US 4,045,563 AGranted

Substituted 2-[pyridylalkylenesulfinyl]-benzimidazoles with gastric acid secretion inhibiting effects

AssigneeAB Hassle

InventorsPeder Bernhard Berntsson, Stig Ake Ingemar Carlsson, Lars Erik Garberg, Ulf Krister Junggren, Sven Erik Sjostrand, Gunhild Wika VON Wittken Sundell

Life of this patent

Estimating the term…

Abstract

Compounds having the structural formula ##STR1## PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME, AND THE USE THEREOF FOR AFFECTING GASTRIC ACID SECRETION; INTERMEDIATE PRODUCTS HAVING THE STRUCTURAL FORMULA ##STR2## AND METHODS FOR PREPARING THE SAME.

Claims65

Dependent claims

A compound of formula I ##STR12## or a therapeutically acceptable salt thereof in which R is selected from the group consisting of hydrogen, alkyl having up to four carbon atoms, halogen of the group consisting of fluoro, iodo, bromo and chloro, cyano, carboxy, carboxyalkyl in which the alkyl group has up to 4 carbon atoms, carboalkoxy in which the alkyl group has up to 4 carbon atoms, carboalkoxyalkyl wherein each of the alkyl groups has up to 4 carbon atoms, carbamoyl, carbamoylalkyl in which the alkyl group has up to 4 carbon atoms, hydroxy, alkoxy having up to 5 carbon atoms, hydroxyalkyl having up to 7 carbon atoms, trifluoromethyl and alkanoyl having up to 4 carbon atoms in any position;

R.sup.3 is selected from the group consisting of hydrogen, alkyl having up to four carbon atoms, halogen of the group consisting of fluoro, iodo, bromo and chloro, carboxy, carboxyalkyl in which the alkyl group has up to 4 carbon atoms, carboalkoxy in which the alkyl group has up to 4 carbon atoms, carboalkoxyalkyl wherein each of the alkyl groups has up to 4 carbon atoms, carbamoyl, carbamoylalkyl in which the alkyl group has up to 4 carbon atoms, hydroxy, alkoxy having up to 5 carbon atoms, hydroxyalkyl having up to 7 carbon atoms, trifluoromethyl and alkanoyl having up to 4 carbon atoms in any position;
R.sup.4 is selected from the group consisting of hydrogen, alkyl straight or branched chain having up to 5 carbon atoms, alkanoyl having up to 4 carbon atoms, carbamoyl, alkylcarbamoyl wherein the alkyl group may be straight or branched and has up to 4 carbon atoms, dialkylcarbamoyl wherein each alkyl group has up to 4 carbon atoms, alkylcarbonylmethyl wherein the alkyl group has up to 4 carbon atoms, alkoxycarbonylmethyl wherein the alkyl group has up to 4 carbon atoms, and alkylsulphonyl wherein the alkyl group has up to 4 carbon atoms;
R.sup.6 is a straight or branched alkyl group having 1 to 4 carbon atoms, wherein at most one methylene group is present between S and Het, and Het is pyridyl, which may be further substituted preferably in the 3 to 5 position with lower alkyl groups such as methyl, ethyl or propyl or with halogen substituents such as chloro and bromo.

A compound selected from the group consisting of:

