CA2092852A1

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Publication number: CA2092852A1
Application number: CA002092852A
Authority: CA
Inventors: Pierre Dodey; Didier Pruneau; Patrice Renaut; Michel Bondoux
Original assignee: Individual
Current assignee: Fournier Industrie et Sante SAS
Priority date: 1992-04-01
Filing date: 1993-03-29
Publication date: 1993-10-02
Also published as: FI931414L; CN1081438A; EP0564356A1; TW232012B; JPH06263743A; ZA932351B; FR2689508B1; MX9301882A; NO931186D0; FR2689508A1; HU9300942D0; FI931414A7; KR930021622A; AU3554693A; NO931186L; HUT64752A; FI931414A0

Abstract

ABSTRACT OF THE DISCLOSURE

The present invention relates to the phenyl-aminomethylimidazoles of the formula (I) (in which the groups R1 to R7 are defined as indicated in the description).
It further relates to their method of prepara-tion and to their application in therapeutics as angiotensin II antagonists, which are useful in the treatment of hypertension, circulatory disorders and glaucoma.

Description

- 1 - 2~2~~3~

Imidazole derivatives, their method of preparation and their application in therapeutics 05 The present invention relates to imidazole derivatives, to their method of preparation and to their application in therapeutics as agents useful in the treatment of hypertension, circulatory disorders and glaucoma.
A number of imidazole derivatives are already known which are angiotensin II inhibitors useful as antihypertensives. `
Patent applications EP-A-403 158 and EP-A-403 159 describe imidazolylalkenoic acids carrying an unsaturated chain in the 5-position of the imidazole ring. Patent application EP-A-465 368 describes , sulfur-containing imidazole derivatives. Patent appli-cation WO-A-91/00277 describes substituted imidazoles carrying an aldehyde group in the 5-position of the ` 20 imidazole ring. Patent application EP-A-427 463 des-cribes substituted N-(imidazolyl)alkylalanine deri-vatives carrying an amino acid in the 5-position of the imidazole ring. Patent application EP-A-324 377 des-cribes imidazole derivatives which are recommended as diuretics, antiinflammatories and antihypertensives.
Patent application EP-A-253 310 describes imidazole derivatives carrying a hydroxymethyl substituent in the 5-position of the imidazole ring.
None of these documents of the prior art des-;~ 30 cribes or suggests imidazole derivatives carrying a phenylaminomethyl substituent in the 5-position of the , imidazole ring.
-~ The present invention therefore proposes imi-dazole derivatives carrying a phenylaminomethyl substi-; 35 tuent in the 5-position of the imidazole ring.

. . ,: ~: ,.. ,, .: ,, , ::: , :

2 ~ 3 2 The compounds according to the invention are selected from the group consisting of:
(i) the phenylaminomethylimidazoles of the formula N~ 2 Rl3 3 Rl R7$~ ( I ) ~\ J 6 R6 ~ ~/ ~ Rs in which:
- Rl is a C1-C4-alkyl group;
- R2 is the hydrogen atom, a halogen, a Cl-C4-alkylthio group or a C1-C3-perfluoroalkyl group;
- R3 is the hydrogen atom, a Cl-C4-alkyl group or a group COR~, in which R~ is a Cl-C4-alkyl group;
20 - R4 is in the 3-, 4-, 5- or 6-position and is the hydrogen atom, one or more Cl-C4-alkyl, Cl-C4-alkoxy, ,~
azido or nitro groups or one or more halogens, or forms a 2-aminonaphthyl group with the aminophenyl group to which it is bonded;
- R5 is a hydrogen atom or a halogen;
- R~ and R7, which are identical or different, are each a tetrazol-5-yl group or a group COR9, in which R9 is:
- a hydroxyl group, - a Cl-Cl~-alkoxy group, - a cyclopropylmethoxy group, - a phenoxy group, - a benzyloxy group, - a 2-phenylethoxy group, - a glyceryl group, - an isopropylideneglyceryl group, .. : . . : ; : .
- ~ : .. , : .. . ........ . .
. ~ :

. ., . ~ . . ~ . .

- a 2-methoxyethoxy group, - a 2-oxobutoxy group, - a 1-methyl-2-oxobutoxy group, - a 2-(N,N-diethylamino)ethoxy group, 05 - a morpholinoethoxy group, - an N-(ethoxy)nicotinamide group, - a group O-CHR15-O(CO)-Rl2, in which R15 is the hydrogen atom or a C1-C3-alkyl group and Rl2 is a : C1-C7-alkyl group, a cyclopentyl group, a cyclohexyl . 10 group, a cyclopentylmethyl group or a cyclohexylmethyl ; group, - an oxyacetate group of the formula O-CHR1~-CO2-Rl~, in which R1G and R17 are each independently the hydrogen atom or a C1-C5-alkyl group, - an oxyacetamide group of the formula O-CH2-CO-NR1oR11, in which R1o and R11, which are identical or different, are each a Cl-C4-alkyl group or a hy-droxyethyl group or form a 4-methylpiperazin-1-yl group with the nitrogen atom to which they are bonded, or - an amino group of the formula -NRl8R19, in which Rl 8 and R19 are each independently the hydrogen atom, a C1-C~-alkyl group, a methoxy group or a 2-(N,N-dimethylamino)propyl group, or -NR18R19 is an amino acid residue of the glycine or valine structure in which the acid group is optionally protected in the . form of an ester or amide;
~ RG is also:
, - a group CORI 3 ~ in which R13 is a methylsul-fonylamino group of the formula -NH-SO2-CH3 or an aryl-sulfonylamino group of the formula ~=\~ R,4 --NH- SO2~>

.,.. .. :., c~

in which Rl4 is the hydrogen atom, a halogen, an azido group, a C1-C4-alkyl group or a methoxy group and can be located in the ortho-, meta- or para-position; and - R3 and R7 taken together can form, with the nitrogen 05 atom and the phenyl group to which they are respecti-vely bonded, a 2-carboxyindol-1-yl or 2-ethoxycarbonyl-indol-1-yl ortho-fused nitrogen-containing heterocycle;
and (ii) the addition salts of the compounds of formula I
with mineral and organic acids or with mineral and organic bases.
; Cl-C7-Alkyl group is understood here as meaning a linear, branched or cyclic alkyl group containing up to 7 carbon atoms. The preferred alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl and pentyl groups.
C1-Cl6-Alkoxy group is understood here as meaning a group in which the alkyl radical is linear, branched or cyclic and contains up to 16 carbon atoms.
The preferred alkoxy groups are methoxy, ethoxy, pent-oxy and cyclopropylmethoxy groups.
C -C4-Alkylthio group is understood here as meaning a group in which the alkyl radical is linear or branched and contains up to 4 carbon atoms. The pre-ferred alkylthio groups are methylthio and ethylthio groups.
Halogen is understood here as meaning the fluorine atom, the chlorine atom, the bromine atom or the iodine atom.
The preferred C -C3-perfluoroalkyl groups will be trifluoromethyl and perfluoroethyl groups.
The preferred addition salts with mineral and organic acids will be~ the addition salts formed with hydrochloric, hydrobromic, sulfuric, nitric, phos-phoric, maleic, malic, acetic, glutamic, tartaric, ` : ` ... .: . :

