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US 7,612,068 B2Granted
Aromatic oxyphenyl and aromatic sulfanylphenyl derivatives
AssigneeH. Lundbeck A/S
InventorsGarrick P. Smith, Gitte K. Mikkelsen, Kim Andersen, Daniel R. Greve, Jorgen Eskildsen
Life of this patent
Estimating the term…
Abstract
The present invention relates to compounds of formula I wherein the substituents are as defined below. The compounds of formula I are useful for the treatment of diseases such as schizophrenia, including both the positive and the negative symptoms of schizophrenia and other psychoses.
Claims23
A compound of the formula I
- wherein
- X is O, S or CR11R12, wherein R11 and R12 are each independently H or C1-6 alkyl;
- Y is O or S;
- R1, R2, R3 and R4 are each independently hydrogen;
- halogen;
- cyano;
- nitro;
- C1-6-alk(en/yn)yl;
- C1-6-alk(en/yn)yloxy;
- C1-6-alk(en/yn)ylsulfanyl;
- hydroxy;
- hydroxy-C1-6-alk(en/yn)yl;
- halo-C1-6-alk(en/yn)yl;
- halo-C1-6-alk(en/yn)yloxy;
- C3-8-cycloalk(en)yl;
- C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl;
- acyl;
- C1-6-alk(en/yn)yloxycarbonyl;
- C1-6-alk(en/yn)ylsulfonyl;
- aryl optionally substituted with a halogen, cyano, nitro, C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl, hydroxy, hydroxy-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)yloxy, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, acyl, C1-6-alk(en/yn)yloxycarbonyl or C1-6-alk(en/yn)ylsulfonyl;
- monocyclic heteroaryl optionally substituted with a halogen, cyano, nitro, C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl, hydroxy, hydroxy-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)yloxy, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, acyl, C1-6-alk(en/yn)yloxycarbonyl or C1-6-alk(en/yn)ylsulfonyl;
- or —NR13R14 wherein R13 and R14 are each independently hydrogen, C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6 alk(en/yn)yl or aryl, or R13 and R14 together with the nitrogen atom to which they are attached form a 3-7-membered heterocyclic ring which optionally contains one further heteroatom selected from O, S and N;
- R5 is aryl or monocyclic heteroaryl, optionally substituted with a halogen, cyano, nitro, C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl, hydroxy, hydroxy-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)yloxy, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, acyl, C1-6-alk(en/yn)yloxycarbonyl, C1-6-alk(en/yn)ylsulfonyl or —NR15R16 wherein R15 and R16 are each independently hydrogen, C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6 alk(en/yn)yl or aryl, or R15 and R16 together with the nitrogen atom to which they are attached form a 3-7-membered heterocyclic ring which optionally contains one further heteroatom selected from O, S and N;
- R6 is H, C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl or C3-8-cycloalk(en)yl, provided that when R6 is C1-6-alk(en/yn)yloxy or C1-6-alk(en/yn)ylsulfanyl then X is CR11R12, wherein R11 and R12 are each independently H or C1-6 alkyl;
- R7 and R8 are each independently H, C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl;
- R9 and R9′ are each independently H, C1-6-alk(en/yn)yl, hydroxy-C1-6-alk(en/yn)yl, C1-6alk(en/yn)ylsulfanyl-C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl;
- or
- R6 and R8 together with the atoms to which they are attached and the intervening carbon atom form a saturated 3-7 membered heterocyclic ring, and R7 is H, C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl, and R9 and R9′ are each independently H, C1-6-alk(en/yn)yl, hydroxy-C1-6-alk(en/yn)yl, C1-6 alk(en/yn)ylsulfanyl-C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl;
- or
- R7 and R8 together with the atoms to which they are attached form a saturated 3-7 membered heterocyclic ring, and R6 is H, C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl or C3-8-cycloalk(en)yl, provided that when R6 is C1-6-alk(en/yn)yloxy or C1-6-alk(en/yn)ylsulfanyl then X is CR11R12, wherein R11 and R12 are each independently H or C1-6 alkyl, and R9 and R9′ are each independently H, C1-6-alk(en/yn)yl, hydroxy-C1-6-alk(en/yn)yl, C1-6 alk(en/yn)ylsulfanyl-C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl;
- or
- R8 and R9 together with the atoms to which they are attached and the intervening carbon atom form a saturated 3-7 membered heterocyclic ring, and R6 is H, C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl or C3-8-cycloalk(en)yl, provided that when R6 is C1-6-alk(en/yn)yloxy or C1-6-alk(en/yn)ylsulfanyl then X is CR11R12, wherein R11 and R12 are each independently H or C1-6 alkyl, and R7 is H, C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl, and R9′ is H, C1-6-alk(en/yn)yl, hydroxy-C1-6-alk(en/yn)yl, C1-6 alk(en/yn)ylsulfanyl-C1-6-alk(en/yn)yl or C3-8-cycloalk(en)yl;
- R10 is H, C1-6-alk(en/yn)yl, aryl, aryl-C1-6-alk(en/yn)yl, wherein aryl is optionally substituted with a halogen, CF3, OCF3, CN, NO2 or C1-6-alk(en/yn)yl, or an alkali metal;
- or a pharmaceutically acceptable salt thereof.
31 more elements
Dependencies are inferred from the claim text.