Claims for Patent: 4,024,271

Summary for Patent: 4,024,271

Title:	Pharmacologically active guanidine compounds
Abstract:	The compounds are substituted thioalkyl-, aminoalkyl- and oxyalkyl-guanidines which are inhibitors of histamine activity.
Inventor(s):	Durant; Graham John (Welwyn Garden City, EN), Emmett; John Colin (Codicote, EN), Ganellin; Charon Robin (Welwyn Garden City, EN)
Assignee:	Smith Kline & French Laboratories Limited (Welwyn Garden City, EN)
Application Number:	05/637,499
Patent Claims:	1. A method of inhibiting H-2 histamine receptors 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: ##STR15## wherein A is such that there is formed together with the carbon atom shown an unsaturated heterocyclic nucleus, said unsaturated heterocyclic nucleus being an imidazole, pyrazole, pyrimidine, pyrazine or pyridazine ring; X.sub.1 is hydrogen, lower alkyl, hydroxyl, trifluoromethyl, benzyl, halogen, amino or ##STR16## in which E' is NH or N-cyano; X.sub.2 is hydrogen or when X.sub.1 is lower alkyl, lower alkyl or halogen; k is 0 to 2 and m is 2 or 3, provided that the sum of k and m is 3 or 4; Y is oxygen, sulphur or NH; E is NR.sub.2 ; R.sub.1 is hydrogen, lower alkyl or di-lower alkylamino-lower alkyl; and R.sub.2 is hydrogen, nitro or cyano, or a pharmaceutically acceptable addition salt thereof with the proviso that X.sub.1 is ##STR17## only when E is NH or N-cyano. 2. A method of claim 1 in which the heterocyclic compound is N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)-methylthio)ethyl]guanidin e or a pharmaceutically acceptable addition salt thereof. 3. A method of claim 2 in which the heterocyclic compound is N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)-methylthio)ethyl]guanidin e in the form of its free base. 4. A method of claim 3 in which the heterocyclic compound is administered orally. 5. A method of claim 3 in which the heterocyclic compound is administered in a daily dosage regimen of from about 150 mg. to about 1000 mg. 6. A method of inhibiting gastric acid secretion which comprises administering 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: ##STR18## wherein A is such that there is formed together with the carbon atom shown an unsaturated heterocyclic nucleus, said unsaturated heterocyclic nucleus being an imidazole, pyrazole, pyrimidine, pyrazine or pyridazine ring; X.sub.1 is hydrogen, lower alkyl, hydroxyl, trifluoromethyl, benzyl, halogen, amino or ##STR19## in which E' is NH or N-cyano; X.sub.2 is hydrogen or when X.sub.1 is lower alkyl, lower alkyl or halogen; k is 0 to 2 and m is 2 or 3, provided that the sum of k and m is 3 or 4; Y is oxygen, sulphur or NH; E is NR.sub.2 ; R.sub.1 is hydrogen, lower alkyl or di-lower alkylamino-lower alkyl; and R.sub.2 is hydrogen, nitro or cyano, or a pharmaceutically acceptable addition salt thereof with the proviso that X.sub.1 is ##STR20## only when E is NH or N-cyano. 7. A method of claim 6 in which the heterocyclic compound is N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)-methylthio)ethyl]guanidin e or a pharmaceutically acceptable addition salt thereof. 8. A method of claim 7 in which the heterocyclic compound is N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)-methylthio)ethyl]guanidin e in the form of its free base. 9. A pharmaceutical composition to inhibit H-2 histamine receptors comprising a pharmaceutical carrier and in an effective amount to inhibit said receptors a heterocyclic compound of the formula: ##STR21## wherein A is such that there is formed together with the carbon atom shown an unsaturated heterocyclic nucleus, said unsaturated heterocyclic nucleus being an imidazole, pyrazole, pyrimidine, pyrazine or pyridazine ring; X.sub.1 is hydrogen, lower alkyl, hydroxyl, trifluoromethyl, benzyl, halogen, amino or ##STR22## in which E' is NH or N-cyano; X.sub.2 is hydrogen or when X.sub.1 is lower alkyl, lower alkyl or halogen; k is 0 to 2 and m is 2 or 3, provided that the sum of k and m is 3 or 4; Y is oxygen, sulphur or NH; E is NR.sub.2 ; R.sub.1 is hydrogen, lower alkyl or di-lower alkylamino-lower alkyl; and R.sub.2 is hydrogen, nitro or cyano, or a pharmaceutically acceptable addition salt thereof with the proviso that X.sub.1 is ##STR23## only when E is NH or N-cyano. 10. A pharmaceutical composition of claim 9 in which the heterocyclic compound is N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)methylthio)ethyl]guanidine or a pharmaceutically acceptable addition salt thereof. 11. A pharmaceutical composition of claim 10 in which the heterocyclic compound is N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)methylthio)ethyl]guanidine in the form of its free base. 12. A pharmaceutical composition of claim 11 in which the pharmaceutical composition is in the form of a tablet or capsule. 13. A pharmaceutical composition of claim 11 in which the heterocyclic compound is present in an amount of from about 50 mg. to about 250 mg.