. . :: , . :: . , lactic, citric, aspartic, oleic, gluconic, ascorbic, valeric, succinic, ethylsuccinic, fumaric, oxalic, gallic, pivalic, capric, decanoic, heptanoic, propio-nic, caproic, stearic, isethionic, ethanedisulfonic, 05 methanesulfonic, naphthalenesulfonic and metasulfo-benzoic acids.
The preferred addition salts with mineral or organic bases will be the addition salts formed with sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, manganese hydroxide, lithium hydroxide, lysine, cysteine, arginine, mono-ethanolamine, meglumine, betaine, diethylamine and dicyclohexylamine.
The preferred compounds according to the invention are the compounds of formula I in which RG
and R7 are a sulfonylaminocarbonyl group or a group COOH, as well as their salts obtained by reaction with an organic or mineral base. The compounds of formula I
salified by reaction with an organic or mineral acid will be particularly preferred.
The compounds of formula I according to the invention can be prepared by a method wherein:
(a) a compound of the formula ;
R'2 N /
R 1 ~N~ ~ /X (II') ,~J
R'6 ~J\ R~5 in which:
35 ~ R~1 iS a C1-C4-alkyl group;

2~

~ R'2 ls the hydrogen atom, a halogen, a C1-C4-alkyl-thio group or a Cl-C3-perfluoroalkyl group;
~ R's is a hydrogen atom or a halogen;
- R'~ is a cyano group or a group COR'g, in which R'g is 05 a C1-Clfi-alkoxy group, a benzyloxy group or an iso-propylideneglyceryl group; and - X is a halogen, especially the chlorine atom, or a paratoluenesulfonyl group, is subjected to nucleophilic substitution by reaction with a compound of the formula ,~

R ~N ~ 4 (III') ; in which:
- R'3 is the hydrogen atom or a Cl-C4-alkyl group;
- R'4 is in the 3-, 4-, 5- or 6-position and is the hydrogen atom, one or more C1-C4-alkyl, Cl-C4-alkoxy, azido or nitro groups or one or more halogens, or forms a 2-aminonaphthyl group with the aminophenyl group to which it is bonded;
-- - R', is a cyano group or a group COR'g, in which R'g is:
- a C~-Cl~-alkoxy group, a benzyloxy group, an isopropylideneglyceryl group, a phenoxy group, a 2-phenylethoxy group, a 2-methoxyethoxy group, a 2-oxo-butoxy group, a l-methyl-2-oxobutoxy group or a 2-(N,N-diethylamino)ethoxy group, - a group O-CHRls-O(CO)-Rl2, in which Rl5 is the hydrogen atom or a C1-C3-alkyl group and R1z is a C1-C7-alkyl group, a-cyclopentyl group, a cyclohexyl group, a cyclopentylmethyl group or a cyclohexylmethyl group, , . - , : . : , : -. : .

- . - .:: -;-. .. -. , . . . :
- . : , : ::: ~: ~ ,, ,-, ~ - , : . .
- . . . : . ,: ~. .. . ,: .. :: :. : - . . . .

r ~ ~

- an oxyacetate group of the formula 0-CHR1,-C02-Rl~, in which R1 G and R1 7 are each independently the hydrogen atom or a Cl-C5-alkyl group, - an oxyacetamide group of the formula 0-CH2-05 C0-NRloRl1, in which Rlo and Rl1, which are identical or different, are each a C,-C~-alkyl group or a hy-droxyethyl group, or - an amino group of the formula -NR1~R19, in which R18 and Rl9 are each independently the hydrogen atom, a C1-C4-alkyl group, a methoxy group or a 2-(N,N-dimethylamino)propyl group, or -NRl8Rlg is an amino acid residue of the glycine or valine structure in .which the acid group is optionally protected in the form of an ester or amide; and - R'3 and R', taken together can form, with the nitrogen atom and the phenyl group to which they are respecti-vely bonded, a 2-carboxyindol-1-yl or 2-ethoxycarbonyl-indol-1-yl ortho-fused nitrogen-containing heterocycle, in an anhydrous medium, in the presence or absence of a polar or non-polar and aprotic solvent, for example toluene, xylenes, tetrahydrofuran, dimethylformamide, chlorinated hydrocarbons, ethers, dioxane, N-methyl-pyrrolidin-2-one, N,N'-dimethylpropyleneurea or di-methyl sulfoxide, and in the presence or absence of a .25 strong base, for example triethylamine, 2,6-lutidine, ` sodium or potassium hydride, potassium or lithium hexamethyldisilylamide or lithium diisopropylamide, at a rate of 1 mol of compound II' to 1 to 20 mol of compound III', at a temperature between room tempera-ture (15-25 C) and about 200 C, for 0.1 to 12 hours, to give a compound of the formula .

~. . ... , . . . : . ., - : :

~ 3'~

N ~ l3 ~

05 ~ R'7 6 (I') R' ~R~s in which R'1, R'2, R'3, R'~, R'5, RIG and R~7 are defined as indicated above; and (b) if necessary, the resulting compounds of formula I' can be subjected to the following treatments:
(i) the compounds of formula I' in which at least one of the groups R'~; and R~7 is a group COR~9 in which R~9 is a Cl-C1~-alkoxy group are saponified by the methods known to those skilled in the art, especially in the presence of a strong base, for example an aqueous solution of sodium or potassium hydroxide, in dimeth-oxyethane or an alcohol such as methanol, to give a compound of formula I in which RG and R7 are a group : COOH or RG is a group COOH and R7 is a group COR9 in which R9 is a Cl-C1~-alkoxy group;
(ii) the compounds thus obtained in stage (i) are esterified by the methods known to those skilled in the art, especially by reaction with an appropriate alcohol or by reaction with an appropriate halogenated deriva-tive, to give a compound of formula I in which R~; and R7 are a group COR9 in which R9 is as defined for the groups R~9 indicated above;
-, (iii) methylsulfonamide or an arylsulfonamide of the ' formula J
q 35 .

