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US 8,772,510 B2Granted
PDE10 modulators
AssigneeHoffmann-La Roche Inc.
InventorsStephan Bachmann, Alexander Flohr, Katrin Groebke Zbinden, Matthias Koerner, Bernd Kuhn, Jens-Uwe Peters, Markus Rudolph
Life of this patent
Estimating the term…
Abstract
The present invention relates to compounds of formula (I) wherein R1, R2, R3, R5, W, X, X1, Y, Y1, Z and Z1 are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit PDE10A and can be used in the treatment of CNS disorders such as schizophrenia, Alzheimer's disease, and Parkinson's disease.
Claims25
A compound of formula (I)
- wherein:
- X and X1 are each independently CR4 or N;
- Y and Y1 are each independently C or N;
- Z and Z1 are each independently CR6, NR7, N, O or S;
- R1 and R2 are each independently selected from hydrogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-haloalkyl, C1-C7-alkoxy-C1-C7-alkyl, heterocycloalkyl and C1-C7-alkyl optionally substituted by aryl or heteroaryl or
- R1 and R2, together with the nitrogen atom to which they are attached, form a bicyclic ring system or a heterocycloalkyl optionally substituted by 1 to 3 substituents independently selected from the group consisting of hydroxyl, halogen, C1-C7-alkyl, C1-C7-alkoxy, C1-C7-haloalkyl and oxo;
- R3 is hydrogen or C1-C7-alkyl;
- R4 is hydrogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-haloalkyl or halogen;
- R5 is aryl or heteroaryl each of which is optionally substituted by C1-C7-alkyl, C3-C8-cycloalkyl, halogen, C1-C7-haloalkyl, C1-C7-alkoxy, hydroxyl, C1-C7-hydroxyalkyl, C1-C7-alkoxyalkyl, acetyl, cyano, or amino optionally substituted by one or two C1-C7-alkyl groups;
- R6 is hydrogen, halogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-alkoxy, C1-C7-haloalkyl, C1-C7-alkoxyalkyl, heterocycloalkyl, aryl, heteroaryl, or C1-C7-alkyl optionally substituted by aryl, heteroaryl, heterocycloalkyl, or cycloalkyl;
- or
- R5 and R6, together with the Y1 and Z atom to which they are attached, form aryl or heteroaryl each of which is optionally substituted by C1-C7 alkyl, halogen, C1-C7-alkoxy, or C1-C7-haloalkyl;
- R7 is hydrogen, halogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-alkoxy, C1-C7-haloalkyl, C1-C7 alkoxyalkyl, heterocycloalkyl, aryl, heteroaryl, or C1-C7-alkyl optionally substituted by aryl, heteroaryl, heterocycloalkyl, or cycloalkyl;
- or
- R5 and R7, together with the Y1 and Z atom to which they are attached, form aryl or heteroaryl each of which is optionally substituted by C1-C7 alkyl, halogen, C1-C7-alkoxy, or C1-C7 haloalkyl;
- and
- W is ethylene which is optionally substituted by C1-C7 alkyl.
14 more elements
A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I)
- wherein:
- X and X1 are each independently CR4 or N;
- Y and Y1 are each independently C or N;
- Z and Z1 are each independently CR6, NR7, N, O or S;
- R1 and R2 are each independently selected from hydrogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-haloalkyl, C1-C7-alkoxy-C1-C7-alkyl, heterocycloalkyl and C1-C7-alkyl optionally substituted by aryl or heteroaryl;
- or
- R1 and R2, together with the nitrogen atom to which they are attached, form a bicyclic ring system or a heterocycloalkyl optionally substituted by 1 to 3 substituents independently selected from the group consisting of hydroxyl, halogen, C1-C7-alkyl, C1-C7-alkoxy, C1-C7-haloalkyl and oxo;
- R3 is hydrogen or C1-C7-alkyl;
- R4 is hydrogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-haloalkyl or halogen;
- R5 is aryl or heteroaryl each of which is optionally substituted by C1-C7-alkyl, C3-C8-cycloalkyl, halogen, C1-C7-haloalkyl, C1-C7-alkoxy, hydroxyl, C1-C7-hydroxyalkyl, C1-C7-alkoxyalkyl, acetyl, cyano, or amino optionally substituted by one or two C1-C7-alkyl groups;
- R6 is hydrogen, halogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-alkoxy, C1-C7-haloalkyl, C1-C7-alkoxyalkyl, heterocycloalkyl, aryl, heteroaryl, or C1-C7-alkyl optionally substituted by aryl, heteroaryl, heterocycloalkyl, or cycloalkyl;
- or
- R5 and R6, together with the Y1 and Z atom to which they are attached, form aryl or heteroaryl each of which is optionally substituted by C1-C7 alkyl, halogen, C1-C7-alkoxy, or C1-C7-haloalkyl;
- R7 is hydrogen, halogen, C1-C7-alkyl, C3-C8-cycloalkyl, C1-C7-alkoxy, C1-C7-haloalkyl, C1-C7-alkoxyalkyl, heterocycloalkyl, aryl, heteroaryl, or C1-C7-alkyl optionally substituted by aryl, heteroaryl, heterocycloalkyl, or cycloalkyl;
- or
- R5 and R7, together with the Y1 and Z atom to which they are attached, form aryl or heteroaryl each of which is optionally substituted by C1-C7 alkyl, halogen, C1-C7-alkoxy, or C1-C7-haloalkyl;
- and
- W is selected from ethylene which is optionally substituted by C1-C7 alkyl
- and a pharmaceutically acceptable carrier.
16 more elements
Dependencies are inferred from the claim text.