2-[2-pyridylmethylsulfinyl]benzimidazole,
2-[2-pyridylmethylsulfinyl]-(4,6dimethyl)benzimidazole
2-[2-pyridylmethylsulfinyl]-(5-ethyl)benzimidazole,
2-pyridylmethylsulfinyl]-(4-methyl, 6-chloro)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(5-methoxy)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(5-hydroxy)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(5-acetyl)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(5-carboxy)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(5-carbethoxy)benzimidazole,
2-[2-(4-chloro)pyridyl-methylsulfinyl]benzimidazole),
2-[2-(5-methyl)pyridylmethylsulfinyl]benzimidazole,
2-[2-pyridylmethylsulfinyl]-N-methylbenzimidazole),
2-[2pyridyl-(methyl)methylsulfinyl]benzimidazole,
2-[2-pyridylmethylsulfinyl]-(4-methyl)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(N-acetyl)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(N-methoxycarbonyl)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(5methyl)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(5-chloro)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(5-isopropyl)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(5-t-butyl)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(5-n-propyl)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(N-carbamoyl)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(N-methylcarbamoyl)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(N-acetylmethyl)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(N-ethoxycarbonylmethyl)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(N-methylsulfonyl)benzimidazole,
2-[2(4-methyl)pyridylmethylsulfinyl]-(5-methyl)benzimidazole,
2-[2-(5-methyl)pyridylmethylsulfinyl]-(5-methyl)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(6-chloro)benzimidazole,
2-[2-pyridyl-(ethyl)methylsulfinyl]benzimidazole,
2-[2-pyridyl-(ethyl)methylsulfinyl]-(5-chloro)benzimidazole,
2-[2-pyridyl-(methyl)methylsulfinyl]-5-ethyl)benzimidazole,
2-[2-(3-methyl)pyridylmethylsulfinyl]benzimidazole,
2-[2-(5-ethyl)pyridylmethylsulfinyl]-(5-methyl)benzimidazole,
2-[2-(5-ethyl)pyridylmethylsulfinyl]benzimidazole,
2-[2pyridyl-(ethyl)methylsulfinyl]-(5-ethyl)benzimidazole,
2-[2-pyridyl-(methyl)methylsulfinyl]-(5-methyl)benzimidazole,
2-[2-pyridyl-(methyl)methylsulfinyl]-(5-cyano)benzimidazole,
2[2pyridyl-(methyl)methylsulfinyl]-(5-trifluoro)benzimidazole,
2-[2-pyridyl-(ethyl)methylsulfinyl]-5-methyl)benzimidazole,
2-[2-pyridyl-(ethyl)methylsulfinyl]-(5-cyano)benzimidazole,
2-[2-pyridyl-(ethyl)methylsulfinyl]-(5-trifluoro)benzimidazole,
2-[2-pyridylmethylsulfinyl]-(4-chloro)benzimidazole,
2-[2-pyridyl-(isopropyl)methylsulfinyl]benzimidazole,
2-[2-pyridyl-(methyl)methylsulfinyl]-(5,6-dimethyl)benzimidazole, and
2-[2-pyridylmethylsulfinyl]-(5,6-dimethyl)benzimidazole,
and a therapeutically acceptable salt thereof.

44 more elements

A method of inhibiting gastric acid secretion by administering to mammals, including man, suffering from gastric acid secretion disturbances a compound of the formula I ##STR13## or a therapeutically acceptable salt thereof in which R is selected from the group consisting of hydrogen, alkyl having up to four carbon atoms, halogen of the group consisting of fluoro, iodo, bromo and chloro, cyano, carboxy, carboxyalkyl in which the alkyl group has up to 4 carbon atoms, carboalkoxy in which the alkyl group has up to 4 carbon atoms, carboalkoxyalkyl wherein each of the alkyl groups has up to 4 carbon atoms, carbamoyl, carbamoylalkyl in which the alkyl group has up to 4 carbon atoms, hydroxy, alkoxy having up to 5 carbon atoms, hydroxyalkyl having up to 7 carbon atoms, trifluoromethyl and alkanoyl having up to 4 carbon atoms in any position;

R.sup.3 is selected from the group consisting of hydrogen, alkyl having up to four carbon atoms, halogen of the group consisting of fluoro, iodo, bromo and chloro, carboxy, carboxyalkyl in which the alkyl group has up to 4 carbon atoms, carboalkoxy in which the alkyl group has up to 4 carbon atoms, carboalkoxyalkyl wherein each of the alkyl groups has up to 4 carbon atoms, carbamoyl, carbamoylalkyl in which the alkyl group has up to 4 carbon atoms, hydroxy, alkoxy having up to 5 carbon atoms, hydroxyalkyl having up to 7 carbon atoms, trifluoromethyl and alkanoyl having up to 4 carbon atoms in any position;
R.sup.4 is selected from the group consisting of hydrogen, alkyl straight or branched chain having up to 5 carbon atoms, alkanoyl having up to 4 carbon atoms, carboalkoxy wherein the alkyl group has up to 4 carbon atoms, carbamoyl, alkylcarbamoyl wherein the alkyl group may be straight or branched and has up to 4 carbon atoms, dialkylcarbamoyl wherein each alkyl group has up to 4 carbon atoms, alkyl carbonylmethyl wherein the alkyl group has up to 4 carbon atoms, alkoxycarbonylmethyl wherein the alkyl group has up to 4 carbon atoms, and alkylsulphonyl wherein the alkyl group has up to 4 carbon atoms;
R.sup.6 is a straight or branched alkyl group having 1 to 4 carbon atoms, wherein at most one methylene group is present between S and Het, and Het is pyridyl, which may be further substituted preferably in the 3 to 5 position which lower alkyl groups such as methyl, ethyl and propyl or with halo substituents such as chloro and bromo, in amount sufficient to inhibit such suffering.

