ABSTRACT
In studies on structure-activity relationships of histamine H2-receptor antagonists, lamtidine-analogue derivatives of N-(3-hydroxyphenyl)guanidine and 5- and 7-hydroxy-tetrahydroisoquinoline were prepared and tested for their H2-antagonistic activity on the isolated guinea-pig atrium and on the histamine-stimulated acid secretion of the anaesthetized rat. A further aim of the investigations was to examine the influence of a lengthening of the side-chain as well as the substitution of the aminotriazole with other H2-antagonistic components, on the pharmacological data of the above-mentioned isoquinoline derivatives. All compounds made showed only little H2-antagonistic activity on the guinea-pig atrium. At the acid secretion a noticeable activity especially of the 7-hydroxy-tetrahydroisoquinoline isomers could be observed.
Subject(s)
Histamine H2 Antagonists/chemical synthesis , Isoquinolines/chemical synthesis , Animals , Chemical Phenomena , Chemistry , Gastric Acid/metabolism , Guinea Pigs , Heart/drug effects , Ileum/drug effects , In Vitro Techniques , Isoquinolines/pharmacology , Male , Muscle, Smooth/drug effects , Rats , Rats, Inbred StrainsABSTRACT
In studies on structure-activity relationships of histamine H2-receptor antagonists, C-2 basically substituted thiazoles were prepared and tested for their H2-antihistaminic activity on the isolated guinea-pig atrium and on the histamine stimulated acid secretion of the anaesthetized rat. As a basic substituent the dimethylaminomethyl group is especially suitable, while cyclic guanidines lead to lower H2-antagonistic activity.
Subject(s)
Histamine H2 Antagonists/chemical synthesis , Thiazoles/chemical synthesis , Animals , Chemical Phenomena , Chemistry , Electric Stimulation , Gastric Acid/metabolism , Guinea Pigs , Histamine H2 Antagonists/analysis , Histamine H2 Antagonists/pharmacology , In Vitro Techniques , Magnetic Resonance Spectroscopy , Male , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Rats , Rats, Inbred Strains , Thiazoles/analysis , Thiazoles/pharmacologyABSTRACT
In studies on H2-antihistaminics, guanidinothiazoles were prepared and tested for their H2-antihistaminic activity on the isolated guinea-pig atrium. Whereas the N,N'-disubstituted cyanoguanidines 3 and 5 possess stronger H2-activity than tiotidine, the 5-substituted 4-pyrimidinones 7a, b proved to be as effective as the reference substance.
