridyl optionally substituted with methyl or methoxy;
- and
- R7 represents hydrogen, or methyl;
- or an optically pure enantiomer, a mixture of enantiomers, a racemate, a diastereomer, a mixture of diastereomers, a diastereomeric racemate, and a mixture of diastereomeric racemates, a salt, solvate, or a morphological form thereof.
15 more elements
17-20. (canceled)
Dependencies are inferred from the claim text.