Benzthiophen derivatives

Claim 2

A compound of the general formula (I) or a physiologically acceptable salt, solvate or metabolically labile ester thereof wherein R 1 represents a hydrogen atom or a halogen atom or a group selected from C 1-6 alkyl, C 2-6 alkenyl, fluo- roC 1-6 alkyl, C 1-6 alkoxy, -CHO, -C0 2 H or-COR2 ; Ar represents the group R 2 represents a group selected from C 1-6 alkyl, C 2-6 alkenyl,C 1-6 alkoxy or the group ―NR 10 R 11 ; R 3 represents a group selected from -C0 2 H, -NHSO 2 CF 3 or a C-linked tetrazolyl group ; R 4 and R 5 , which may be the same or different, each independently represent a hydrogen atom or a halogen atom or a C 1-6 alkyl group ; Het represents an N-linked imidazolyl group optionally substituted at the 2-position by a C 1-6 alkyl, C 2-6 alkenyl or a C 1-6 alkylthio 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 cyano, nitro, C 1- 6 alkyl, C 2-6 alkenyl, fluoroC 1-6 alkyl, ―(CH 2 ) m R 6 , ―(CH 2 ) n COR 7 or ―(CH 2 )pNR 8 COR 9 ; R 6 represents a hydroxy or C 1-6 alkoxy group ; R 7 represents a hydrogen atom or a group selected from hydroxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, phenoxy or the group ―NR 10 R 11 ; R 8 represents a hydrogen atom or a C 1-6 alkyl group ; R 9 represents a hydrogen atom ora group selected from C 1-6 alkyl, C 1-6 alkoxy, phenyl, phenoxy or the group ―NR 10 R 11 ; R 10 and R 11 , which may be the same or different, each independently represent a hydrogen atom or a C 1- 4 alkyl group or ―NR 10 R 11 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 R 1 represents a hydrogen atom or a halogen atom or a group selected from C 1-6 alkyl, C 2-6 alkenyl,―CHO, ―CO 2 H or ―COR 2 ; Ar represents the group R 2 represents a group selected from C 1-6 alkyl, C2-6alkenyl, C 1-6 alkoxy or the group ―NR 10 R 11 ; R 3 represents a group selected from ―CO 2 H,―NHSO 2 CF 3 or a C-linked tetrazolyl group ; R 4 and R 5 , which may be the same or different, each independently represent a hydrogen atom or a halogen atom or a C 1-6 alkyl group ; Het represents an N-linked imidazolyl group substituted at the 2-position by a C 1-6 alkyl, C 2-6 alkenyl or a C 1-6 alkylthio group, the imidazolyl group optionnally being substituted by one or two further substituents selected from a halogen atom or a group selected from cyano, nitro, C 1-6 alkyl, C 2 - 6 alkenyl, perfluoroC 1- 3alkyl, ―(CH 2 ) m R 6 , ―(CH 2 ) n COR 7 or ―(CH 2 ) p NR 8 COR 9 ; R 6 represents a hydroxy or C 1-6 alkoxy group ; R 7 represents a hydrogen atom or a group selected from hydroxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, phenoxy or the group ―NR 10 R 11 ; R 8 represents a hydrogen atom or a C 1-6 alkyl group ; R 9 represents a hydrogen atom or a group selected from C 1-6 alkyl,C 1-6 alkoxy, phenyl, phenoxy or the group ―NR 10 R 11 ; R 10 and R", which may be the same or different, each independently represent a hydrogen atom or a C 1-4 alkyl group or ―NR 10 R 11 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 or a physiologically acceptable salt, solvate or metabolically labile ester thereof wherein R 1 represents a hydrogen atom or a halogen atom or a group selected from C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, ―CHO, ―CO 2 H or ―COR 2 ; Ar represents the group R 2 represents a group selected from C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy or the group ―NR 10 R 11 ; R 3 represents a group selected from ―CO 2 H, ―NHSO 2 CF 3 or a C-linked tetrazolyl group ; R 4 and R 5 , which may be the same or different, each independently represent a hydrogen atom or a halogen atom or a C 1-6 alkyl group ; Het represents an N-linked imidazolyl group substituted at the 2-position by a C 1-6 alkyl, C 2 - 6 alkenyl or a C 1-6 alkylthio 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, C 1-6 alkyl, C 2-6 alkenyl, perfluoroC 1- 3alkyl,―(CH 2 ) m R 6 , ―(CH 2 ) n COR 7 or ―(CH 2 ) p NR 8 COR 9 ; R 6 represents a hydroxy or C 1-6 alkoxy group ; R 7 represents a hydrogen atom or a group selected from hydroxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, phenoxy or the group ―NR 10 R 11 ; R 8 represents a hydrogen atom or a C 1-6 alkyl group ; R 9 represents a hydrogen atom ora group selected from C 1-6 alkyl, C 1-6 alkoxy, phenyl, phenoxy or the group ―NR 10 R 11 ; R 10 and R 11 , which may be the same or different, each independently represent a hydrogen atom or a C 1- 4 alkyl group or ―NR 10 R 11 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 5

