Benzofuran derivatives

Claim 2

A compound as claimed in Claim 1 or a physiologically acceptable salt, solvate or metabolically labile ester thereof wherein R¹ represents a hydrogen atom or a halogen atom or a group selected from C₁₋₆alkyl, C₂₋₆alkenyl, -CHO, -CO₂H or -COR²; Ar represents the group R² represents a group selected from C₁₋₆alkyl, C₂₋₆alkenyl, C₁₋₆alkoxy or the group -NR¹⁰R¹¹; R³ represents a group selected from -CO₂H, -NHSO₂CF₃ or a C-linked tetrazolyl group; R⁴ and R⁵, 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 a group selected from cyano, nitro, C₁₋₆alkyl, C₂₋₆alkenyl, perfluoroC₁₋₃alkyl, -(CH₂) m R⁶, -(CH₂) n COR⁷ or -(CH₂) p NR⁸COR⁹; R⁶ represents a hydroxy or C₁₋₆alkoxy group; R⁷ represents a hydrogen atom or a group selected from hydroxy, C₁₋₆alkyl, C₁₋₆alkoxy, phenyl, phenoxy or the group -NR¹⁰OR¹¹; R⁸ represents a hydrogen atom or a C₁₋₆alkyl group; R⁹ represents a hydrogen atom or a group selected from C₁₋₆alkyl, C₁₋₆alkoxy, phenyl, phenoxy or the group -NR₁₀R₁₁; R¹⁰ and R¹¹, which may be the same or different, each independently represent a hydrogen atom or a C₁₋₄alkyl group or -NR¹⁰R¹¹ 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.

Claim 3

A compound as claimed in Claim 1 or a physiologically acceptable salt, solvate or metabolically labile ester thereof wherein R¹ represents a hydrogen atom or a halogen atom or a group selected from C₁₋₆alkyl, C₂₋₆alkenyl, C₁₋₆alkoxy, -CHO, -CO₂H or -COR²; Ar represents the group R² represents a group selected from C₁₋₆alkyl, C₂₋₆alkenyl, C₁₋₆alkoxy or the group -NR¹⁰R¹¹; R³ represents a group selected from -CO₂H, -NHSO₂CF₃ or a C-linked tetrazolyl group; R⁴ and R⁵, 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 a group selected from cyano, nitro, C₁₋₆alkyl, C₂₋₆alkenyl, perfluoroC₁₋₃alkyl, -(CH₂) m R⁶, -(CH₂) n COR⁷ or -(CH₂) p NR⁸COR⁹; R⁶ represents a hydroxy or C₁₋₆alkoxy group; R⁷ represents a hydrogen atom or a group selected from hydroxy, C₁₋₆alkyl, C₁₋₆alkoxy, phenyl, phenoxy or the group -NR¹⁰R¹¹; R⁸ represents a hydrogen atom or a C₁₋₆alkyl group; R⁹ represents a hydrogen atom or a group selected from C₁₋₆alkyl, C₁₋₆alkoxy, phenyl, phenoxy or the group -NR¹⁰R¹¹; R¹⁰ and R¹¹, which may be the same or different, each independently represent a hydrogen atom or a C₁₋₄alkyl group or -NR¹⁰R¹¹ 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.

Claim 4

A compound as claimed in Claim 1 wherein Het represents an N-linked imidazolyl group substituted at the 2-position by a hydrogen atom or a C₁₋₅alkyl group, preferably an ethyl group, or by a C₃₋₅alkenyl group, preferably a but-1-enyl group.

Claim 5

A compound as claimed in any one of Claims 1 to 4 wherein Het represents an N-linked imidazolyl group substituted at the 2-position by a C₃₋₅alkyl group, for example an n-propyl or preferably an n-butyl group.

Claim 6

A compound as claimed in any one of Claims 1 to 5 wherein the N-linked imidazolyl group is substituted by one or two further substituents selected from a halogen atom or a group selected from C₁₋₆alkyl, -(CH₂) m R⁶ or -(CH₂) n COR⁷.