9 ~ 2 8 ~ 2 R~4 ~ SO2-NH2 05 in which R14 is the hydrogen atom, a halogen, an azido group, a Cl-C4-alkyl group or a methoxy group, is acylated with a monoacid obtained in stage (i) by the methods known to those skilled in the art, especially in the presence of a coupling reagent, for example -~10 l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydro-:chloride or N,N-dicyclohexylcarbodiimide, to give a compound of formula I in which RG is a group CORl3 in which Rl3 is a methylsulfonylamino group of the formula -NH-SO2-CH3 or an arylsulfonylamino group of the for-mula . ~ R14 --NH- SO2~

:, in which Rl4 is defined as indicated above, R, is a `group COR9 in which R9 is a Cl-ClG-alkoxy group, and ~R1~ R2, R3, R4 and R5 are defined as indicated above :for R 1~ R 2~ R'3, R'4 and Rl5 respectively;
(iv) the compounds of formula I' in which R'3 is the hydrogen atom and R'l, R'2, R~4, R~5, R'~ and Rl7 are defined as indicated above are acylqted by the methods known to those skilled in the art, especially by reac-`tion with an acid anhydride, for example acetic anhy--30 dride, to give a compound of formula I in which R3 is a group CORn in which R8 is a Cl-C4 alkyl group, and Rl, `R2, R4, Rs~ RG and R7 are defined as indicated above for R 1~ R 2 ~ R 4, R'5, R'~ and R'7 reSPeCtiVe1Y;
.(v) if necessary, the compounds of formula I' in which .~35 at least one of the groups RIG and R~7 is a group COR'g :~`

- - . ~ . . .- . . .

- lo 2~w~

in which R'g is a Cl-C4-alkoxy group, a benzyloxy group or an isopropylideneglyceryl group are deprotected by the methods known to those skilled in the art, espe-cially by treatment in an acid medium or by catalytic 05 hydrogenation, to give a compound of formula I in which at least one of the groups R~j or R, is a group COOH or CO-glyceryl and the other group is a group CORg in which Rg is defined as indicated above for R'g; and (vi) the compounds of formula I' in which R'~ or R'7 is a cyano group are converted to a compound of formula I
in which RG or R, is a tetrazol-5-yl group by the methods known to those skilled in the art, especially by the 1,3-dipolar cycloaddition of trialkyltin or tri-aryltin azides.
To obtain the compounds of formula II', it is recommended to reduce an aldehyde of the formula N ~ R~2 ~ ~ H
~ N ~ (IV) '~

R' ~ R~s in which R'1, R'2, R'5 and R'~ are defined as indicated above, by the methods known to those skilled in the . art, especially by reaction with NaBH4 or KBH4 in an 0 alcohol, to give an alcohol of the formula . ~
~, . .

.
~` 35 :;
,: .

~: . - . :. :: : . .

. ~

2 ~ ~

N ~
Il \\
Rl - N ~
05 ¦ OH (V) ,~
R'6 R's 10 in which R'l, R'Z, R'5 and R~G are defined as indicated above, and then to convert the resulting alcohol to a derivative of formula II', especially a chlorinated derivative, by the methods known to those skilled in the art, especially by reaction with thionyl chloride in an inert solvent such as a halogenated solvent.
The i~termediates of formula IV in which:
(i) R'l is an n-propyl group, R'2 is a hydrogen atom or a halogen, R'5 is the hydrogen atom and RIG is a cyano group or a group COR'g in which Rl9 is a C1-C1G-alkoxy group or a benzyloxy group, or (ii) R'l is an n-butyl group, R'2 and R'5 are the hydrogen atom and RIG is a group COR'g in which R~9 is a t-butoxy or benzyloxy group, are novel compounds and form one of the subjects of the invention.
;l~The intermediates of formula V in which R~1 is a C1-C4-alkyl group, R'2 is the hydrogen atom or a halogen, R~5 is the hydrogen atom and R~G is a group COR'g in which R~9 is a Cl-ClG-alkoxy group or a ; 30 benzyloxy group are novel compounds and form one of the subjects of the invention.
The intermediates of formula II' in which R'l is an n-butyl group, R'2 and R~5 are the hydrogen atom and R~G is a group COR~9 in which R~9 is a t-butoxy or benzyloxy group are novel compounds and form one of the , ~
:~:
:`~

1` ~ -, , ~ - , ; . , .. . ; ., ; .;

, . : : . ,, . .~ ~ . . .. .
: . ~ ~, ,,, . - ,, - 12 ~ 3 subjects of the invention.
The invention will be understood more clearly from the description of the following Preparatory Examples, in which the Preparations refer to the inter-05 mediates and the Examples refer to the products accor-ding to the invention. These Examples are intended to illustrate the invention without limiting its scope.

2-Butyl-4-iodo-lH-imidazole-5-carboxaldehyde A solution of 70.5 g (128.5 10-3 mol) of ammo-niacal cerium nitrate in 58 ml of water is added drop-wise to a suspension, at 15C, of 16 g (57-10-3 mol) of 15 2-butyl-4-iodo-lH-imidazole-5-methanol in 48 ml of acetic acid. The reaction mixture is stirred at room temperature for 24 hours. A 10 N solution of sodium hydroxide is then added until the pH is 6. The preci-pitate formed is extracted with ethyl acetate, washed with water and then dried over magnesium sulfate to give 14.7 g (yield: 93%) of a beige solid.
-~ M.p. = 90 C

! PREPARATION 2 Methyl 4-r~4-chloro-5-formyl-2-propyl-lH-imidazol-l-vl~methyllbenzoate 17.4 g (126 10-3 mol) of potassium carbonate are added to a solution of 18.15 g (105 10-3 mol) of 4-chloro-2-propyl-lH-imidazole-5-carboxaldehyde and 28.9 g (126 10-3 mol) of methyl 4-bromomethylbenzoate ~y in 275 ml of dimethylformamide. The reaction mixture is heated at 40 C for 2 hours, with stirring, and then cooled, poured into water and extracted with ethyl ace-tate. The organic phases are washed with water until ~ù
'``
:
~, :.
,. : . : : , . ~. , :.

. . .:: :. - : ~ :: . : : ~
- . : . : . . .... : : :.
:,-: - : -- 13 - 2~

the washings are neutral, dried over magnesium sulfate and concentrated. The crude solid obtained is recrys-tallized from ethanol to give 28 g (yield: 83%) of a white solid.
05 M.p. = 89 C
The products of Preparations 9, 10, 11 and 31 are obtained by an analogous procedure.

