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US 8,575,193 B2Granted
N-substituted tetrahydroisoquinoline/isoindoline hydroxamic acid compounds
Assignee4Sc AG
InventorsThomas Maier, Thomas Beckers, Christian Hesslinger
Life of this patent
Estimating the term…
Abstract
Compounds of a certain formula (I) wherein R1, R2, R3, X, Y, r, s, t, u and v have the meanings as defined in the specification, and the salts, solvates and hydrates thereof are novel effective HDAC 6 inhibitors.
Claims17
A compound of formula I
- wherein
- R1 is
- R2 is H;
- R3 is hydrogen, —OR4, —NR5R6, or an optionally substituted alicyclic, heteroalicyclic, aromatic or heteroaromatic radical, wherein
- the alicyclic radical is a 3- to 6-membered monocyclic group,
- the heteroalicyclic radical is a 5- to 6-membered monocyclic group containing one or two heteroatoms, each of which is selected from the group consisting of nitrogen, oxygen and sulfur,
- the aromatic radical is phenyl or naphthyl,
- the heteroaromatic radical is a 5- to 6-membered monocyclic group or a 9- to 10-membered bicyclic group containing one or two heteroatoms, each of which is selected from the group consisting of nitrogen, oxygen and sulfur,
- and
- the substituents of the optionally substituted alicyclic, heteroalicyclic, aromatic or heteroaromatic radical are each selected from the group consisting of halogen, 1-4C alkyl, 1-4C alkoxy and phenyl;
- R4 is hydrogen, 1-4C alkyl or a substituted or unsubstituted alicyclic, heteroalicyclic, aromatic or heteroaromatic group, wherein each of these groups is as defined as in R3;
- R5 and R6 are each independently H or 1-4C alkyl;
- X is a single bond, —CH═CH—, —C≡C—, —NH—, oxygen or sulfur;
- Y is —NH—, oxygen or sulfur;
- r is 1 or 2,
- one of s and u is 0 and the other is 1,
- t is 0, 1, 2, 3, 4or 5, and
- v is 0, 1, 2, 3 or 4;
- or a salt thereof.
16 more elements
A compound, which is
- 9.1. N-Hydroxy-2-(indol-3-ylacetyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide
- 9.2. N-Hydroxy-2-(pyridin-2-ylacetyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide,
- 9.3. 2-(Cyclobutylcarbonyl)-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-6-carboxamide,
- 9.4. N6-Hydroxy-N2-methyl-3,4-dihydroisoquinoline-2,6(1H)-dicarboxamide,
- 9.5. N6-Hydroxy-N2-(3-methoxypropyl)-3,4-dihydroisoquinoline-2,6(1H)-dicarboxamide,
- 9.6. 3-Methoxypropyl-6-(hydroxycarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate,
- 9.7. N-Hydroxy-2-(3-pyridin-3-ylpropanoyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide,
- 9.8. N-Hydroxy-2-(pyridin-3-ylacetyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide,
- 9.9. 2-[4-(Dimethylamino)butanoyl]-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-6-carboxamide,
- 9.10. N-Hydroxy-2-[(2-methyl-1H-imidazol-1-yl)acetyl]-1,2,3,4-tetrahydroisoquinoline-6-carboxamide,
- 9.11. N-Hydroxy-2-[(2-methoxyethoxy)acetyl]-1,2,3,4-tetrahydroisoquinoline-6-carboxamide,
- 9.12. 2-Acetyl-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-6-carboxamide,
- 9.13. N-Hydroxy-2-(tetrahydrofuran-3-ylcarbonyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide,
- 9.14. N-Hydroxy-2-(pyridin-2-ylacetyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide,
- 9.15. N-Hydroxy-2-[(5-methoxy-1H-indol-2-yl)carbonyl]-1,2,3,4-tetrahydroisoquinoline-6-carboxamide,
- 9.16. N-Hydroxy-2-(cyclopropylcarbonyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide,
- 9.17. 2-But-2-ynoyl-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-7-carboxamide,
- 9.18. N-Hydroxy-2-(1H-indol-3-ylacetyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide,
- 9.19. N-Hydroxy-2-(pyridin-3-ylacetyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide,
- 9.20. N-Hydroxy-2-(tetrahydrofuran-3-ylcarbonyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide,
- 9.21. N-Hydroxy-2-(pyridin-2-ylacetyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide,
- 9.22. N7-Hydroxy-N2-(2-phenylethyl)-3,4-dihydroisoquinoline-2,7(1H)-dicarboxamide,
- 9.23. N-Hydroxy-2-(4-methylbenzoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide,
- 9.24. N-Hydroxy-2-[(5-methoxy-1H-indol-2-yl)carbonyl]-1,2,3,4-tetrahydroisoquinoline-7-carboxamide,
- 9.25. 2-Acetyl-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-7-carboxamide,
- 9.26. Pyridin-3-ylmethyl 5-(hydroxycarbamoyl)-1,3-dihydro-2H-isoindole-2-carboxylate,
- 9.27. N-Hydroxy-2-(quinolin-2-ylcarbonyl)isoindoline-5-carboxamide,
- 9.28. N-Hydroxy-2-(quinolin-6-ylcarbonyl)isoindoline-5-carboxamide,
- 9.29. N-Hydroxy-2-(isoquinolin-3-ylcarbonyl)isoindoline-5-carboxamide,
- 9.30. 2-(Biphenyl-4-ylcarbonyl)-N-hydroxyisoindoline-5-carboxamide,
- 9.31. N-Hydroxy-2-(3-pyridin-3-ylpropanoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide,
- 9.32. N7-Hydroxy-N2-(3-methoxypropyl)-3,4-dihydroisoquinoline-2,7(1H)-dicarboxamide,
- 9.34. 3-Methoxypropyl 7-(hydroxycarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate,
- 9.35. N7-Hydroxy-N2-methyl-3,4-dihydroisoquinoline-2,7(1H)-dicarboxamide,
- 9.36. 2-(Cyclobutylcarbonyl)-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-7-carboxamide,
- 9.37. N-Hydroxy-2-(1H-indol-5-ylcarbonyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide,
- 9.38. N-Hydroxy-2-[(2-methoxyethoxy)acetyl]-1,2,3,4-tetrahydroisoquinoline-7-carboxamide,
- 9.39. N-Hydroxy-2-[3-(2-methyl-1H-imidazol-1-yl)propanoyl]-1,2,3,4-tetrahydroisoquinoline-7-carboxamide,
- 9.40. Benzyl 6-(hydroxycarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate,
- 9.41. N-Hydroxy-2-(phenoxyacetyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide,
- 9.42. N-Hydroxy-2-(4-methylbenzoyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide,
- 9.43. N6-Hydroxy-N2-[2-(1H-indol-3-yl)ethyl]-3,4-dihydroisoquinoline-2,6(1H)-dicarboxamide,
- 9.44. N6-Hydroxy-N2-benzyl-3,4-dihydroisoquinoline-2,6(1H)-dicarboxamide,
- 9.45. N6-Hydroxy-N2-(2-phenoxyethyl)-3,4-dihydroisoquinoline-2,6(1H)-dicarboxamide, or
- 9.46. N-hydroxy-2-(1H-Indol-5-ylcarbonyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide,
- or a salt thereof.
43 more elements
Dependencies are inferred from the claim text.