Claim 7

A compound as claimed in Claim 6 wherein the N-linked imidazolyl group is substituted by a halogen atom, preferably a chlorine atom.

Claim 8

A compound as claimed in Claim 6 or 7 wherein the N-linked imidazolyl group is substituted by a group selected from -(CH₂) m R⁶ wherein R⁶ is, for example, a C₁₋₆alkoxy group, such as a methoxy, ethoxy, propoxy or butoxy group, preferably a methoxy group, or R⁶ is preferably a hydroxy group, and m preferably represents 1 or 2; or -(CH₂) n COR⁷ wherein R⁷ is, for example, a hydrogen atom or a group selected from hydroxy, C₁₋₆alkoxy, for example a methoxy, ethoxy, propoxy or butoxy group, or the group -NR¹⁰R¹¹ where R¹⁰ and and R¹¹ each, for example, independently represents a hydrogen atom or a C₁₋₄alkyl group, R⁷ preferably representing a hydrogen atom, a hydroxy group or a methoxy group, and n preferably represents 0, 1 or 2.

Claim 9

A compound as claimed in Claim 8 wherein -(CH₂) m R⁶ is a group selected from -CH₂OH or -CH₂OCH₃; or -(CH₂) n COR⁷ is a group selected from -CHO, -CO₂H, -CO₂CH₂CH₃ or -CONH₂; or -(CH₂) n COR⁷ is a group selected from -CO₂CH₃ or -CONHCH₃.

Claim 10

A compound as claimed in any one of Claims 1 to 9 wherein the group Het-CH₂- is attached at the 5- or 6-position on the benzofuran ring, preferably the 5-position on the benzofuran ring.

Claim 11

A compound as claimed in any one of Claims 1 or 4 to 10 wherein R¹ represents a hydrogen atom or a halogen atom or a group selected from C₁₋₆alkyl, C₁₋₆alkoxy or fluoroC₁₋₆alkyl, such as a hydrogen atom or a halogen atom or a C₁₋₃alkyl group, preferably a halogen atom, more preferably a bromine atom.

Claim 12

A compound as claimed in any one of Claims 1 to 11 wherein R³ represents a -CO₂H group, or R³ represents a C-linked tetrazolyl group.

Claim 13

A compound as claimed in any one of Claims 1 to 12 wherein R⁴ and R⁵ each independently represents a hydrogen atom or a halogen atom, preferably R⁴ and R⁵ each independently represents a hydrogen atom.

Claim 14

A compound as claimed in Claim 1 of the general formula (I) or a physiologically acceptable salt, solvate or metabolically labile ester thereof wherein R¹ represents a hydrogen atom or a halogen atom or a group selected from C₁₋₆alkyl, C₁₋₆alkoxy or fluoroC₁₋₆alkyl; Ar represents the group R³ represents a group selected from -CO₂H, -NHSO₂CF₃ or a C-linked tetrazolyl group; R⁴ and R⁵ each independently represent a hydrogen atom or a halogen atom; Het represents an N-linked imidazolyl group optionally substituted at the 2-position by a C₁₋₆alkyl or C₂₋₆alkenyl group, the imidazolyl group optionally being substituted at the 4- and 5-positions by one or two further substituents selected from a halogen atom or a group selected from C₁₋₆alkyl, -(CH₂) m R⁶, -(CH₂) n COR⁷ or -(CH₂) p NR⁸COR⁹; R⁶ represents a hydroxy or a C₁₋₆alkoxy group; R⁷ represents a hydrogen atom or a group selected from hydroxy, C₁₋₆alkoxy or the group -NR¹⁰R¹¹ R⁸ represents a hydrogen atom; R⁹ represents a hydrogen atom or a group selected from C₁₋₆alkyl, C₁₋₆alkoxy or the group -NR¹⁰R¹¹; R¹⁰ and R¹¹ each independently represent a hydrogen atom or a C₁₋₄alkyl group or -NR¹⁰R¹¹ forms a pyrrolidino heterocyclic ring; m represents an integer from 1 or 4; n represents an integer from 0 to 4; and p represents an integer from 1 to 4.

