Claims for Patent: 3,950,333

Summary for Patent: 3,950,333

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:	05/450,957
Patent Claims:	1. A compound of the formula: ##SPC10## 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, hydroxy, trifluoromethyl, benzyl, halogen, amino or ##EQU6## 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 ##EQU7## only when E is NH or N-cyano. 2. A compound of claim 1 wherein Y is oxygen or sulphur. 3. A compound of claim 1 wherein Y is NH. 4. A compound of claim 1 wherein said unsaturated heterocyclic nucleus is imidazole, pyrazole, pyrimidine pyrazine or pyridazine and R.sub.2 is hydrogen or nitro. 5. A compound of claim 4 wherein k is 1 and m is 2. 6. A compound of claim 1 wherein said unsaturated heterocyclic nucleus is imidazole. 7. A compound of claim 6 wherein X.sub.1 is hydrogen, methyl, bromo, hydroxyl or amino and X.sub.2 is hydrogen; Y is sulphur and R.sub.1 is methyl. 8. A compound of claim 1, said compound being N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)-methylthio)ethyl]guanidin e. 9. A compound of claim 1, said compound being 2-(4-imidazolylmethylthio)ethyleneguanidine sulphate. 10. A compound of claim 1, said compound being N-[2-((4-methyl-5-imidazolyl)methylthio)ethyl]-N'-nitroguanidine. 11. A compound of claim 1, said compound being N-cyano-N'-ethyl-N"-[2-((4-methyl-5-imidazolyl)-methylthio)ethyl]guanidine 12. A compound of claim 1, said compound being N-[2-((4-bromo-5-imidazolyl)methylthio)ethyl]-N'-cyano-N"-methylguanidine. 13. A compound of claim 1, said compound being N-cyano-N"-[2-((4-methyl-5-imidazolyl)methylthio)ethyl]guanidine. 14. A compound of claim 1, said compound being N-cyano-N'-[2-(4-imidazolylmethylthio)ethyl]-N"-methylguanidine. 15. A compound of claim 1, said compound being N-cyano-N'-[2-((4-methyl-5-imidazolyl)methylthio)-ethyl]-N"-propylguanidin e. 16. A compound of claim 1, said compound being N-cyano-N'-methyl-N"-[2-((1-methyl-2-imidazolyl)-methylthio)ethyl]guanidin e. 17. A compound of claim 1, said compound being N-cyano-N'-[2-(2-imidazolylmethylthio)ethyl]-N"-methylguanidine. 18. A compound of claim 1, said compound being N-cyano-N'-methyl-N"-[2-((5-trifluoromethyl-4-imidazolyl)methylthio)ethyl] guanidine. 19. A compound of claim 1, said compound being N-cyano-N'-[2-(4-imidazolylmethoxy)ethyl]-N"-methylguanidine. 20. A compound of claim 1 said compound being N-cyano-N'-methyl-N"-[2-(3-pyrazolylmethylthio)-ethyl]guanidine. 21. A compound of claim 1, said compound being N-cyano-N'-methyl-N"-[2-(2-pyrazinylmethylthio)ethyl]guanidine. 22. A compound of claim 1, said compound being N-cyano-N'-methyl-N"-[2-(3-pyridazinylmethylthio)ethyl]guanidine.