A compound as claimed in Claim 1 wherein Het is an N-linked imidazolyl group substituted at the 2-position by a hydrogen atom or a C 1-5 alkyl or a C 3-5 alkenyl group, preferably a C 3-5 alkyl group, for example an n-butyl group, and the N-linked imidazolyl group is substituted at the 4- and 5- positions by one or two further substituents selected from a halogen atom, preferably a chlorine atom, or a group selected from C 1-6 alkyl, ―(CH 2 ) m R 6 or ―(CH 2 ) n COR 7 ,especially ―(CH 2 ) n COR 7 , in which R 7 is a hydroxy group and n is 0, 1 or 2.

Claim 6

A compound as claimed in Claim 4 wherein the N-linked imidazolyl group is substituted at the 4-or 5- position by a-C02H group.

Claim 7

A compound as claimed in any one of in Claims 1 to 5 wherein the group Het-CH 2 ― is attached at the 5- position on the benzthiophen ring.

Claim 8

A compound as claimed in any one of Claims 1 and 4 to 6 wherein R 1 represents a hydrogen atom or a halogen atom or a group selected from C 1-6 alkyl, C 1-6 alkoxy or fluoroC 1-6 alkyl, preferably a hydrogen atom or a bromine atom.

Claim 9

A compound as claimed in any one of Claims 1 to 7 wherein R 3 represents a C-linked tertazolyl group.

Claim 10

A compound as claimed in any one of Claims 1 to 8 wherein R 4 and R 5 each independently represents a hydrogen atom.

Claim 11

A compound as claimed in Claim 1 or a physiologically acceptable salt, solvate or metabolically labile ester thereof wherein R 1 represents a hydrogen atom or a halogen atom ; Ar represents the group R 3 represents a C-linked tetrazolyl group ; R 4 and R 5 each independently represent a hydrogen atom ; Hetrepresents an N-linked imidazolyl group substituted at the 2-position by a C 1-6 alkyl group, the imidazolyl group being substituted at the 4- and 5-positions by two further substituents selected from a halogen atom or a―(CH 2 ) n COR 7 group ; R 7 represents a hydroxy group ; and n represents an integer from 0 to 4.

Claim 12

A compound as claimed in Claim 1 selected from : 1-[[3-bromo-2-(2-(1H-tetrazol-5-yl)phenyl]-5-benzo-[b]thiophenyl]methyl]-2-butyl-4-chloro-1H-imidazo le-5-carboxylic acid ; 1-[2-[2-(1 H-tetrazol-5-yl)phenyl]-5-benzo[b]thiophenyl]methyl]-2-butyl-4-chloro-1 H-imidazole-5-carb oxylic acid ; and physiologically acceptable salts, solvates and metabolically labile esters thereof.

Claim 13

A process for the preparation of a compound as claimed in any one of Claims 1 to 11 or a physiologically acceptable salt, solvate or metabolically labile ester thereof which comprises : (A) reacting a benzthiophen of general formula (II) in which L represents a leaving group, with an imidazole of general formula (III) in which R 12 represents a hydrogen atom or a group selected from C 1-6 alkyl, C 2-6 alkenyl or C 1-6 alkylthio and R 13 and R 14 each independently represent a hydrogen atom or a halogen atom or a group selected from cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, fluoroC 1-6 alkyl, ―(CH 2 ) m R 6 , ―(CH 2 ) n COR 7 , ―(CH 2 ) p NR 8 COR 9 , 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 (la) in which R 3 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 R 3 in the group Ar represents an amino group, to a compound of general formula (I) in which R 3 represents -NHS0 2 CF 3 ; 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 14

A process as claimed in Claim 12 which comprises: (A) reacting a benzthiophen of general formula (II) in which L represents a leaving group, with an imidazole of general formula (III) in which R 12 represents a hydrogen atom or a group selected from C 1-6 alkyl, C 2 - 6 alkenyl or C 1-6 alkylthio and R 13 and R 14 each independently represent a hydrogen atom or a halogen atom or a group selected from cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, fluoroC 1-6 alkyl, ―(CH 2 ) m R 6 , ―(CH 2 ) n COR 7 , -(CH 2 ) p NR 8 COR 9 , 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 (la) in which R 3 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 15

A pharmaceutical composition comprising at least one compound of general formula (I) as defined in any one of claims 1 to 11 or a physiologically acceptable salt, solvate or metabolically labile ester thereof, together with at least one physiologically acceptable carrier or excipient.