Claim 15

A compound as claimed in Claim 1 selected from: 5-[2-[3-bromo-5-[[2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl]methyl]-2-benzofuranyl]phenyl]tetrazole; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazole-5-carboxaldehyde; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazole-5-carboxylic acid; 5-[2-[3-bromo-5-[(2-butyl-1H-imidazol-1-yl)methyl]-2-benzofuranyl]phenyl]-1H-tetrazole; 2-[3-bromo-5-[2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl]-2-benzofuranyl]benzoic acid; 5-[2-[5-[[2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl]methyl]-3-methyl-2-benzofuranyl]phenyl]-1H-tetrazole; ethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazole-5-carboxylate; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-but-1(E)-enyl-4-chloro-1H-imidazole-5-carboxylic acid; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-chloro-2-propyl-1H-imidazole-5-carboxylic acid; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-1H-imidazole-4,5-dicarboxylic acid; 5-[2-[3-bromo-5-[[2-butyl-4-chloro-5-(methoxymethyl)-1H-imidazol-1-yl]methyl]-2-benzofuranyl]phenyl]-1H-tetrazole; 2-butyl-4-chloro-1-[[2-[(1H-tetrazol-5-yl)phenyl]-3-(trifluoromethyl)-5-benzofuranyl]methyl]-1H-imidazole-5-carboxylic acid; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]benzofuran-5-yl]methyl]-2-butyl-4-chloro-1H-imidazole-5-carboxylic acid, (acetyloxy)methyl ester; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]benzofuran-5-yl]methyl]-2-butyl-4-chloro-1H-imidazole-5-carboxylic acid, 1-(acetyloxy)ethyl ester; 1-(ethoxycarbonyloxy)ethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazole-5-carboxylate; 2-methoxyethyl- 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazole-5-carboxylate; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]- 2-butyl-4-chloro-1H-imidazole-5-carboxamide; 1-[[l-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl-2-butyl-4-chloro-1H-imidazol-5-yl]carbonyl]pyrrolidine; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-N-methyl-1H-imidazole-5-carboxamide; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-N,N-dimethyl-1H-imidazole-5-carboxamide; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-N-ethyl-1H-imidazole-5-carboxamide; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-chloro-2-ethyl-1H-imidazole-5-carboxylic acid; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-1H-imidazole-5-carboxylic acid; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)-phenyl]-5-benzofuranyl]methyl]-4-chloro-2-propyl-N-methyl-1H-imidazole-5-carboxamide; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-N-isopropyl-1H-imidazole-5-carboxamide; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-iodo-1H-imidazole-5-carboxylic acid; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-trifluoromethyl-1H-imidazole-5-carboxylic acid; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-methyl-1H-imidazole-5-carboxylic acid, hydrochloride (1:1); 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazole-5-acetic acid; ethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazole-5-acetate; 1-[[3-bromo-2-[2-(ethoxycarbonyl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazole-5-carboxylic acid; 1-[[3-bromo-2-(2-carboxyphenyl)-5-benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazole-5-carboxylic acid; methyl [[1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazol-5-yl]methyl]carbamate; 1-[5-[3-chloro-2-[2-(1H-tetrazol-5-yl)phenyl]benzofuranyl]methyl]-2-butyl-4 -chloro-1H-imidazole-5-carboxylic acid; 1-[[3-methoxy-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazole-5-carboxylic acid; 2-methoxy-1-methylethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazole-5-carboxylate; 1-[[3-bromo-2-[2-[[(trifluoromethyl)sulphonyl]amino]phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazole-5-carboxylic acid. 3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazole-5-carboxylic acid, dipotassium salt; ethyl 1-[[3-bromo-2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-chloro-2-ethyl-1H-imidazole-5-carboxylate; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-chloro-2-ethyl-N-isopropyl-1H-imidazole-5carboxamide; ethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-chloro-2-propyl-1H-imidazole-5carboxylate; ethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-methyl-2-propyl-1H-imidazole-5carboxylate; ethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-methyl-1H-imidazole-5-carboxylate; ethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-5-methyl-1H-imidazole-4-carboxylate; ethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-chloro-2-methyl-1H-imidazole-5carboxylate; ethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-ethyl-4-methyl-1H-imidazole-5-carboxylate hydrochloride; 1-[[3-bromo-2-[2-(1H-tetrazo1-5-yl)phenyl]-5-benzofuranyl]methyl]-2-ethyl-4-methyl-N-methyl-1H-imidazole-5-carboxamide hydrochloride; butyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-chloro-2-ethyl-1H-imidazole-5-carboxylate; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-methyl-2-propyl-1H-imidazole-5-carboxylic acid; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-methyl-1H-imidazole-5-carboxylic acid; ethyl 1-[5-[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]benzofuranyl]methyl]-2-butyl-4-methyl-1H-imidazole-5-carboxylate; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-chloro-2-methyl-1H-imidazole-5-carboxylic acid; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-ethyl-4-methyl-1H-imidazole-5-carboxylic acid hydrochloride; ethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-methyl-2-pentyl-1H-imidazole-5-carboxylate; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-methyl-2-pentyl-1H-imidazole-5-carboxylic acid; ethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2,4-dimethyl-1H-imidazole-5-carboxylate; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2,4-dimethyl-1H-imidazole-5-carboxylic acid; ethyl 1-[[3-bromo-2-[2-[[(trifluoromethyl)sulphonyl]amino]phenyl]-5-benzofuranyl]methyl]-4-methyl-2-propyl-1H-imidazole-5-carboxylate; 1-[[3-bromo-2-[2[[(trifluoromethyl)sulphonyl]amino]phenyl]-5-benzofuranyl]methyl]-4-methyl-2-propyl-1H-imidazole-5-carboxylyic acid; 1-[[3-bromo-2-[2[[(trifluoromethyl)sulphonyl]amino]phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-N-methyl-1H-imidazole-5-carboxamide; and physiologically acceptable salts, solvates and metabolically labile esters thereof.