Methyl 4-[(5-formyl-2-propyl-1H-imidazol-l-yl)methyll-benzoate 7.1 g (72 10-3 mol) of potassium acetate and then, under nitrogen, 3.48 g of 5% palladium-on-char-coal are added to a solution of 23.2 g (72-10-3 mol) of methyl 4-[(4-chloro-5-formyl-2-propyl-lH-imidazol-1-yl)methyl]benzoate in 230 ml of methanol. The suspen-sion obtained is stirred under a hydrogen atmosphere at room temperature for 3 days. The catalyst is filtered off, the methanol is evaporated off, the residue is taken up in ethyl acetate and the resulting solution is washed with water until the washings are neutral.
After drying over magnesium sulfate, the solution is concentrated and the oily crude product obtained is chromatographed on silica using a cyclohexane/acetone mixture (7/3; v/v) as the eluent. Evaporation of the eluent gives 19 g (yield: 91.6%) of a white solid.
M.p. = 72 C
The following products were obtained by an analogous procedure:
1.l-Dimethylethyl 4-[(2-butyl-5-formyl-lH-imidazol-l-vl~methyl~benzoate (Preparation 12) H NMR (300 MHz; CDCl3; ppm) 0.89 (t, 3H); 1.31 (m, 2H); 1.57 (s, 9H); 1.69 (m, 2H);
2.66 (t, 2H); 5.82 (s, 2H); 7.03 (d, 2H); 7.81 (s, lH);

' ' . ~ . . ' ~
~ . ,: . . . , -~2~?

7.93 (d, 2H); 9.66 (s, lH).
Ethyl 4-[(2-butyl-5-formyl-lH-imidazol-l-yl!methyll-benzoate ~Preparation 32) lH NMR (300 MHz; CDC]3; ppm) 05 0.89 (t, 3H); 1.23 - 1.40 (m, 5H); 1.63 - 1.74 (m, 2H);
2.64 (t, 2H); 4.35 (q, 2H); 5.60 (s, 2H); 7.04 (d, 2H);
7.82 (s, lH); 7.97 (d, 2H); 9.67 (s, lH).

Methyl 4-r(2-butyl-5-formyl-4-trifluoromethyl-lH-; imidazol-1-yl)methyllbenzoate A solution of 32 ml of dibromodifluoromethane in 32 ml of dimethylformamide is added in 2 hours to a 15 suspension of 82 g of cadmium powder in 183 ml of dimethylformamide and room temperature. The reaction mixture is stirred for 2 hours at room temperature and then left to stand for 30 minutes. 8.34 g (58-10-3 mol) of cuprous bromide and then a solution of 7.08 g 20 (16.6-10-3 mol) of methyl 4-[(2-butyl-5-formyl-4-iodo-lH-imidazol-l-yl)methyl]benzoate in 50 ml of dimethyl-;l formamide are added to a mixture of 70 ml of the above solution in 75 ml of hexamethylphosphorotriamide at 0 C. The reaction mixture is heated at 70 C for 4 hours. After the mixture has cooled, 600 ml of water ; are added and extraction is carried out with ethyl acetate. The organic phases are washed with water, dried over magnesium sulfate, filtered and evaporated under reduced pressure. The resulting oil is purified ; 30 by chromatography on silica using a toluene/ethyl ace-~ tate mixture (9/1; v/v) as the eluent to give 5.71 g `~ (yield: 93%) of an ochre solid.
M.p. = 59 C

- 15 ~ 2~9 2 ~5 2 4-~(2-Butyl-5-formyl-lH-imidazol-l-yl)methyllbenzoic acid 05 25 ml of water and 3 g (75 10-3 mol) of sodium hydroxide are added to a solution of 16 g (53.3 10-3 mol) of methyl 4-[(2-butyl-5-formyl-lH-imidazol-1-yl)-methyl]benzoate in 100 ml of methanol. The reaction mixture is refluxed for 5 hours. The methanol is eva--;10 porated off under reduced pressure and 150 ml of water are added to the residue. The mixture is washed with twice 50 ml of ethyl acetate. The aqueous phase is acidified to pH 6 with a 1 N solution of hydrochloric `~acid and extracted with 2 times 100 ml of an ethyl ;15 acetate/n-butanol mixture (80/20; v/v). The organic phases are washed with water, dried over magnesium sulfate, filtered and evaporated under reduced pressure to give 14 g (yield: 94%) of a yellow solid.
M.p. = 148 C
The product of Preparation 33 is obtained by a procedure analogous to Preparation 5.
:.:
~ PREPARATION 6 ., Phenylmethyl 4-[(2-butyl-5-formyl-lH-imidazol-l-yl)-methyl~benzoate 5 . 4 g ( 50 10-3 mol) of benzyl alcohol, 5.85 g ~48~10-3 mol) of 4-dimethylaminopyridine and 9.17 g (48-10-3 mol) of 1-(3-dimethylaminopropyl)-3-ethyl-~;~30 carbodiimide hydrochloride are added to a solution of 13.5 g (47.2-10-3 mol) of 4-[(2-butyl-5-formyl-lH-imidazol-1-yl)methyl]benzoic acid in a mixture of 5 ml of dimethylformamide and 200 ml of dichloromethane.
The reaction mixture is stirred at room temperature for 20 hours and then washed with twice 60 ml of water.

;- , .
- , , , ~ i ,~ , . , .