A pharmaceutical composition for inhibiting gastric acid secretion, characterized in that it contains as active agent 0.1 to 95% by weight of a compound of formula I ##STR14## or a therapeutically acceptable non-toxic acid addition salt thereof in a therapeutically effective amount to inhibit gastric acid secretion, in which R selected from the group consisting of hydrogen, alkyl having up to four carbon atoms, halogen of the group consisting of fluoro, iodo, bromo and chloro, cyano, carboxy, carboxyalkyl in which the alkyl group has up to 4 carbon atoms, carboalkoxy in which the alkyl group has up to 4 carbon atoms, carboalkoxyalkyl wherein each of the alkyl groups has up to 4 carbon atoms, carbamoyl, carbamoylalkyl in which the alkyl group has up to 4 carbon atoms, hydroxy, alkoxy having up to 5 carbon atoms, hydroxyalkyl having up to 7 carbon atoms, trifluoromethyl and alkanoyl having up to 4 carbon atoms in any position;

R.sup.3 is selected from the group consisting of hydrogen, alkyl having up to four carbon atoms, halogen of the group consisting of fluoro, iodo, bromo and chloro, carboxy, carboxyalkyl in which the alkyl group has up to 4 carbon atoms, carboalkoxy in which the alkyl group has up to 4 carbon atoms, carboalkoxyalkyl wherein each of the alkyl groups has up to 4 carbon atoms, carbamoyl, carbamoylalkyl in which the alkyl group has up to 4 carbon atoms, hydroxy, alkoxy having up to 5 carbon atoms, hydroxyalkyl having up to 7 carbon atoms, trifluoromethyl and alkanoyl having up to 4 carbon atoms in any position;
R.sup.4 is selected from the group consisting of hydrogen alkyl straight or branched chain having up to 5 carbon atoms, alkanoyl having up to 4 carbon atoms, carbamoyl, alkylcarbamoyl wherein the alkyl group may be straight or branched and has up to 4 carbon atoms, dialkylcarbamoyl wherein each alkyl group has up to 4 carbon atoms, alkylcarbonylmethyl wherein the alkyl group has up to 4 carbon atoms, alkoxycarbonylmethyl wherein the alkyl group has up to 4 carbon atoms, and alkylsulphonyl wherein the alkyl group has up to 4 carbon atoms;
R.sup.6 is a straight branched alkyl group having 1 to 4 carbon atoms, whereby at most one methylene group is present between S and Het, and Het is pyridyl, which may be further substituted preferably in the 3 to 5 position with substituents selected from the group consisting of methyl, ethyl, propyl, chloro and bromo, together with a pharmaceutically acceptable carrier.

Dependencies are inferred from the claim text.

Facts

Application: 05/630,916Filed 11 Nov 1975
Granted: 30 Aug 1977
Term ends: Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07D 235/28
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 417/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links

Family

No related US applications are recorded in the indexed filing history.

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

Abstract

R.sup.3 is selected from the group consisting of hydrogen, alkyl having up to four carbon atoms, halogen of the group consisting of fluoro, iodo, bromo and chloro, carboxy, carboxyalkyl in which the alkyl group has up to 4 carbon atoms, carboalkoxy in which the alkyl group has up to 4 carbon atoms, carboalkoxyalkyl wherein each of the alkyl groups has up to 4 carbon atoms, carbamoyl, carbamoylalkyl in which the alkyl group has up to 4 carbon atoms, hydroxy, alkoxy having up to 5 carbon atoms, hydroxyalkyl having up to 7 carbon atoms, trifluoromethyl and alkanoyl having up to 4 carbon atoms in any position;
R.sup.4 is selected from the group consisting of hydrogen, alkyl straight or branched chain having up to 5 carbon atoms, alkanoyl having up to 4 carbon atoms, carbamoyl, alkylcarbamoyl wherein the alkyl group may be straight or branched and has up to 4 carbon atoms, dialkylcarbamoyl wherein each alkyl group has up to 4 carbon atoms, alkylcarbonylmethyl wherein the alkyl group has up to 4 carbon atoms, alkoxycarbonylmethyl wherein the alkyl group has up to 4 carbon atoms, and alkylsulphonyl wherein the alkyl group has up to 4 carbon atoms;
R.sup.6 is a straight or branched alkyl group having 1 to 4 carbon atoms, wherein at most one methylene group is present between S and Het, and Het is pyridyl, which may be further substituted preferably in the 3 to 5 position with lower alkyl groups such as methyl, ethyl or propyl or with halogen substituents such as chloro and bromo.

Facts

Application

05/630,916Filed 11 Nov 1975

Granted

30 Aug 1977

Term ends

Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07D 235/28
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 417/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links