4-Benzyl- and 4-benzoyl-substituted imidazole derivatives and use as medicaments

A pharmaceutical composition of matter comprising an anti-ulcer, anti-hypertensive, diuretic, sedative, analgesic, anti-inflammatory or tranquilizing effective amount of a compound of the formula ##STR45## wherein R.sub.1, R.sub.2 and R.sub.3, which can be the same or different, are each hydrogen, chloro, bromo, fluoro, methyl, ethyl, methoxy, amino, hydroxy, or nitro;

• R.sub.4 is hydrogen or alkyl of 1 to 7 carbon atoms;
• --X-- is ##STR46## R.sub.5 is hydrogen, hydroxy, --OR.sub.6 --;
• and R.sub.6 is alkyl of 1 to 7 carbon atoms or aryl of 6 to 10 carbon atoms;
• or a pharmaceutically acceptable acid addition salt or mixture thereof;
• with the provisos that:
• (a) when R.sub.1, R.sub.2 and R.sub.3 are simultaneously hydrogen, then --X-- is other than ##STR47## or --CH.sub.2 --;
• and (b) when R.sub.1 is 2-methyl, R.sub.2 is 5-methyl, R.sub.3 is hydrogen and R.sub.4 is methyl, then --X-- is other than --CH.sub.2 --;
• in combination with a pharmaceutically acceptable inert carrier.

A method for treating a mammal exhibiting an ulcerous condition, which comprises administering to said mammal an anti-ulcer effective amount of a compound of the formula:

• ##STR48## wherein R.sub.1, R.sub.2 and R.sub.3, which can be the same or different, are each hydrogen, chloro, bromo, fluoro, methyl, ethyl, methoxy, amino, hydroxy or nitro;
• R.sub.4 is hydrogen or alkyl of 1 to 7 carbon atoms;
• --X-- is ##STR49## R.sub.5 is hydrogen, hydroxy or --OR.sub.6 ;
• and R.sub.6 is alkyl of 1 to 7 carbon atoms or aryl of 6 to 10 carbon atoms;
• or a non-toxic pharmaceutically acceptable acid addition salt thereof.

A method for treating a mammal exhibiting an ulcerous condition, which comprises administering to said mammal an anti-ulcer effective amount of a compound of formula:

• ##STR50## wherein R.sub.1, R.sub.2 and R.sub.3, which can be the same or different, are each hydrogen, chloro, bromo, fluoro, methyl, ethyl, methoxy, amino, hydroxy, or nitro;
• R.sub.4 is hydrogen or alkyl of 1 to 7 carbon atoms;
• --X-- is ##STR51## R.sub.5 is hydrogen, hydroxy or --OR.sub.6 ;
• and R.sub.6 is alkyl of 1 to 7 carbon atoms or aryl of 6 to 10 carbon atoms;
• or a pharmaceutically acceptable acid addition salt thereof;
• with the provisos that:
• (a) when R.sub.1, R.sub.2 and R.sub.3 are simultaneously hydrogen, then --X-- is other than ##STR52## or --CH.sub.2 --;
• and (b) when R.sub.1 is 2-methyl, R.sub.2 is 5-methyl, R.sub.3 is hydrogen and R.sub.4 is methyl, then --X-- is other than --CH.sub.2 --.

A process for the preparation of a compound of the formula ##STR53## wherein R.sub.1, R.sub.2 and R.sub.3, which can be the same or different, are each hydrogen, chloro, bromo, fluoro, methyl, ethyl, methoxy, amino, hydroxy or nitro;

• and R.sub.4 is hydrogen or alkyl of 1 to 7 carbon atoms;
• with the provisos that:
• (a) R.sub.1, R.sub.2 and R.sub.3 are not simultaneously hydrogen;
• and
• (b) when R.sub.1 is 2-methyl, R.sub.2 is 5-methyl and R.sub.3 is hydrogen, then R.sub.4 is other than methyl;
• which comprises reacting formamide with a compound of the formula ##STR54## wherein R.sub.1, R.sub.2 and R.sub.3 are defined as above and Q is a radical selected from the group consisting of ##STR55## wherein R.sub.4 is defined as above, Hal is halogen atom, and R is a substituted or unsubstituted alkyl, aralkyl or aryl group, provided that:
• (a) when Q is ##STR56## the reaction with formamide is followed by treatment of the intermediate product with acid;
• and
• (b) when Q is ##STR57## the reaction with formamide is followed by hydrogenation of the intermediate product.

A process for the preparation of a compound of the formula ##STR65## wherein R.sub.1, R.sub.2 and R.sub.3, which can be the same or different, are each hydrogen, chloro, bromo, fluoro, methyl, ethyl, methoxy, amino, hydroxy or nitro;

• and R.sub.4 is hydrogen or alkyl of 1 to 7 carbon atoms;
• with the provisos that:
• (a) R.sub.1, R.sub.2 and R.sub.3 are not simultaneously hydrogen;
• and
• (b) when R.sub.1 is 2-methyl, R.sub.2 is 5-methyl and R.sub.3 is hydrogen, then R.sub.4 is other than methyl;
• which comprises hydrolysis of the corresponding compound of the formula ##STR66## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are defined as above and R.sub.6 is alkyl of 1 to 7 carbon atoms or aryl of 6 to 10 carbon atoms, in an aqueous solution of an inorganic acid at elevated temperature.

A process for the preparation of a compound of the formula ##STR67## wherein R.sub.1, R.sub.2 and R.sub.3, which can be the same or different, are each hydrogen, chloro, bromo, fluoro, methyl, ethyl, methoxy, amino, hydroxy or nitro;

• and R.sub.4 is hydrogen or alkyl of 1 to 7 carbon atoms;
• with provisos that:
• (a) R.sub.1, R.sub.2 and R.sub.3 are not simultaneously hydrogen;
• and
• (b) when R.sub.1 is 2-methyl, R.sub.2 is 5-methyl and R.sub.3 is hydrogen, then R.sub.4 is other than methyl;
• which comprises hydrogenation of the corresponding compound selected from the group consisting of ##STR68## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are defined as above, R.sub.6 is alkyl of 1 to 7 carbon atoms or aryl of 6 to 10 carbon atoms and R.sub.12 is an aryl group, in the presence of a hydrogenation catalyst selected from the group consisting of platinum oxide, palladium-on-carbon and Raney nickel.

A process for the preparation of a compound of the formula ##STR69## wherein R.sub.1, R.sub.2 and R.sub.3, which can be the same or different, are each hydrogen, chloro, bromo, fluoro, methyl, ethyl, methoxy, amino, hydroxy or nitro;

• with the proviso that R.sub.1, R.sub.2 and R.sub.3 are not simultaneously hydrogen, which comprises reacting the corresponding compound of the formula ##STR70## wherein R.sub.1, R.sub.2 and R.sub.3 are defined as above;
• R.sub.8, R.sub.9, R.sub.10 and R.sub.11, which can be the same or different, are each hydrogen, hydroxy, halogen, amino, --O--alkyl of 1 to 7 carbon atoms, or ##STR71## wherein R.sub.6 is alkyl of 1 to 7 carbon atoms or aryl of 6 to 10 carbon atoms;
• or wherein R.sub.8 and R.sub.10 can be combined to form a keto group, or R.sub.9 and R.sub.11 can be combined to form a keto group, or both R.sub.8 and R.sub.10 and R.sub.9 and R.sub.11 can simultaneously form keto groups;
• with a reagent selected from the group consisting of HN.dbd.CH--NH.sub.2 ;
• ##STR72## formamide;
• and a source of ammonia and formaldehyde.