Claim 16

A process for the preparation of a compound as claimed in any one of Claims 1 to 15 or a physiologically acceptable salt, solvate or metabolically labile ester thereof which comprises: (A) reacting a benzofuran of general formula (II) in which L represents a leaving group, with an imidazole of general formula (III) in which R¹² represents a hydrogen atom or a group selected from C₁₋₆alkyl, C₂₋₆alkenyl or C₁₋₆alkylthio and R¹³ and R¹⁴ each independently represent a hydrogen atom or a halogen atom or a group selected from cyano, nitro, C₁₋₆alkyl, C₂₋₆alkenyl, fluoroC₁₋₆alkyl, -(CH₂) m R⁶, -(CH₂) n COR⁷, -(CH₂) p NR⁸COR⁹, followed, if necessary, by removal of any protecting group present; or (B) deprotecting a protected intermediate of general formula (IV) in which at least one reactive group is blocked by a protecting group; (C) reacting a compound of general formula (Ia) in which R³ in the group Ar 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 R³ in the group Ar represents an amino group, to a compound of general formula (I) in which R³ 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, solvate or metabolically labile ester thereof.

Claim 17

A process as claimed in Claim 16 which comprises: (A) reacting a benzofuran of general formula (II) in which L represents a leaving group, with an imidazole of general formula (III) in which R¹² represents a hydrogen atom or a group selected from C₁₋₆alkyl, C₂₋₆alkenyl or C₁₋₆alkylthio and R¹³ and R¹⁴ each independently represent a hydrogen atom or a halogen atom or a group selected from cyano, nitro, C₁₋₆alkyl, C₂₋₆alkenyl, fluoroC₁₋₆alkyl, -(CH₂) m R⁶, -(CH₂) n COR⁷, -(CH₂) p NR⁸COR⁹, followed, if necessary by removal of any protecting group present; or (B) deprotecting a protected intermediate of general formula (IV) in which at least one reactive group is blocked by a protecting group; or (C) reacting a compound of general formula (Ia) in which R³ in the group Ar represents a nitrile group, with an azide, followed, if necessary by the removal of any protecting group present; 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, solvate or metabolically labile ester thereof.

