Indole derivatives

Claim 1

A process for the preparation of a compound of the general formula (I) or a physiologically acceptable salt or solvate thereof wherein R¹ represents a hydrogen atom or a halogen atom or a group selected from C₁₋₆alkyl, C₂₋₆alkenyl, fluoroC₁₋₆alkyl, -CHO, -CO₂H or -COR⁴; R² represents a hydrogen atom or a halogen atom or the group Ar; R³ represents a hydrogen atom or a group selected from C₁₋₆alkyl, C₃₋₆alkenyl, C₁₋₆alkoxy, -COR⁴, -SO₂R⁴ or the group Ar; R⁴ represents a group selected from C₁₋₆alkyl, C₂₋₆alkenyl, C₁₋₆alkoxy or the, group -NR¹²R¹³; Ar represents the group R⁵ represents a group selected from -CO₂H, -NHSO₂CF₃ or a C-linked tetrazolyl group; R⁶ and R⁷, which may be the same or different, each independently represent a hydrogen atom or a halogen atom or a C₁₋₆alkyl group; Het represents an N-linked imidazolyl group substituted at the 2-position by a C₁₋₆alkyl, C₂₋₆alkenyl or a C₁₋₆alkylthio group, the imidazolyl group optionally being substituted by one or two further substituents selected from a halogen atom or group selected from cyano, nitro, C₁₋₆alkyl, C₂₋₆alkenyl, fluoroC₁₋₆alkyl, -(CH₂) m R⁸, -(CH₂) n COR⁹ or -(CH₂) p NR¹⁰COR¹¹; or Het represents an N-linked benzimidazolyl group substituted at the 2-position by a C₁₋₆alkyl, C₂₋₆alkenyl or a C₁₋₆alkylthio group; R⁸ represents a hydroxy or C₁₋₆alkoxy group; R⁹ represents a hydrogen atom or a group selected from hydroxy, C₁₋₆alkyl, C₁₋₆alkoxy, phenyl, phenoxy or the group -NR¹²R¹³; R¹⁰ represents a hydrogen atom or a C₁₋₆alkyl group; R¹¹ represents a hydrogen atom or a group selected from C₁₋₆alkyl, C₁₋₆alkoxy, phenyl, phenoxy or the group -NR¹²R¹³; R¹² and R¹³, which may be the same or different, each independently represent a hydrogen atom or a C₁₋₄alkyl group or -NR¹²R¹³ forms a saturated heterocyclic ring which has 5 or 6 ring members and may optionally contain in the ring one oxygen atom; m represents an integer from 1 to 4; n represents an integer from 0 to 4; and p represents an integer from 1 to 4; provided that one of R² and R³ represents the group Ar, and that when R² represents the group Ar, R³ represents a hydrogen atom or a group selected from C₁₋₆alkyl, C₃₋₆alkenyl, C₁₋₆alkoxy, -COR⁴ or -SO₂R⁴, and that when R³ represents the group Ar, R² represents a hydrogen atom or a halogen atom; which comprises: (A) reacting an indole of general formula (II) in which L is a leaving group, with an imidazole of formula (III) in which R¹⁴ represents a group selected from C₁₋₆alkyl, C₂₋₆alkenyl or C₁₋₆alkylthio and R¹⁵ and R¹⁶ each independently represent a hydrogen or halogen atom or a group selected from cyano, nitro, C₁₋₆alkyl, C₂₋₆alkenyl, fluoroC₁₋₆alkyl, -(CH₂) m R⁸, -(CH₂) n COR⁹, -(CH₂) p NR¹⁰COR¹¹ or when taken together with the carbon atoms to which R¹⁵ and R¹⁶ are attached, there is formed a fused phenyl ring, followed, if necessary, by removal of any protecting group present; or (B) deprotecting a protected intermediate of general formula (IV) in which R 3a is a protecting group and/or at least one reactive group is blocked by a protecting group; or (C) reacting a compound of general formula (Ia) in which R⁵ in the group Ar as the substituent R² or R³ represents a nitrile group, with an azide, followed, if necessary, by the removal of any protecting group present; or (D) converting a compound of general formula (Ib) in which R⁵ in the group Ar as the substituent R² or R³ represents an amino group, to a compound of general formula (I) in which R⁵ represents -NHSO₂CF₃; and when the compound of formula (I) is obtained as a mixture of enantiomers optionally resolving the mixture to obtain the desired enantiomer; and/or, if desired, converting the resulting compounds of general formula (I) or a salt thereof into a physiologically acceptable salt or solvate thereof.