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US 6,610,723 B2Granted
Imidazole derivatives
AssigneeHoffmann-La Roche Inc.
InventorsAlexander Alanine, Bernd Buettelmann, Marie-Paule Heitz Neidhart, Georg Jaeschke, Emmanuel Pinard, Rene Wyler
Life of this patent
Estimating the term…
Abstract
Novel imidazole derivatives are disclosed. These compounds have a good affinity to the NMDA (N-methyl-D-aspartate)-receptor subtype selective blockers, which have a key function in modulating neuronal activity and plasticity which makes them key players in mediating processes underlying development of CNS as well as learning and memory formation. These compounds are useful in the control or treatment of diseases mediated by this receptor.
Claims25
A compound of formula
- wherein
- A is phenyl, pyridin-2-yl, pyridin-3-yl, or piperidin-1-yl;
- R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, lower alkyl, cycloalkyl, lower alkenyl, trifluoromethyl, —O-trifluoromethyl, —S-trifluoromethyl, S-lower alkyl, lower alkoxy, —CHF2, —C(lower alkyl)F2, —OCHF2, phenyl, nitro, benzyloxy, hydroxy and amino, or alternatively, R1 and R2
- together with the carbon atoms to which they are attached in any adjacent positions from a group selected from —CH═CH—CH═CH—, —CH═CH—CH═N—, —(CH2)3—, —O—CH2—O—, —O—CF2—O—, —CH2—O—CH2— and —CH2CH2—O—;
- R3 is selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, phenyl, S-lower alkyl, amino, lower alkyl-amino, —NHC(O)-lower alkyl and hydroxy-lower alkyl;
- R4 and R5 are each independently selected from hydrogen and lower alkyl, or alternatively, R4 and R 5 together with the carbon atoms to which they are attached form the group —(CH2)4—;
- R6 and R6′ are each independently selected from hydrogen and lower alkyl;
- X is —N< or
- Y is ═N—, —NH—, —N═CH— or —CH═;
- Z is —CR7═, —N═, —NR7—, —N═CR7—, ═CH—N═C(R7)— or ═N—CH═CH—;
- R7 is hydrogen, —CH2OH or lower alkyl;
- n is 0, 1 or 2;
- m is 0 or 1;
- and
- the dotted line may be 1, 2 or 3 bonds;
- and pharmaceutically acceptable acid addition salts thereof.
13 more elements
A compound of formula
- wherein
- A is phenyl, pyridin-2-yl, pyridin-3-yl, or piperidin-1-yl;
- R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, lower alkyl, cycloalkyl, lower alkenyl, trifluoromethyl, —O-trifluoromethyl, —S-trifluoromethyl, S-lower alkyl, lower alkoxy, —CHF2, —C(lower alkyl)F2, —OCHF2, phenyl, nitro, benzyloxy, hydroxy and amino, or alternatively, R1 and R2
- together with the carbon atoms to which they are attached in any adjacent positions from a group selected from —CH═CH—CH═CH—, —CH═CH—CH═N—, —(CH2)3—, —O—CH2—O—, —O—CF2—O—, —CH2—O—CH2— and —CH2CH2—O—;
- the heterocyclic aromatic group
- in formula I is selected from the group consisting of
- R3 is selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, phenyl, S-lower alkyl, amino, lower alkyl-amino, —NHC(O)-lower alkyl and hydroxy-lower alkyl;
- R4 and R5 are each independently selected from hydrogen and lower alkyl, or alternatively, R4 and R5 together with the carbon atom to which they are attached form the group —(CH2)4—;
- R6 and R6′ are each independently selected from hydrogen and lower alkyl;
- and
- R7 is hydrogen, —CH2OH or lower alkyl;
- and pharmaceutically acceptable acid addition salts thereof.
9 more elements
A pharmaceutical composition comprising one or more compounds of formula I or a pharmaceutically acceptable salt thereof, and an inert carrier.