The organic phase is dried over magnesium sulfate, fil-tered and evaporated under reduced pressure. The resi-due is purified ~y chromatography using a hexane/
acetone mixture (70/30; v/v) as the eluent to give 17 g 05 (yield: 95%) of a yellow oil.
1H NMR (300 MHz; CDCl3; ppm) 0.88 (t, 3H); 1.35 (m, 2H); 1.72 (m, 2H); 2.65 (t, 2H);
5.34 (s, 2H); 5.62 (s, 2H); 7.04 (d, 2H); 7.4 (m, 5H);
7.80 (s, lH); 8.03 (d, 2H); 9.66 (s, lH).
The product of Preparation 34 and the following products are obtained by an anal~gous procedure:
Pentyl 4-r(2-butyl-5-formyl-1H-imidazol-1-yl)methyl]-benzoate ~PreDaration 35) ~` lH NMR (300 MHz; CDCl3; ppm) `I 15 0.89 (m, 6H); 1.18 - 1.40 (m, 5H); 1.62 - 1.77 (m, 5H);
2.63 (t, 2H); 4.29 (t, 2H); 5.63 (s, 2H); 7.05 (d, 2H);
7.81 (s, lH); 7.97 (d, 2H); 9.67 (s, lH).
Butyl 4-~(2-butyl-5-formyl-lH-imidazol-l-yl ! methyl~-penzoate (Preparation 36!
' 20 1H NMR (300 MHz; CDCl3; ppm) 1 0.86 (t, 3H); 0.96 (t, 3H); 1.31 - 1.49 (m, 4H); 1.64 -1.78 (m, 4H); 2.63 (t, 2H); 4.30 (t, 2H); 5.62 (s, 2H);
7.04 (d, 2H); 7.81 (s, lH); 7.97 (d, 2H); 9.67 (s, lH).
2-Methylpropyl 4-[(2-butyl-5-formyl-lH-imidazol-1-yl~-methyllbenzoate (Preparation 37) i~ lH NMR (300 MHz; CDCl3; ppm) 0.88 (t, 3H); 0.99 (d, 6H); 1.31 - 1;38 (m, 2H); 1.64 -1.75 (m, 2H); 2.06 (m, lH); 2.63 (t, 2H); 4.08 (d, 2H);
5.63 (s, 2H); 7.05 (d, 2H); 7.81 (s, lH); 7.98 (d, 2H);
9.67 (s, lH).
Cyclopropylmethyl 4- r ( 2-butyl-5-formyl-lH-imidazol-l-vl~methyl~benzoate (Preparation 38 ~H NMR (300 MHz; CDCl3; ppm) 0.35 (m, 2H); 0.59 (m, 2H); 0.88 (t, 3H); 1.21 - 1.25 (m, lH); 1.29 - 1.40 (m, 2H); 1.60 - 1.75 (m, 2H); 2.63 ., : ., . ' : ,, ~: ' : ' ! ' ' ' ~.J ~

(t, 2H); 4.12 (d, 2H); 5.63 (s, 2H); 7.05 (d, 2H); 7.81 (s, lH); 7.97 (d, 2H); 9.67 (s, lH).

3-Methylbutyl 4-~(2-butyl-5-formyl-lH-imidazol-l-yl~-methyllbenzoate (Preparation 39l 05 lH NMR (300 MHz; CDCl3; ppm) 0.88 (t, 3H); 0.97 (d, 6H); 1.23 - 1.41 (m, 3H); 1.61 -1.82 (m, 4H); 2.63 (t, 2H); 4.35 (t, 2H); 5.63 (s, 2H);
7.05 (d, 2H); 7.81 (s, lH); 7.97 (d, 2H); 9.67 (s, lH).
Phenylmethyl 4-r(2-butyl-4-chloro-5-formyl-lH-imida~ol-l-yl)methyl~benzoate (Preparation 40l H NMR (300 MHz; CDCl3; ppm) 0.87 (t, 3H); 1.29 - 1.37 (m, 2H); 1.61 - 1.72 (m, 2H);
2~60 (t, 2H); 5.35 (s, 2H); 5.59 (s, 2H); 7.07 (d, 2H);
7.34 - 7.44 (m, 5H); 8.02 (d, 2H).

Methyl 4-r[2-butyl-5-formyl-4-methylthio-lH-imidazol-l-yllmethylJbenzoate ~ 20 3.24 g (4.62-l0-2 mol) of sodium thiomethylate ;~ are added to a solution of 3.87 g (1.15- 10-2 mol) of methyl 4-[(4-chloro-5-formyl-2-butyl-lH-imidazol-l-yl)-methyl]benzoate in 40 ml of methanol. The reaction mixture is refluxed for 4 hours, with stirring, and then cooled, poured into a 10% aqueous solution of citric acid at 0 C and extracted with ethyl acetate.
The organic phases are washed with water until the washings are neutral, dried over magnesium sulfate and concentrated. The oily residue obtained is chromato-graphed on silica using a toluene/ethyl acetate mixture (8/2; v/v) as the eluent. Evaporation of the eluent gives 2.8 g (yield: 70%) of a yellow solid.
M.p. = 72 - 74 C

, ':; - . , : .
- ~, . , : - - . .

' : ~ . ~ ~ . .. ' .

'2~8~2 ethyl 4- r ( 2-butyl-5-hydroxymethyl-lH-imidazol-1-yl)-methyllbenzoate 05 5.92 g (19.7-10-3 mol) of methyl 4-[(2-butyl-5-formyl-lH-imidazol-l-yl)methyl]benzoate are dissolved in 60 ml of methanol and the solution obtained is cooled with an ice bath. 895 mg (23.6-10-3 mol) of sodium borohydride are then added in portions over 30 minutes, with stirring. After 10 minutes, the methanol is evaporated off and the residue is diluted with water and extracted with methylene chloride. The combined organic phases are washed with water, dried over mag-nesium sulfate and concentrated to give 5.22 g (yield:
88%) of a white solid.
M.p. = 144 C
The products of Preparations 13 to 21 and 41 to 49 and the following product were prepared by an analogous procedure:

10 n-Bu Cl H H H
13 n-Pr Cl H H H 108 14 n-Bu Cl H S-CI H 90 :: . lS n-Bu Cl H 4-Cl H 116 17 n-Bu Cl H 4-NO~ H 136 18 n-Bu Cl H S-CH; H
i 19 n-Bu I H H H
20 n-Bu CF, H H H
21 n-Bu Cl Il H Cl 140 54 n-Bu Cl COCHl H H 142 75n-BII SC~I3 H H H
116n-Pr H H 4-NO. H
225n-Bu H H 4-N3 H 132 Note: * double melting point: 87 C, then 97 C

,~

- -, . . . . ~ - . . .

- 72 - 2~2~
:

TABLE I I
::
:' 05 R~
~ / R

R, --N~l R4 : ~J O ~ 5 HO

O
1~ EY R, ¦ R ¦ R, ¦ R~ Rs¦ M.p.~ C) ¦

32 n-Bll H ~ 1~ H H 234 n-BIl ~ 4-NO. H 250 36 n-Pr H I I H H 249 37 n-Bll Cl 1-1 3-CH, H 115 3~ n-Bll Cl Cll, H H 147 39 n-Bll Cl H 3,;-diCl H 220 n-Bll Cl 11 3,4,5-tl-i OCH, H 212 41 n-Btl Cl H H Cl 244 42 n Pr Cl H H H 246 ; 43 n-Bn CF, 11 H H 262 : 44 n-Bll I 11 H H 225 n-Bu Cl H ;-CH, H 232 46 n-Btl Cl H 4-NO. H 260 . ~ 48 n-Btl Cl H 4-Cl H 247 .. 49 n-Btl Cl H S-CI H 248 n-Btl Cl H H H 235 . 55 n-Btl Cl CO CIIl H H 230 : 198 n-Bu SCH3 H H H 207 199 n- Bn H I-l 6-CH3 H 225 200 n-Btl 11 11 6-Cl H 259 212 " p~- H ~l 4-NO. H 281 216 n-B~ 11 H 4-N3 H215(dec) ~ .

