Imidazole derivatives

The compound of formula Ie in accordance with claim 16, which is selected from the group consisting of

• 3-(3,4-dimethyl-phenyl)-5-(2-methyl-imidazol-1-yl-methyl)-pyridine;
• 3-(4-fluoro-3-methyl-phenyl)-5-(2-methyl-imidazol-1-yl-methyl)-pyridine;
• 3-(4-chloro-3-methyl-phenyl)-5-(2-methyl-imidazol-1-yl-methyl)-pyridine;
• 3-(3-chloro-4-fluoro-phenyl)-5-(2-methyl-imidazol-1-yl-methyl)-pyridine;
• and
• 3-(4-chloro-3-trifluoromethyl-phenyl)-5-(2-methyl-imidazol-1-yl-methyl)-pyridine.

A compound of formula

• 43
• 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
• 44
• in formula I is selected from the group consisting of
• 45
• 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.

A compound selected from the group

• 3-(3-Difluoromethyl-4-fluoro-phenyl)-5-(2-methyl-imidazol-1-ylmethyl)-pyridine;
• 3-[3-(1,1-Difluoro-ethyl)-phenyl]-5-(2-methyl-imidazol-1-ylmethyl)-pyridine;
• 3-(3-Fluoro-5-trifluoromethyl-phenyl)-5-(2-methyl-imidazol-1-ylmethyl)-pyridine;
• 3-[3-(1,1-Difluoro-ethyl)-4-fluoro-phenyl]-5-(2-methyl-imidazol-1-ylmethyl)-pyridine;
• and
• 2-[5-(2-Methyl-imidazol-1-ylmethyl)-pyridin-3-yl]-1,2,3,4-tetrahydro-isoquinoline hydrochloride (1:2).

A method of making a compound of formula I comprising:

• reacting a compound of formula
• 46
• with a compound of formula
• 47
• to give a compound of formula
• 48
• wherein
• A is phenyl, pyridin-2 or 3-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 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
• hal is Cl or Br.

A method of making a compound of formula I comprising:

• reacting a compound of formula
• 49
• with a compound of formula
• 50
• to give a compound of formula
• 51
• wherein
• A is phenyl, pyridin-2 or 3-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 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 Cl or Br.

A method of making a compound of formula I comprising:

• reacting a compound of formula
• 52
• with a compound of formula
• 53
• to give a compound of formula
• 54
• wherein
• A is phenyl, pyridin-2 or 3-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 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 Cl or Br.