# US 4,399,142 A · Pharmacologically active compounds

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- Number: US 4,399,142 A
- Document ID: US4399142A
- Status: Granted
- Kind: A
- Application number: 06/364,134
- Filed: 1982-03-31
- Granted: 1983-08-16
- Earliest claimed: 1973-05-03
- Assignees: Smith Kline & French Laboratories Limited
- Inventors: Graham J. Durant; John C. Emmett; Charon R. Ganellin
- Web page: https://patentgrep.com/patent/US4399142A

## CPC

- C07D 239/56: One oxygen atom and one sulfur atom
- C07D 233/86: Oxygen and sulfur atoms, e.g. thiohydantoin
- C07D 233/88: Nitrogen atoms, e.g. allantoin
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Heterocyclic compounds which are inhibitors of histamine activity, in particular, inhibitors of H-2 histamine receptors. A specific compound of this invention is 2-[2-(4-methyl-5-imidazolymethylthio)ethylamino]-4-pyrimidone.

## Claims

### Claim 1

A method of inhibiting H-2 histamine receptors, said H-2 histamine receptors being those histamine receptors which are not inhibited by mepyramine but are inhibited by burimamide, which comprises administering to an animal in need of inhibition of said receptors in an effective amount to inhibit said receptors a heterocyclic compound of the formula: ##STR4## wherein A taken together with the nitrogen and carbon atoms shown forms a quinazoline or quinoline ring, said ring having a keto, thione or sulfone group and optionally substituted by one or two lower alkyl, phenyl or benzyl groups; R is a grouping of the formula:
Het--CH.sub.2 Z(CH.sub.2).sub.n --
wherein Het is a nitrogen containing heterocyclic ring selected from imidazole, thiazole, isothiazole or thiadiazole, said ring being optionally substituted by lower alkyl, amino, hydroxy or halogen; Z is sulphur or a methylene group and n is 2 or 3 or a pharmaceutically acceptable acid addition salt thereof.

### Claim 2 (depends on 1)

A method of claim 1 in which the heterocyclic compound is administered in a daily dosage of from about 150 mg. to about 750 mg.

### Claim 3

A method of inhibiting gastric acid secretion which comprises administering internally to an animal in need of inhibition of gastric acid secretion in an effective amount to inhibit gastric acid secretion a heterocyclic compound of the formula: ##STR5## wherein A taken together with the nitrogen and carbon atoms shown forms a quinazoline or quinoline ring, said ring having a keto, thione or sulfone group and optionally substituted by one or two lower alkyl, phenyl or benzyl groups; R is a grouping of the formula:
Het--CH.sub.2 Z(CH.sub.2).sub.n --
wherein Het is a nitrogen containing heterocyclic ring selected from imidazole, thiazole, isothiazole or thiadiazole, said ring being optionally substituted by lower alkyl, amino, hydroxy or halogen; Z is sulphur or a methylene group and n is 2 or 3 or a pharmaceutically acceptable acid addition salt thereof.

### Claim 4

A pharmaceutical composition to inhibit H-2 histamine receptors, said H-2 histamine receptors being those histamine receptors which are not inhibited by mepyramine but are inhibited by burimamide, comprising a pharmaceutical carrier and in an effective amount to inhibit said receptors a heterocyclic compound of the formula: ##STR6## wherein A taken together with the nitrogen and carbon atoms shown forms a quinozoline or quinoline ring, said ring having a keto, thione or sulfone group and optionally substituted by one or two lower alkyl, phenyl or benzyl groups; R is a grouping of the formula:
Het--CH.sub.2 Z(CH.sub.2).sub.n --
wherein Het is a nitrogen containing heterocyclic ring selected from imidazole, thiazole, isothiazole or thiadiazole, said ring being optionally substituted by lower alkyl, amino, hydroxy or halogen; Z is sulphur or a methylene group and n is 2 or 3 or a pharmaceutically acceptable acid addition salt thereof.

### Claim 5 (depends on 4)

A pharmaceutical composition of claim 4 in which the heterocyclic compound is present in an amount of from about 50 mg. to about 250 mg.