`~;

.. . . .. . ....

2~2~

TABLE I I I

~ ~NH~4 ,~ o~5 OR' RO ~W
.; 11 O
E.Y ¦ R, ¦ R I R n~ M.p.( C) 4 n-B~l l~ l Bn i Il-Bll H l t-Bu Bn 22 n-Bll Cl ! t-Bu CH, 102 23 n-Bll Cl l ~I CH, 181 2~ n-Bll I~ CH, 85 n-Bll ~1 I-I Bn 90 26 n-Bll H ¦ H Ig 92 27 n-Bll H Ig H 202 : 28 n-Bll H H Gl 123 29 n-Bu H Cl H 134 S3 I~Bu H 1~ K 206 ~; 62 n-Bll H Ig Bn ; 2 5 63 n-Bu H MO E ~IO E
64 ll-Bu H NAE ~AE 84 n-Bll H Ig Ig 63 n-Bll H AA E ~AE 55 ~ 69 n-Bll H Y-t-Bu Y-t-Bu :~- 70 n-Bll- H Pz Pz 71 n-Bll H Gl Gl 60 73''n-Bll H MOE I~IOE 102 ::
. .
.`
:;~

- ~ . " . ". .,, .; , , .~.. '; . - ,. - . .

~28~2 TABLE I I I ( continuation l ~

0 5 I I l _ Ex IR, I R ~ R R' M.p.( C) 74 n-Bu Cl Bn ~ n-Pent 76 n-Bu H CH~ AAE 81 77 n-Bu H CH3 AAP
78 n-Bu H Bn AAP
79 n-Bu H Bn AAE
n-Bu H Bn APE
81 n-Bu H Bn AAHE
82 n-Bu H Bn AAMHE
84 n-Bu H Bn W-Et n-Bu H Bn Z-CH-Et2 86 n-Bu H Bn Z-c-Pent n-Bu H BnZ-CH~-c-Pent 91 n-Bu H BnZ-c Hex 92 n-Bu I I BnZ-t-Bu 93 n-Bu H BnY-t-Bu .
94 n-Bu H BnY-n-Pent n-Bu H BnDeae 96 n-Bu H BnCH(CH3)-n-Bu 97 n-Bu H BnCH(CH~)-CO-E
2 0 98 n-Bu H CH3CH.-~:O-Et 100 : .~ 99 n-Bu H BnCH2-CO-Et 100 n-Bu II Bn X-Et 101 n-Bu H Bn~V-n-Pent _ 102 n-Bu H Bn EPh 103 - n-Bu H Bn Ph 104 n-Bu H Bn Mcs :~ 105 n-Bu H Bnn-Dec 106 n-Bu 11 Bnn-Hep 107 n-Bu 1-1 Bni-Pent 108 n-Bu H Bn . i-Pr 109 n-Bu H Bn CH~-c-Pr : ~ 110 n-Bu H Bn i-Bu 111 n-BIl H Bn n-Cet 11~ n-Bu I-I Bn n-Bu 113 n-BIl II Et Et 114 n-BIl }1 Cl13 n-Pent . l lS n-PI I I Bn n-Pent . ~ 11~ n-Bu lI Bn Z-n-Pent _ n-Bll 11 Bn t-Bu ; 35 :::~ - : :. , : , ,:
,. " ., ::.: . . , .

~9~8~2 TABLE III ( continuation 2 ) Ex Rl R, ¦ R R' M.p.( 120n-Bu H Bn Et 121n-Bu H CH3 Z-n-Pent 122n-Bu H Bn n-Pent 123n-Bu H Bn Z-CH2-c-Hex 124n-Bu H n-Pent Bn 125n-Bu H CH3 Bn 126 n-Bu H Et Bn . -127 n-Bu H n-Bu Bn 128 n-Bu H n-Cet Bn 129 n-Bu H i- Bu Bn 130 n-Bu H -CH.-c-Pr Bn 131 n-Bu H i-Pcnt Bn 134 n-Bu H H AAP 140 135 n-Bu H H AAE 168 136 n-Bu H H APE 13S
137n-Bll l~ H AAHE 108 138 n-Bu H 1~ AAMHE 110 139 n-Bu H H Z-CH-Et2 170 140 n-Bu H H Z-c-Pent 170 141 n-Bu II H W-Et 15S
144n-:l~u H H Z-CH,-c-Pent 154 145 n-Bu H H Z-c-Hex 60 146n-l~ll H H Z-t-Bu 90 147n- Bu H H Y-t-Bu 160 . 148 n-Bu H H Y-n-Pent 140 149 n-Bu H H Y-n-Pr 162 150 n-Bu H H Deae 68 ;:: 25 151 n-Bu H H CH(CH3)-n-Bu 74 ~, 152 n-Bu II H CH (CH3)-CO-Et 80 .~ 153 n-Bu H H X-Et 164 154 n-Bu 11 H ~V-n-Pent 157 155n-Bll H H CH.-CO-Et 144 .: 156 n-Bu II H EPh 128 157 n-Bu H 1-l Ph 231 158n-Bll H H Mcs 78 lS9 n-Bu ll n-Dec S0 :~

~ . , . , ~ . . .

.: , - :: . : : . .: , .,.:., . . : . , :;

: ~, : , ~
:~ . : ; .: . , :.

~2~ g~

TABLE I I I ( end ) l R ~ - R' M.p.( C) 160 n-Bu H H n-Hep 96 161 n-Bu H H i-Pent 164 162 n-Bu H H i-Pr l72 163 n-Bu H H CH2-c-Pr 171 164 n-Bu H H i-Bu 163 165 n-Bu H H n-Cet 82 166 n-Bu H H n-Bu lSl 167 n-Pr H H n-Pent 177 168 n-Bu H H Z-n-Pent 143 169 n-Bu H H Et 173 170 n-Bu H H n-Pent 161 171 n-Bu H H Z-CH,-c-Hex 114 172 n-Bu H n-Pent k 202 173 n-Bu H CH3 H 188 171 n-Bu H Et H 201 175 n-Bu H n-Bu H 194 176 n-Bu H n-Cet H 152 177 n-Bu H i-Bu H 190 178 n-Bu H CH,-c-Pr H 198 179 n-Bu H i-Pent H 197 181 n-Bu H AAP AAP 97 182- n-Bu H Pz Pz 250-260 184 n-Bu H Bn Y-n-Pr 18; n-Bu H Y-n-Pr Y-n-Pr 186 n-Bu H CH3 W-Et 196 n-Bu H Bn H 17S
213-- n-Bu H H Deae 206 2s214 n-Bu II n-Pent n-Pent ~4 n-Bu Cl H n-Pent 145 _ Notes: *: 3 HCI
;: **: 3 HO.C-CO~H
". ***: 2HCI
~ 30 :

3s f :- : . : ., ~ . -,, ~ . ~ .. . : . . .

