Azaindenes

Claim 2

An azaindene derivative of the formula I wherein A, together with the adjacent vinylene group of the imidazole moiety completes an azene ring selected from pyridine, pyrimidine, pyridazine or pyrazine ring; R¹ is (1-8C)alkyl, (3-8C)cycloalkyl, (3-8C)-cycloalkyl(1-4C)alkyl, phenyl or phenyl(1-4C)alkyl; R² is hydrogen, (1-4C)alkyl, (1-4C)alkoxy, halogeno, trifluoromethyl, cyano or nitro; R³ and R⁴ are optional substituents on the said azene ring, independently selected from hydrogen, (1-4C)alkyl, (3-8C)cycloalkyl, (1-4C)alkoxy, halogeno, trifluoromethyl, cyano, hydroxy, hydroxymethyl, formyl, and nitro; or when A together with the imidazole moiety to which it is attached is an imidazo[4,5- b ]pyridine or imidazo[4,5- c ]pyridine group, R³ and R⁴ when they are on adjacent carbon atoms of A form a trimethylene or tetramethylene group, or together with the adjacent vinylene group of A complete a benzene ring, the latter optionally bearing a halogeno, (1-4C)alkyl or (1-4C)alkoxy substituent; or when A together with the imidazole moiety to which it is attached is other than a 1 H -imidazo[4,5- c ]pyridine ring, one of R³ or R⁴ is a carboxy or (1-6C)alkoxycarbonyl group and the other is as defined above; X is phenylene optionally bearing a substituent selected from (1-4C)alkyl, (1-4C)alkoxy and halogeno, or X is a direct bond between the adjacent phenyl and methylene moieties; and Z is 1 H -tetrazol-5-yl or a group of the formula -CO.OR⁵ or -CO.NH.SO₂.R⁶ in which R⁵ is hydrogen or a non-toxic, biodegradable residue of a physiologically acceptable alcohol or phenol, and R⁶ is (1-6C)alkyl, (3-8C)cycloalkyl or phenyl; and wherein any of said phenyl moieties may be unsubstituted or bear one or two substituents independently selected from (1-4C)alkyl, (1-4C)alkoxy, halogeno, cyano and trifluoromethyl; or a physiologically acceptable salt thereof except when R⁵ is other than hydrogen and R³ or R⁴ is other than carboxy.

Claim 3

A compound as claimed in claim 1 wherein R¹ is methyl, ethyl, propyl, butyl, isobutyl, sec -butyl, pentyl, hexyl, cyclopropyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl, 2-cyclopentylethyl, phenyl, benzyl, 1-phenylethyl or 2-phenylethyl; R² is hydrogen, methyl, ethyl, methoxy, ethoxy, fluoro, chloro, bromo, iodo, trifluoromethyl, cyano or nitro; R³ and R⁴ are optional substituents on the said azene ring, independently selected from hydrogen, methyl, ethyl, cyclopropyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, fluoro, chloro, bromo, iodo, trifluoromethyl, cyano, hydroxy, hydroxymethyl, formyl, and nitro; or when A together with the imidazole moiety to which it is attached is an imidazo[4,5- b ]pyridine or imidazo[4,5- c ]pyridine group, R³ and R⁴ when they are on adjacent carbon atoms of A form a trimethylene or tetramethylene group, or together with the adjacent vinylene group of A complete a benzene ring, the latter optionally bearing a fluoro, chloro, bromo, iodo, methyl, ethyl, methoxy or ethoxy substituent; or when A together with the imidazole moiety to which it is attached is other than a 1 H -imidazo[4,5- c ]pyridine ring, one of R³ or R⁴ is a carboxy, methoxycarbonyl, ethoxycarbonyl or propoxycarbonyl group and the other is as defined above; X is phenylene optionally bearing a substituent selected from methyl, ethyl, methoxy, ethoxy, fluoro, chloro, bromo and iodo, or X is a direct bond between the adjacent phenyl and methylene moieties; R⁵ is hydrogen or a residue derived from a (1-6C)alkanol, phenol or glycerol; and R⁶ is methyl, ethyl, propyl, isopropyl, butyl, pentyl, cyclobutyl, cyclopentyl, cyclohexyl or phenyl; and wherein any of said phenyl moieties may be unsubstituted or bear one or two substituents independently selected from methyl, ethyl, methoxy, ethoxy, fluoro, chloro, bromo, cyano and trifluoromethyl.

Claim 4

A compound of the formula Ia wherein R¹, R², R³, R⁴, X and Z have any of the values as defined in claim 1 or 2; or the physiologically acceptable salts thereof.

Claim 5

A compound as claimed in claim 1, 2 or 3 wherein R¹ is (1-6C)alkyl; R² is hydrogen or halogeno; R³ and R⁴ are selected from hydrogen, halogeno, (1-6C)alkyl, (1-6C)alkoxy, hydroxymethyl and hydroxy; X is a direct bond or p -phenylene; and 2 is selected from 1 H -tetrazol-5-yl, carboxy and a group of the formula -CO.NH.SO₂.R⁶ in which R⁶ is (1-6C)alkyl, (3-8C)cycloalkyl or phenyl, wherein Z is attached at the 2- or 4-position relative to X.

Claim 6

A compound as claimed in claims 1-4 wherein X is p -phenylene; and Z is 1 H -tetrazol-5-yl attached at the 2-position relative to X.

Claim 7

A compound of the formula I wherein A, R¹, R², X and Z have any of the meanings defined in claim 1; and R³ and R⁴ are optional substituents on A independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy, halogeno, trifluoromethyl, cyano and nitro; or a physiologically acceptable salt thereof except when R⁵ is other than hydrogen.

