Details for Patent: 4,287,198

Title:	Pharmacologically active guanidine compounds
Abstract:	The compounds are substituted thioalkyl-, aminoalkyl- and oxyalkyl-guanidines which are inhibitors of histarine activity.
Inventor(s):	Durant; Graham J. (Welwyn Garden City, GB2), Emmett; John C. (Codicote, GB2), Ganellin; Charon R. (Welwyn Garden City, GB2)
Assignee:	Smith Kline & French Laboratories Limited (Welwyn Garden City, GB2)
Filing Date:	Mar 03, 1980
Application Number:	06/126,809
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: ##STR16## wherein A is such that there is formed together with the carbon atom shown an unsaturated heterocyclic nucleus, said unsaturated heterocyclic nucleus being a 3-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridine) ring; X.sub.1 is hydrogen, lower alkyl, hydroxyl, trifluoromethyl, benzyl, halogen, amino or ##STR17## 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. 2. A method of claim 1 in which the heterocyclic compound is administered orally. 3. A method of claim 1 in which the heterocyclic compound is administered in a daily dosage regimen of from about 150 mg. to about 1000 mg. 4. A method of inhibiting gastric acid secretion which comprises administering to an animal in need thereof 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 a 3-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridine) ring; X.sub.1 is hydrogen, lower alkyl, hydroxyl, trifluoromethyl, benzyl, halogen, amino or ##STR19## 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. 5. 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: ##STR20## wherein A is such that there is formed together with the carbon atom shown an unsaturated heterocyclic nucleus, said unsaturated heterocyclic nucleus being a 3-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridine ring; X.sub.1 is hydrogen, lower alkyl, hydroxyl, trifluoromethyl, benzyl, halogen, amino or ##STR21## 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. 6. A pharmaceutical composition of claim 5 in which the heterocyclic compound is N-cyano-N'-methyl-N"-[2-(3-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridyl)methyl thio)ethyl]guanidine. 7. A pharmaceutical composition of claim 5 in which the pharmaceutical composition is in the form of a tablet or capsule. 8. A pharmaceutical composition of claim 5 in which the heterocyclic compound is present in an amount of from about 50 mg. to about 250 mg. 9. A method of claim 1 in which the heterocyclic compound is N-cyano-N'-methyl-N"-[2-(3-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridyl)methyl thio)ethyl]guanidine.