Claim 16

A compound of general formula (I) as claimed in any one of Claims 1 to 11 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 the 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 17

A compound of general formula (11) or an acid addition salt thereof wherein R 1 and Ar are as defined in Claim 1 ; and L represents a leaving group.

Claim 18

A compound of general formula (la) or an acid addition salt thereof wherein R l , Ar and Het are as defined in Claim 1 except that in the group Ar, R 3 represents a nitrile group.

Claim 19

A compound of general formula (Ib) or an acid addition salt thereof wherein R 1 , Ar and Het are as defined in Claim 1 except that in the group Ar, R 3 represents an amino group. Claims for the following Contracting States : ES & GR

Claim 20

A process for the preparation of a compound of the general formula (I) or a physiologically acceptable salt, solvate or metabolically labile ester thereof wherein R 1 represents a hydrogen atom or a halogen atom or a group selected from C 1 - 6 alkyl, C 2-6 alkenyl, fluo- roC 1-6 alkyl, C 1-6 alkoxy,―CHO,―CO 2 H or ―COR 2 ; Ar represents the group R 2 represents a group selected from C 1-6 alkyl, C 2-6 alkenyl. C 1-6 alkoxy or the group ―NR 10 R 11 ; R 3 represents a group selected from ―CO 2 H,―NHSO 2 CF 3 or a C-linked tetrazolyl group ; R 4 and R 5 , which may be the same or different, each independently represent a hydrogen atom or a halogen atom or a C 1-6 alkyl group; Het represents an N-linked imidazolyl group optionally substituted at the 2-position by a C 1-6 alkyl, C 2-6 alkenyl, or a C 1-6 alkylthio 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 cyano, nitro, C 1- 6 alkyl, C 2 - 6 alkenyl, fluoroC 1-6 alkyl, ―(CH 2 ) m R 6 , ―(CH 2 ) n COR 7 or ―(CH 2 ) p NR 8 COR 9 ; R 6 represents a hydroxy or C 1-6 alkoxy group ; R 7 represents a hydrogen atom or a group selected from hydroxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, phenoxy or the group ―NR 10 R 11 ; R 8 represents a hydrogen atom or a C 1-6 alkyl group ; R 9 represents a hydrogen atom ora group selected from C 1-6 alkyl, C 1-6 alkoxy, phenyl, phenoxy or the group ―NR 10 R 11 ; R 10 and R 11 , which may be the same or different, each independently represent a hydrogen atom or a C 1- 4 alkyl group or ―NR 10 R 11 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 ; which comprises: (A) reacting a benzthiophen of general formula (11) in which L represents a leaving group, with an imidazole of general formula (III) in which R 12 represents a hydrogen atom or a group selected from C 1-6 alkyl, C 2-6 alkenyl or C 1-6 alkylthio and R 13 and R 14 each independently represent a hydrogen atom or a halogen atom or a group selected from cyano, nitro, C 1-6 alkyl, C 24 alkenyl, fluoroC 1-6 alkyl, ―(CH 2 ) m R 6 , ―(CH 2 ) n COR 7 , ―(CH 2 ) p NR 8 COR 9 , 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 R 3 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 R 3 in the group Ar represents an amino group, to a compound of general formula (I) in which R 3 represents ―NHSO 2 CF 3 ; 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 on metabolically labile ester thereof.