Claim 8

A compound as claimed in any preceding claim wherein R¹ is butyl.

Claim 9

A compound of the formula I selected from 2-butyl-3-[(2′-(1 H -tetrazol-5-yl)biphenyl-4-yl)methyl]-3 H -imidazo­[4,5- b ]pyridine; 2-butyl-4-hydroxy-3-[(2′(1 H -tetrazol-5-yl)biphenyl-4-yl)methyl]-­3 H -imidazo[4,5- d ]pyridazine; 2-butyl-7-methyl-3-[(2′-(1 H -tetrazol-5-yl)biphenyl-4-yl)methyl]-­ 3 H -imidazo[4,5- b ]pyridine; 2-butyl-5-methyl-3-[(2-(1 H -tetrazol-5-yl)biphenyl-4-yl)methyl]-­3 H -imidazo[4,5-b]pyridine; 2-butyl-7-chloro-3-[(2′-(1 H -tetrazol-5-yl)biphenyl-4-ylmethyl]-­3 H -imidazo[4,5- b ]pyridine; and 2-butyl-4-hydroxy-3-[(2′(1 H -tetrazol-5-yl)biphenyl-4-yl)methyl]-­3 H -imidazo[4,5- c ]pyridine; and 2-butyl-6-(hydroxymethyl)-3-[(2′-(1H-tetrazol-5-yl)biphenyl-4-yl)­methyl]imidazo[4,5- b ]pyridine; and the physiologically acceptable salts thereof.

Claim 10

A compound of the formula I selected from 2-butyl-3-[(2′-(1 H -tetrazol-5-yl)biphenyl-4-yl)methyl]-3 H -imidazo­[4,5- b ]pyridine; 2-butyl-4-hydroxy-3-[(2′(1 H -tetrazol-5-yl)biphenyl-4-yl)methyl]-­3 H -imidazo[4,5- d ]pyridazine; 2-butyl-7-methyl-3-[(2′-(1 H -tetrazol-5-yl)biphenyl-4-yl)methyl]-­ 3 H -imidazo[4,5- b ]pyridine; 2-butyl-5-methyl-3-[(2-(1 H -tetrazol-5-yl)biphenyl-4-yl)methyl]-­3 H -imidazo[4,5-b]pyridine; 2-butyl-7-chloro-3-[(2′-(1 H -tetrazol-5-yl)biphenyl-4-ylmethyl]-­3 H -imidazo[4,5- b ]pyridine; and 2-butyl-4-hydroxy-3-[(2′(1 H -tetrazol-5-yl)biphenyl-4-yl)methyl]-­3 H -imidazo[4,5- c ]pyridine; and 2-butyl-6-(hydroxymethyl)-3-[(2′-(1H-tetrazol-5-yl)biphenyl-4-yl)­methyl]imidazo[4,5- b ]pyridine; and the physiologically acceptable salts thereof.

Claim 11

A salt as claimed in any one preceding claim which is selected from alkali metal, alkaline earth metal, aluminium and ammonium salts, and from salts with organic bases affording physiologically acceptable cations, and for those compounds of formula I which are basic, salts with acids affording physiologically acceptable anions.

Claim 12

A process for the manufacture of a compound of formula I or a physiologically acceptable salt thereof, as defined in claim 1 which is characterised in that: a) For those compounds in which Z is carboxy, a carboxylic acid derivative of the formula II in which Q is a protected carboxy group selected from (1-6C)alkoxycarbonyl, phenoxycarbonyl, benzyloxycarbonyl and carbamoyl, is converted to carboxy; b) For those compounds of formula I wherein Z is tetrazolyl, a compound of the formula III in which L is a suitable protecting group affixed to a nitrogen of the tetrazolyl moiety, is deprotected; c) For those compounds of formula I wherein Z is a group of the formula -CO.OR⁵ , an imidazole derivative of the formula IV is reacted with a compound of the formula V wherein Hal. stands for a suitable leaving group; or d) A diamino derivative of the formula VII is reacted with a carboxylic acid of the formula R¹.CO₂H or a (1-4C)alkyl orthoester thereof; whereafter, when a compound of the formula I is required wherein Z is a group of the formula -CO.NH.SO₂R⁶ or a group of the formula -CO.OR⁵ in which R⁵ is other than hydrogen, a carboxylic acid of the formula I in which Z is carboxy (or a reactive derivative of said acid) is reacted with a sulphonamide of the formula NH₂.SO₂R⁶ or a hydroxy compound of the formula HO.R⁵ , or with a salt thereof; whereafter, when a salt of a compound of formula I is required, it is obtained by reaction with the appropriate base or acid affording a physiologically acceptable ion, or by any other conventional salt formation procedure; and when an optically active form of a compound of formula I is required, one of the processes (a)-(d) is carried out using an optically active starting material, or the racemic form of a compound of formula I is resolved by reaction with an optically active form of a suitable organic base or acid, followed by conventional separation of the diastereoisomeric mixture of salts thus obtained, and liberation of the required optically active form of said compound of formula I by conventional treatment with acid or base; and wherein A, R¹, R², R³, R⁴, X and Z have any of the meanings defined in any of claims 1-7 unless otherwise stated.

Claim 13

A pharmaceutical composition which comprises a compound of the formula I or Ia, or a physiologically acceptable salt thereof, as claimed in any of claims 1 to 9, together with a pharmaceutically acceptable diluent or carrier.

Claim 14

A compound of the formula III wherein A, R¹, R², R³, R⁴ and X have any of the meanings defined in any of claims 1-7, and L is a protecting group.