2~2~2 TABLE IV

05 N~

R ~ ~ ~ NH~3 `
~ R"' R~ ~ ~/

Ex R~ R,I R~ R~ ¦ M.p.( C) n-Bu ClI TT CO CH3 185 31 n-Bu ClI CO.CH3 ~T 182 Sl n-Bu Cl TT CO2H 158 j2 n-Bu ClCO,H TT 200 56 n-Bu Cl C~ Co2CH3 126 57 n-Bu ClCO,CH3 CN
j8 n-Bu Cl TTT CO~CH3 59 n-Bu ClCO,CH3 TTT 130 n-Bu H TSA CO2CH3 135 61 n-Bu Cl TSA CO CH3 244 66 n-Bu Cl TSA CO H 234 67 n-B~ H TSA CO2H 190 88 n-Bu HCO,CH3 CONH-AAE 42 89 n-BIl HCO;CH3 CONHOCH3 146 132 n-Bu H 4-CN CO2-n-Pent 142 n-Bu H CO.H CO-L,Val-OEt 110 143 n-Bu H CO2H . CO-Gly-OEt 140 187 n-Bu H TSA CO2-Y-n-Pr 228 188 n-Bu H OCSA CO2CH3 125 189 n-Bu H MCSA Co2CH3 145 190 n-Bu H PCSA CO2CH3 220 Il-~U H PllSA CO2CH3 120 192 n-Bu H PASA CO2CH3 228 193 n-Bu H MESA CO2CH3 120 194 n-Bu H OCSA CO2-n-Pent 259 -I

` .. ' . ; ,. ~: - ` . - . . : :, . : . ~.; ;. ':

~ ~ ~ 2 ~ r~ 2 - 7~ -TABLE IV ( end ) ~5 ~ ~ ' n. ¦ R" M.p.( C) 201 n-Bll H ¦ .~ICSA CO2H 235 202 n-Bu I I PCSA CO,H 215 ; 203 n-Bll H PllSA CO2H 203 204 n-Bll H PASA CO2H 193 205 n-Bll H .~lESA CO2H . 238 : 206 n-BIl H CO.I-ICONH(CH )3N(CH3)2 111 207 n-Bu H CO;H CO~-AAE 92 208 n-Bll H CO;H CONnH-O-CH3 211 209- n-BIl 11 CO;H CO~nH2 196 210 n-Bll H CO;H CONnI(n-Bu) 183 211 n-Bu H OCSA CO2H 198 215 n-Bu 1~ CO.CH3CONnH(CH2)3N(CH3)2 2I6'' n-Bu H CO;CH3CONlH(CH.)3N(CH3)2 164 217 n-Bll H TTT CO2-n Pent 2I8~ n-Bll H TT CO2-n-Pent 204 219 n-Bll 11 CO.C1-13 CONH2 186 : 220 n- Bu 11 CO; C1~3 CONH(n-Bu) 125 221 n-Bll 11 CO;-Bn CO-I,-Val-OEt 222 n-BIl H CO;-Bn CO-Gly-OEt 107 : 227 n-Bu H OASA CO CH3 150(dec) 22~ n-Bu H OASA C~2H 150(dec) .; .. _ _ . .
;: ~ote :~ HCl~ fum~l.lte ;

2 ~

TABLE V

N ~ \~=( R Jl \\
~ I \ N / N ~,~
'-; 10 ` ~ O OR
~: 0~
, 1 ` OR
~' 15 ~' -'3 .:
PrepR, R R M.p.( C) 11 n-Bll Cl CH, CH CH, 136 12 n-Bu H CH, CH CH, 86 33 n-Bu H H H 28û
: ~ 25 3J n-Bu ~ 11 268 ;:
:~ `
:`

~, .~ : :: ` , , -:, ~ : , . , : ` - :, . . . .
,:, ` .. : .: : .. , :, .:` :: . , ~` -::`: ;`
:.. : : :: : : :: - : . : : ` ` : . : . .

2~2~2 TABLE VI

R, ~ , N

OR

.

Prep R, i R~ ¦ R ¦ R' ] ~.p.( C) : 20 16 n-Bu Cl CH, CH, 47 n-Bu Cl H H 221 ~, :

:`!
.

i''' .
~ 30 , : 35 - 81 - 2~928~2 TABLE VI I

05 ' n Bu ~~ R4 `' 10 RO 1~ ~ CR' o E.Y R ¦ R' ¦ R~ M.p.( C) _ 72- Pz Pz 4-N O. 194 83 CH3 n-Pent 6-CI
87 CH3 n-Pcllt 6-CH3 117 t-Bu CH3 4-NO.
133 t-Bu n-Pellt 4-NO;
180 AAE AAE 4-NO; 158 183 Y-t-Bu Y-t-Bu 4-NO2 83 197 H n-Pent 4-NO2 161 ~3 H n-Pent 6-CH3 153 Note: * 31~CI

.~

;~
`' ~92g~2 The products according to the invention are inhibitors of the effects of angiotensin II.
The activity of the compounds according to the invention as angiotensin II vascular receptor anta-05 gonists was evaluated by their efficacy in antagonizingthe contractile response induced by angiotensin II in isolated rabbit aorta rings. The rings are suspended in a bath of Krebs-Henseleit maintained at 37 C and aerated with an O2/CO2 mixture (95/5; v/v), and are -10 then stretched to a rest tension of 2 g. After one hour at rest, a contraction is caused with angiotensin II (3-10-9 M) in the presence of the test product pre-~incubated for 15 minutes. The concentration (expressed ;in nanomol) of test product which produces a 50% inhi-bition of the contractile response (IC50) is calculated from the concentration-response curve. The results obtained with a number of compounds according to the invention are collated in Table VIII.
The products according to the invention are useful in therapeutics in the treatment or prevention of arterial hypertension, glaucoma, circulatory dis-orders, restenosis due to angioplasty, developments of atheromatous or fibrinoproliferative lesions, nephro-pathy and retinopathy of diabetic origin, infarctus and angor and for improvement of the cognitive function.
According to the invention, a therapeutic com-position is recommended which contains at least one 'compound of formula I or one of its addition salts in a therapeutically effective amount in association with a physiologically acceptable excipient.
It is also recommended to use the compounds of formula I or one of their addition salts as angiotensin iII antagonists in order to obtain a drug for the pre-vention or cure of arterial hypertension, circulatory disorders and glaucoma.
. :