Claim 21

A process for the preparation of a compound of the general formula (I) or a physiologically acceptable salt, solvate or metabolically labile ester thereof wherein R 1 represents a hydrogen atom or a halogen atom or a group selected from C 1 - 6 alkyl, C 2-6 alkenyl, fluo- roC 1-6 alkyl, C 1-6 alkoxy,―CHO,―CO 2 H or ―COR 2 ; Ar represents the group R 2 represents a group selected from C 1-6 alkyl, C 2-6 alkenyl. C 1-6 alkoxy or the group ―NR 10 R 11 ; R 3 represents a group selected from ―CO 2 H,―NHSO 2 CF 3 or a C-linked tetrazolyl group ; R 4 and R 5 , which may be the same or different, each independently represent a hydrogen atom or a halogen atom or a C 1-6 alkyl group; Het represents an N-linked imidazolyl group optionally substituted at the 2-position by a C 1-6 alkyl, C 2-6 alkenyl, or a C 1-6 alkylthio 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 cyano, nitro, C 1- 6 alkyl, C 2 - 6 alkenyl, fluoroC 1-6 alkyl, ―(CH 2 ) m R 6 , ―(CH 2 ) n COR 7 or ―(CH 2 ) p NR 8 COR 9 ; R 6 represents a hydroxy or C 1-6 alkoxy group ; R 7 represents a hydrogen atom or a group selected from hydroxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, phenoxy or the group ―NR 10 R 11 ; R 8 represents a hydrogen atom or a C 1-6 alkyl group ; R 9 represents a hydrogen atom ora group selected from C 1-6 alkyl, C 1-6 alkoxy, phenyl, phenoxy or the group ―NR 10 R 11 ; R 10 and R 11 , which may be the same or different, each independently represent a hydrogen atom or a C 1- 4 alkyl group or ―NR 10 R 11 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 ; which comprises: (A) reacting a benzthiophen of general formula (11) in which L represents a leaving group, with an imidazole of general formula (III) in which R 12 represents a hydrogen atom or a group selected from C 1-6 alkyl, C 2-6 alkenyl or C 1-6 alkylthio and R 13 and R 14 each independently represent a hydrogen atom or a halogen atom or a group selected from cyano, nitro, C 1-6 alkyl, C 24 alkenyl, fluoroC 1-6 alkyl, ―(CH 2 ) m R 6 , ―(CH 2 ) n COR 7 , ―(CH 2 ) p NR 8 COR 9 , 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 R 3 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 R 3 in the group Ar represents an amino group, to a compound of general formula (I) in which R 3 represents ―NHSO 2 CF 3 ; 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 on metabolically labile ester thereof.

Claim 22

A process for the preparation of a compound of general formula (I) as defined in Claim 1 or a physiologically acceptable salt, solvate or metabolically labile ester thereof which comprises: (A) reacting a benzthiophen of general formula (II) in which L represents a leaving group, with an imidazole of general formula (III) in which R 12 represents a hydrogen atom or a group selected from C 1-6 alkyl, C 2-6 alkenyl or C 1-6 alkylthio and R13 and R1 4 each independently represent a hydrogen atom or a halogen atom or a group selected from cyano, nitro, C 1-6 alkyl, C2-6alkenyl, fluoroC 1-6 alkyl, ―(CH 2 ) m R 6 , ―(CH 2 ) n COR 7 , ―(CH 2 ) p NR 8 COR 9 , 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 R 3 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 23

A process as claimed in Claim 1 or 2 for the preparation of a compound of the general formula (1) or a physiologically acceptable salt, solvate or metabolically labile ester thereof wherein R 1 represents a hydrogen atom or a halogen atom or a group selected from C 1-6 alkyl, C 2-6 alkenyl, ―CHO, ―CO 2 H or ―COR 2 ; Ar represents the group R 2 represents a group selected from C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy or the group ―NR 10 R 11 ; R 3 represents a group selected from ―CO 2 H, -NHS0 2 CF 3 or a C-linked tetrazolyl group ; R 4 and R 5 , which may be the same or different, each independently represent a hydrogen atom or a halogen atom or a C 1-6 alkyl group ; Het represents an N-linked imidazolyl group substituted at the 2-position by a C 1-6 alkyl, C 2-6 alkenyl, or a C 1-6 alkylthio 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, C 1-6 alkyl, C 2-6 alkenyl, perfluoroC 1- 3 alkyl, ―(CH 2 ) m R 6 , ―(CH 2 ) n COR 7 or ―(CH 2 ) p NR 8 COR 9 ; R 6 represents a hydroxy or C 1-6 alkoxy group ; R 7 represents a hydrogen atom or a group selected from hydroxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, phenoxy or the group ―NR 10 R 11 ; R 8 represents a hydrogen atom or a C 1-6 alkyl group ; R 9 represents a hydrogen atom or a group selected from C 1-6 alkyl, C 1-6 alkoxy, phenyl, phenoxy or the group ―NR 10 R 11 ; R 10 and R 11 which may be the same or different, each independently represent a hydrogen atom or a C 1- 4 alkyl group or ―NR 10 R 11 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 24

