Darstellung und H2-agonistische Aktivität alkylsubstituierter 3-(Imidazol-4-yl)propylguanidine

Synthesis and H2-agonistic activity of alkylsubstituted 3-(imidazole-4-yl) propylguanidine

[H2-antagonistic activity of the impromidine analog, cyanoguanidine. 37. H2 antihistaminics]

In studies on structure-activity relationships among impromidine-like histamine H2-receptor agonists, the synthesis of impromidine analogous guanidines led to the corresponding intermediate cyanoguanidines. The latter are structurally related to cimetidine. For that reason they were tested for H2-antagonistic activity on the isolated guinea-pig atrium. Compound 5h proved to be significantly more potent than cimetidine. Derivatives with branched thioether moiety were devoid of affinity. The results are consistent with existing structure-activity relationships

Impromidin-analoge Guanidine: Synthese und Wirkung am Histamin-H2-Rezeptor. 29. Mitteilung: Histamin-Analoga

Impromidine-analogous guanidines: synthesis and activity at the histamine H2-receptor. 29. Histamine analogs. / 19 impromidine analogous guanidines were synthetized by acid hydrolysis of the corresponding N-cyanoguanidines. The guanidines were tested on the isolated spontaneously beating guinea-pig atrium for histamine H2-receptor affinity. Lengthening the ethyl chain of cysteamine by one methylene group leads to partial agonists of decreased activity. Impromidine congeners containing a branched cimetidine side chain prove to be potent H2-agonists with maximal or near maximal response. Affinity ratios in favour of the (R)-configurated enantiomers are moderate but clearly significant. The interaction between the affinity contributing moiety and the complementary receptor area shows a lower degree of stereoselectivity than does the efficacy contributing (imidazole-4-yl)propyl substituent of impromidine and sopromidine, respectively. Homoisohistamine derivatives dramatically lose both efficacy and affinity

Histamine analogues. 36th communication. Basically substituted histamine derivatives with H1-agonistic activity

Piperidinoalkyl-, morpholinoalkyl- or [(pyrid-2-yl)methylthio]alkyl-substituents were introduced into position 2 of the essential histamine structure. These 2-substituted histamine derivatives were prepared via reaction of imidate hydrochlorides in liquid ammonia under pressure with 1,3-dihydroxypropanone followed by a stepwise build-up of the side chain in position 4 of the imidazole nucleus (route I) or by cyclization with 2-oxo-4-phthalimido-1-butyl acetate (route II) followed by deprotection of the primary amine function. The novel compounds were screened for H1-activity on the isolated guinea-pig ileum and for H2-activity on the isolated guinea-pig right atrium. While 10a, c-e proved to be weak partial H1-agonists, 10b, f were very weak H1-antagonists

Side-chain modified analogues of histaprodifen: Asymmetric synthesis and histamine H₁-receptor activity

New analogues of histaprodifen with polar side chains have been stereoselectively synthesized and evaluated as histamine H₁-receptor agonists. As a key transformation the asymmetric aminohydroxylation has been used, which was successfully realized for the first time on an imidazolyl derivative. While all chiral analogues proved to be weak H₁-receptor antagonists, an achiral keto derivative of histaprodifen turned out to be the first 2-acylated histamine congener displaying partial H₁-receptor agonism (relative potency 12%)

Chinazolinone, 1. Mitt. Darstellung, Kristallstruktur und Wirkung von 2-Methyl-3(4-oxo-3-phenyl-thiazolidin-2-ylidenamino)-4-(3H)-chinazolin on

Quinazolinones. 1. Preparation, crystal structure and action of 2-methyl-3-(4-oxo-3-phenyl-thiazolidine-2-ylidenamino)-4-(3H)- quinazolinone