Claim 18

A pharmaceutical composition comprising at least one compound of general formula (I) as defined in any one of Claims 1 to 15 or a physiologically acceptable salt, solvate or metabolically labile ester thereof, together with at least one physiologically acceptable carrier or excipient.

Claim 19

A compound of general formula (I) as claimed in any one of Claims 1 to 15 or a physiologically acceptable salt, solvate or metabolically labile ester thereof for use in therapy, for example (i) for use in the treatment or prophylaxis of hypertension; or (ii) for use in the treatment or prophylaxis of a disease associated with cognitive disorders, renal failure, hyperaldosteronism, cardiac insufficiency, congestive heart failure, post-myocardial infarction, cerebrovascular disorders, glaucoma and disorders of intracellular homeostasis; or (iii) for use in the treatment of conditions associated with excessive or unregulated angiotensin II activity.

Claim 20

A compound of general formula (II) or an acid addition salt thereof wherein R¹ and Ar are as defined in Claim 1; and L represents a leaving group.

Claim 21

A compound of general formula (Ia) or an acid addition salt thereof wherein R¹, Ar and Het are as defined in Claim 1 except that in the group Ar, R³ represents a nitrile group.

Claim 22

A compound of general formula (Ib) or an acid addition salt thereof wherein R¹, Ar and Het are as defined in Claim 1 except that in the group Ar, R³ represents an amino group.

Claim 23

A compound selected from:- 1-[[3-bromo-2-(2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazole-5-carboxylic acid; ethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl4-chloro-1H-imidazole-5-carboxylate; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-chloro-2propyl-1H-imidazole-5-carboxylic acid; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-N-methyl-1H-imidazole-5-carboxamide; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl-5-benzofuranyl]methyl]-2-butyl-4-chloro-N-ethyl-1H-imidazole-5-carboxamide; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-chloro-2-ethyl-1H-imidazole-5-carboxylic acid; 1-[[5-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-1-benzofuranyl]methyl]-2-butyl-4methyl-1H-imidazole-5-carboxylic acid, hydrochloride (1: 1); 1-[[3-bromo-2-(2-carboxyphenyl)-5-benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazole-5-carboxylic acid 1-[5-[3-chloro-2-[2-(1H-tetrazol-5-yl)phenyl]benzofuranyl]methyl]-2-butyl-4-chloro-1H-imidazole-5-carboxylic acid; 1-[[3-bromo-2-[2-[[(trifluoromethyl)sulphonyl]amino]phenyl]-5-benzofuranyl]methyl]-2-butyl4-chloro-1H-imidazole-5-carboxylic acid; ethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-chloro-2-ethyl-1H-imidazole-5-carboxylate; ethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-chloro-2-propyl-1H-imidazole-5-carboxylate; ethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-methyl-2-propyl-1H-imidazole-5-carboxylate; ethyl 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-butyl-4-methyl-1H-imidazole-5-carboxylate; ethyl 1-[[3-bromo2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-ethyl-4-methyl-1H-imidazole-5-carboxylate hydrochloride; 1-[[3-bromo-2-[2-[1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-4-methyl-2-propyl-1H-imidazole-5-carboxylic acid; ethyl 1-[5-[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]benzofuranyl]methyl]-2-butyl-4-methyl-1H-imidazole-5-carboxylate; 1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzofuranyl]methyl]-2-ethyl-4-methyl-1H-imidazole-5-carboxylic acid hydrochloride; 1-[[3-bromo-2-[2-[[(trfluoromethyl)sulphonyl]amino]phenyl]-5-benzofuranyl]methyl]-4-methyl-2-propyl-1H-imidazole-5-carboxylic acid; 1-[[3-bromo-2-[2-[[(trifluoromethyl)sulphonyl]amino]phenyl]-5-benzofuranyl]methyl]-2-butyl-4-chloro-N-methyl-1H-imidazole-5-carboxamide; and physiologically acceptable salts, solvates and metabolically labile esters thereof.