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US 7,842,820 B2Granted
Sulfonylpyrroles
Assignee4Sc AG
InventorsThomas Maier, Thomas Beckers, Thomas Baer, Petra Gimmnich, Frank Dullweber, Matthias Vennemann
Life of this patent
Estimating the term…
Abstract
Compounds of the formula I in which the substitutents have the definitions provided in the specification, are novel, effective HDAC inhibitors.
Claims15
A compound of formula I
- in which
- R1 is hydrogen, 1-4C-alkyl, halogen, or 1-4C-alkoxy,
- R2 is hydrogen or 1-4C-alkyl,
- R3 is hydrogen or 1-4C-alkyl,
- R4 is hydrogen, 1-4C-alkyl, halogen, or 1-4C-alkoxy,
- R5 is hydrogen, 1-4C-alkyl, halogen, or 1-4C-alkoxy,
- R6 is -T1-Q1, in which
- T1 is a bond, or 1-4C-alkylene,
- Q1 is Ar1, in which
- Ar1 is phenyl, or R61- and/or R62-substituted phenyl, in which
- R61 is 1-4C-alkyl, or -T2-N(R611)R612, in which
- either
- T2 is a bond, and
- R611 is hydrogen, 1-4C-alkyl, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl, phenyl-1-4C-alkyl, or Har1-1-4C-alkyl, in which
- Har1 is optionally substituted by R6111 and/or R6112, and is a monocyclic or fused bicyclic 5- to 10-membered unsaturated heteroaromatic ring comprising one to three heteroatoms, each of which is selected from the group consisting of nitrogen, oxygen and sulfur, in which
- R6111 is halogen, or 1-4C-alkyl,
- R6112 is 1-4C-alkyl, and
- R612 is hydrogen, 1-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl or hydroxy-2-4C-alkyl,
- or
- T2 is 1-4C-alkylene, or 2-4C-alkylene interrupted by oxygen, and
- R611 is hydrogen, 1-4C-alkyl, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl, phenyl-1-4C-alkyl, or Har1-1-4C-alkyl, in which
- Har1 is optionally substituted by R6111 and/or R6112, and is a monocyclic or fused bicyclic 5- to 10-membered unsaturated heteroaromatic ring comprising one to three heteroatoms, each of which is selected from the group consisting of nitrogen, oxygen and sulfur, in which
- R6111 is halogen, or 1-4C-alkyl,
- R6112 is 1-4C-alkyl, and
- R612 is hydrogen, 1-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl or hydroxy-2-4C-alkyl,
- or R611 and R612 together and with inclusion of the nitrogen atom, to which they are bonded, form a heterocyclic ring Het1, in which
- Het1 is morpholino, thiomorpholino, S-oxo-thiomorpholino, S,S-dioxo-thiomorpholino, piperidino, pyrrolidlino, piperazino, 4N-(1-4C-alkyl)-piperazino, imidazolo, pyrrolo or pyrazolo,
- R62 is 1-4C-alkyl, 1-4C-alkoxy, halogen, cyano, 1-4C-alkoxy-1-4C-alkyl, 1-4C-alkylcarbonylamino, or 1-4C-alkylsulphonylamino,
- R7 is hydroxyl, or Cyc1, in which
- Cyc1 is a ring system of formula Ia
- in which
- A is C (carbon),
- B is C (carbon),
- R71 is hydrogen, halogen, 1-4C-alkyl, or 1-4C-alkoxy,
- R72 is hydrogen, halogen, 1-4C-alkyl, or 1-4C-alkoxy,
- M with inclusion of A and B is either a ring Ar2 or a ring Har2, in which Ar2 is a benzene ring,
- Har2 is a monocyclic 5- or 6-membered unsaturated heteroaromatic ring comprising one to three heteroatoms, each of which is selected from the group consisting of nitrogen, oxygen and sulfur,
- or a salt thereof.
35 more elements
A compound which is selected from the group consisting of
- (E)-N-Hydroxy-3-[1-(toluene-4-sulfonyl)-1)-H-pyrrol-3-yl]-acrylamide,
- N-Hydroxy-3-(1-phenylmethanesulfony1H-pyrrol-3-yl)-acrylamide,
- (E)-3-[1-(4-Dimethylamino-benzenesulfonyl)-1H-pyrrol-3-yl]-N-hydroxy-acrylamide,
- (E)-N-(2-Amino-phenyl)-3-[1-(toluene-4-sulfonyl)-1H-pyrrol-3-yl]-acrylamide,
- (E)-N-(2-Amino-phenyl)-3-(1-phenylmethanesulfonyl-1H-pyrrol-3-yl)-acrylamide,
- (E)-N-(2-Amino-phenyl)-3-[1-(4-dimethylamino-benzenesulfonyl)-1H-pyrrol-3-yl]-acrylamide,
- (E)-N-Hydroxy-3-(1-[4-(([2-(1H-indol-2-yl)-ethyl]-methyl-amino)-methyl)-benzene sulfonyl]-1 H-pyrrol-3-yl)-acrylamide,
- (E)-3-[1-(4-Dimetylaminomethyl-benzenesulfonyl-1H-pyrrol-3-yl]-N-hydroxy-acrylamide,
- (E)-N-Hydroxy-3-[1-(4-{[(pyridin-3-ylmethyl)-amino]-methyl}-benzenesulfonyl)-1H-pyrrol-3-yl]-acrylamide,
- (E)-N-Hydroxy-3-[1-(4-{[(1H-indol-3-ylmethyl)-amino]-methyl}-benzenesulfonyl)-1H-pyrrol-3-yl]-acrylamide,
- (E)-3-{1-[4-(Benzylamino-methyl)-benzenesulfonyol]-1H-pyrrol-3-yl}-N-hydroxy-acrylamide,
- (E)-N-Hydroxy-3-{1-[4-(isobutylamino-methyl)-benzenesulfonyl]-1H-pyrrol-3-yl}-acrylamide,
- (E)-N-Hydroxy-3-[1-(4-{[(1H-indol-5-ylmethyl)-amino]-methyl}-benzenesulfonyl)-1H-pyrrol-3-yl]-acrylamide,
- (E)-N-Hydroxy-3-[1-(4-{[(pyridin-4-ylmethyl)-amino]-methyl}-benzenesulfonyl)-1H-pyrrol-3-yl]-acrylamide,
- (E)-3-[1-(4-Aminomethyl-benzenesulfonyl-1H-pyrrol-3-yl]-N-hydroxy-acrylamide,
- (E)-N-Hydroxy-3-[1-(4-morpholin-4-ylmethyl-benzenesulfonyl)-1H-pyrrol-3-yl]-acrylamide,
- (E)-N-Hydroxy-3-{1-[4-({(2-hydroxy-ethyl-[2-(1H-indol-2-yl)-ethyl]-amino}-methyl)-benzenesulfonyl]-1H-pyrrol-3-yl}-acrylamide,
- and the salts thereof.
15 more elements
Dependencies are inferred from the claim text.