A process as claimed in Claim 1 or 2 for the preparation of a compound of the general formula (I) or a physiologically acceptable salt, solvate or metabolically labile ester thereof wherein R 1 represents a hydrogen atom or a halogen atom or a group selected from C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, ―CHO, ―CO 2 H or ―COR 2 ; Ar represents the group R 2 represents a group selected from C 1-6 alkyl, C 24 alkenyl, C 1-6 alkoxy or the group ―NR 10 R 11 ; R 3 represent a group selected from -C0 2 H, -NHS0 2 CF 3 or a C-linked tetrazolyl group ; R 4 and R 5 , which may be the same or different, each independently represent a hydrogen atom or a halogen atom or a C 1-6 alkyl group ; Het represents an N-linked imidazolyl group substituted at the 2-position by a C 1-6 alkyl, C 2-6 alkenyl or a C 1-6 alkylthio 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, C 1-6 alkyl, C 2-6 alkenyl, perfluoroC 1- 3alkyl,―(CH 2 ) m R 6 , ―(CH 2 ) n COR 7 or ―(CH 2 ) p NR 8 COR 9 ; R 6 represents a hydroxy or C 1-6 alkoxy group; R 7 represents a hydrogen atom or a group selected from hydroxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, phenoxy or the group ―NR 10 R 11 ; R 8 represents a hydrogen atom or a C 1-6 alkyl group ; R 9 represents a hydrogen atom ora group selected from C 1-6 alkyl, C 1-6 alkoxy, phenyl, phenoxy or the group ―NR 10 R 11 ; R 10 and R 11 , which may be the same or different, each independently represent a hydrogen atom or a C 1- 4 alkyl group or ―NR 10 R 11 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 25

A process as claimed in any one of Claims 1 to 4 for the preparation of a compound wherein Het is an N-linked imidazolyl group substituted at the 2-position by a hydrogen atom or a C 1-5 alkyl or a C 3-5 alkenyl group, preferably C 3-5 alkyl group, for example an n-butyl group, and the N-linked imidazolyl group is substituted atthe 4- and 5- positions by one ortwo further substituents selected from a halogen atom, preferably a chlorine atom, or a group selected from C 1-6 alkyl, ―(CH 2 ) m R 6 or ―(CH 2 ) n COR 7 , especially ―(CH 2 ) n COR 7 , in which R 7 is a hydroxy group and n is 0, 1 or 2.

Claim 26

A process as claimed in Claim 5 for the preparation of a compound wherein the N-linked imidazolyl group is substituted by a -C0 2 H group.

Claim 27

A process as claimed in any one of Claims 1 to 6 for the preparation of a compound wherein the group Het-CH 2 ― is attached at the 5- position on the benzthiophen ring.

Claim 28

A process as claimed in any one of Claims 1 and 4 to 7 for the preparation of a compound wherein R i represents a hydrogen atom or a halogen atom or a group selected from C 1-6 alkyl, C 1-6 alkoxy or fluoroC 1-6 alkyl, preferably a hydrogen atom or a bromine atom.

Claim 29

A process as claimed in any one of Claims 1 to 8 for the preparation of a compound wherein R 3 represents a C-linked tetrazolyl group.

Claim 30

A process as claimed in any one of Claims 1 to 9 for the preparation of a compound wherein R 4 and R 5 each independently represents a hydrogen atom.

Claim 31

A process as claimed in Claim 1 or 2 for the preparation of a compound of the general formula (I) or a physiologically acceptable salt, solvate or metabolically labile ester thereof wherein R 1 represents a hydrogen atom or a halogen atom ; Ar represents the group R 3 represents a C-linked tetrazolyl group ; R 4 and R 6 each independently represent a hydrogen ; Het represents an N-linked imidazolyl group substituted at the 2-position by a C 1-6 alkyl or group, the imidazolyl group being substituted at the 4- and 5-positions by two further substituents selected from a halogen atom or a, ―(CH 2 ) n COR 7 group ; R 7 represents a hydroxy group ; and n represents an integer from 0 to 4.

Claim 32

A process as claimed in Claim 1 or 2 for the preparation of a compound selected from : 1-[[3-bromo-2-[2-(1 H-tetrazol-5-yl)phenyl]-5-benzo[b]thiophenyl]methyl]-2-butyl-4-chloro-1 H-imidazo le-5-carboxylic acid ; 1-[2-[2-(1 H-tetrazol-5-yl)phenyl]-5-benzo[b]thiophenyl]methyl]-2-butyl-4-chloro-1 H-imidazole-5-carb oxylic acid ; and physiologically acceptable salts, solvates and metabolically labile esters thereof.