A process for preparing a compound of formula I comprising:
- reacting a compound of formula
- with a compound of formula
- to give a compound of formula
- wherein
- A is phenyl or pyridin-2 or 3-yl;
- R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, lower alkyl, trifluoromethyl, S-lower alkyl, lower alkoxy, —OCHF2, phenyl, nitro, benzyloxy, hydroxy and amino, or alternatively, R1 and R2
- together with the carbon atoms to which they are attached from a group selected from —(CH2)3—, —O—CH2—O—, —CH2—O—CH2— and —CH2CH2—O—;
- R3 is selected from the group consisting of hydrogen, lower alkyl, phenyl, S-lower alkyl, amino, lower alkyl-amino, —NHC(O)-lower alkyl and hydroxy-lower alkyl;
- R4 and R5 are each independently selected from hydrogen and lower alkyl, or alternatively, R4 and R5 together with the carbon atom to which they are attached form the group —(CH2)4—;
- R6 and R6′ are each independently selected from hydrogen and lower alkyl;
- R7 is hydrogen, —CH2OH or lower alkyl;
- and
- hal is Br or Cl.
10 more elements
A process for preparing a compound of formula I comprising:
- reacting a compound of formula
- with a compound of formula
- to give a compound of formula
- wherein
- A is phenyl or pyridin-2 or 3-yl;
- R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, lower alkyl, trifluoromethyl, S-lower alkyl, lower alkoxy, —OCHF2, phenyl, nitro, benzyloxy, hydroxy and amino, or alternatively, R1 and R2
- together with the carbon atoms to which they are attached from a group selected from —(CH2)3—, O—CH2—O—, —CH2—O—CH2— and —CH2CH2—O—;
- R3 is selected from the group consisting of hydrogen, lower alkyl, phenyl, S-lower alkyl, amino, lower alkyl-amino, —NHC(O)-lower alkyl and hydroxy-lower alkyl;
- R4 and R5 are each independently selected from hydrogen and lower alkyl, or alternatively, R4 and R5 together with the carbon atom to which they are attached form the group —(CH2)4—;
- R6 and R6′ are each independently selected from hydrogen and lower alkyl;
- and
- hal is Br or Cl.
9 more elements
A process for preparing a compound of formula I comprising:
- reacting a compound of formula
- with a compound of formula
- to give a compound of formula
- wherein
- A is phenyl or pyridin-2 or 3-yl;
- R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, lower alkyl, trifluoromethyl, S-lower alkyl, lower alkoxy, —OCHF2, phenyl, nitro, benzyloxy, hydroxy and amino, or alternatively, R1 and R2
- together with the carbon atoms to which they are attached from a group selected from —(CH2)3—, —O—CH2—O—, —CH2—O—CH2— and —CH2CH2—O—;
- R3 is selected from the group consisting of hydrogen, lower alkyl, phenyl, S-lower alkyl, amino, lower alkyl-amino, —NHC(O)-lower alkyl and hydroxy-lower alkyl;
- R4 and R5 are each independently selected from hydrogen and lower alkyl, or alternatively, R4 and R5 together with the carbon atom to which they are attached form the group —(CH2)4—;
- R6 and R6′ are each independently selected from hydrogen and lower alkyl;
- and
- hal is Br or Cl.
9 more elements
A process for preparing a compound of formula I comprising:
- cleaving off an N-protecting group from a compound of formula
- to give a compound of formula
- wherein
- R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, lower alkyl, cycloalkyl, lower alkenyl, trifluoromethyl, —O-trifluoromethyl, —S-trifluoromethyl, S-lower alkyl, lower alkoxy, —CHF2, —C(lower alkyl)F2, —OCHF2, phenyl, nitro, benzyloxy, hydroxy and amino, or alternatively, R1 and R2
- together with the carbon atoms to which they are attached in any adjacent positions from a group selected from —CH═CH—CH═CH—, —CH═CH—CH═N—, —(CH2)3—, —O—CH2—O—, —O—CF2—O—, —CH2—O—CH2— and —CH2CH2—O—;
- R3 is selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, phenyl, S-lower alkyl, amino, lower alkyl-amino, —NHC(O)-lower alkyl and hydroxy-lower alkyl;
- R4 and R5 are each independently selected from hydrogen and lower alkyl, or alternatively, R4 and R5 together with the carbon atom to which they are attached form the group —(CH2)4—;
- R6 and R6′ are each independently selected from hydrogen and lower alkyl;
- and
- P is an N-protecting group.
7 more elements
Dependencies are inferred from the claim text.