,:

~v~2$~2 TABLE VI I I

_ Ex ICso (~10-9 ~ _ Ex ICso (xlO-9 32 3.6 158 75 33 7,1 161 64 lo 34 8.4 163 50 1.2 164 40 39 I06.2 168 67 57.6 170 80 41 5.1 174 80 42 ~.1 178 67 ~3 6.3 180 30 44 5.3 181 80 6.7 183 60 46 lO.S 187 7 ~7 71.3 195 82 48 5.3 197 5;
49 13.2 198 4.6 j.7 ?01 10 ~1 10.8 202 14.7 52 40.2 203 4.4 iS 69.1 204 9.5 66 8.~ 205 5.5 67 1.3 ~09 70 68 30 210 ~4 76 - 90 211 0.8 141 10 2?6 6 " 155 ~5.~
.~ _ :, . .

.

~.
i - ~ . , ` ' ' ' : ;: : i.' ` '' ' ' ' ': ~' ` `' ` :' ` ' ., ~ : :` . '

Claims

1. A phenylaminomethylimidazole compound which is selected from the group consisting of:
(i) the phenylaminomethylimidazoles of the formula (I) in which:
- R1 is a C1-C4-alkyl group;
- R2 is the hydrogen atom, a halogen, a C1-C4-alkylthio group or a C1-C3-perfluoroalkyl group;
- R3 is the hydrogen atom, a C1-C4-alkyl group or a group COR8, in which R8 is a C1-C4-alkyl group;
- R4 is in the 3-, 4-, 5- or 6-position and is the hydrogen atom, one or more C1-C4-alkyl, C1-C4-alkoxy, azido or nitro groups or one or more halogens, or forms a 2-aminonaphthyl group with the aminophenyl group to which it is bonded;
- R5 is a hydrogen atom or a halogen; and - R6 and R7, which are identical or different, are each a tetrazol-5-yl group or a group COR9, in which R9 is:
- a hydroxyl group, - a C1-C16-alkoxy group, - a cyclopropylmethoxy group, - a phenoxy group, - a benzyloxy group, - a 2-phenylethoxy group, - a glyceryl group, - an isopropylideneglyceryl group, - a 2-methoxyethoxy group, - a 2-oxobutoxy group, - a 1-methyl-2-oxobutoxy group, - a 2-(N,N-diethylamino)ethoxy group, - a morpholinoethoxy group, - an N-(ethoxy)nicotinamide group, - a group O-CHR15-O(CO)-R12, in which R15 is the hydrogen atom or a C1-C3-alkyl group and R12 is a C1-C7-alkyl group, a cyclopentyl group, a cyclohexyl group, a cyclopentylmethyl group or a cyclohexylmethyl group, - an oxyacetate group of the formula O-CHR17-CO2-R16, in which R16 and R17 are each independently the hydrogen atom or a C1-C5 -alkyl group, - an oxyacetamide group of the formula O-CH2-CO-NR10R11, in which R10 and R11, which are identical or different, are each a C1-C4-alkyl group or a hy-droxyethyl group or form a 4-methylpiperazin-1-yl group with the nitrogen atom to which they are bonded, or - an amino group of the formula -NR18R19, in which R18 and R19 are each independently the hydrogen atom, a C1-C4-alkyl group, a methoxy group or a 2-(N,N-dimethylamino)propyl group, or -NR18R19 is an amino acid residue of the glycine or valine structure in which the acid group is optionally protected in the form of an ester or amide;
- it also being possible for R6 to be:
- a group COR13, in which R13 is a methylsul-fonylamino group of the formula -NH-SO2-CH, or an aryl-sulfonylamino group of the formula in which R14 is the hydrogen atom, a halogen, an azido group, a C1-C4-alkyl group or a methoxy group and can be located in the ortho-, meta- or para-position; and - it being possible for R3 and R7 taken together to form, with the nitrogen atom and the phenyl group to which they are respectively bonded, a 2-carboxyindol-1-yl or 2-ethoxycarbonylindol-1-yl ortho-fused nitrogen-containing heterocycle; and (ii) the addition salts of the compounds of formula I
with mineral and organic acids or with mineral and organic bases.

2. A compound according to claim 1 wherein, in formula I, R6 or R7 is a group COOH.

3. A compound according to claim 2 wherein the carboxyl groups R6 and R7 are salified with an organic or mineral base.

4. A compound of formula I according to claim 1 which is salified with an organic or mineral acid.

5. A compound according to claim 1 wherein, in formula I; R6 or R7 is a methylsulfonylaminocarbonyl group or an arylsulfonylaminocarbonyl group.

6. A therapeutic composition which contains at least one compound of formula I or one of its addition salts in a therapeutically effective amount in associa-tion with a physiologically acceptable excipient.

7. Use of a compound according to claim 1 as an angiotensin II antagonist in order to obtain a drug for the prevention or cure of arterial hypertension, cir-culatory disorders or glaucoma.

8. An intermediate useful in the synthesis of com-pounds of formula I according to claim 1, which is a 1-phenylmethylimidazole-5-carboxaldehyde product of the formula in which:
(i) R'1 is an n-propyl group, R'2 is a hydrogen atom or a halogen, R'5 is the hydrogen atom and R'6 is a cyano group or a group COR'9 in which R'9 is a C1-C16-alkoxy group or a benzyloxy group, or (ii) R'2 is an n-butyl group, R'2 and R'5 are the hydrogen atom and R'6 is a group COR'9 in which R'9 is a t-butoxy or benzyloxy group.

9. An intermediate useful in the synthesis of com-pounds of formula I according to claim 1, which is a 1-phenylmethyl-5-hydroxymethylimidazole product of the formula in which:

R'1 is a C1-C4-alkyl group, R'2 is the hydroqen atom or a halogen, R'5 is the hydrogen atom and R'6 is a group COR'9 in which R'9 is a C1-C16-alkoxy group or a benzyloxy group.

10. An intermediate useful in the synthesis of com-pounds of formula I according to claim 1, which is a 1-phenylmethyl-5-halogenomethylimidazole product of the formula in which:
R'1 is an n-butyl group, R'2 and R'5 are the hydrogen atom, R'6 is a group COR'9 in which R'9 is a t-butoxy or benzyloxy group, and X is a halogen.