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W Schunack

Publications and source records attributed to W Schunack.

At least 163 records · Page 9Linked to original sources
PubMed1988

[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.

Animals↗
PubMed1988

[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.

Animals↗
PubMed1988

[Alkyl- and alkoxy-substituted lamtidine analogs: synthesis and H2-antagonistic activity. 38. H2-antihistaminics].

In studies on the structure-activity relationships of histamine H2-receptor antagonists, lamtidine analogous derivatives of ortho-, meta- und para-substituted piperidinomethylphenoxypropylamines bearing an additional substituent on the aromatic ring were prepared and tested for their H2-antagonistic activity on the isolated guinea-pig atrium. An additional substituent decreases the H2-antagonistic activity of the 3-(3-piperidinomethyl-phenoxy)-propylamine derivatives, while 2-membered substituents neighboring the connecting chain increase the activity of the ortho- and para-piperidinomethyl-substituted phenoxypropylamine derivatives.

Animals↗
PubMed1987

What are the differences between the H2-receptor antagonists?

The H2-receptor antagonists which are used for ulcer therapy fall into four main structural classes. Cimetidine is an imidazole derivative; ranitidine belongs to the basically substituted furans, famotidine is a member of the guanidinothiazole group; and roxatidine belongs to the aminoalkylphenoxy series. Famotidine is the most potent, selective H2-receptor antagonist yet available for ulcer therapy. On a weight basis, famotidine is approximately eight times more potent than ranitidine and 40 times more potent than cimetidine. Cimetidine, ranitidine and famotidine are competitive antagonists, while the long-acting H2-receptor antagonists, e.g. loxtidine and lamitidine, are insurmountable H2-receptor blockers. Famotidine has a longer duration of action than either ranitidine or cimetidine. Because famotidine does not interact with cytochrome P-450 of the hepatic enzyme system, it does not appear to affect the metabolism of drugs metabolized by this system. The overall number of side-effects of the H2-receptor antagonists is in the range of 2-3% and no irreversible adverse effects are known. Famotidine has been found to be generally well tolerated. In a first post-marketing study, the number of patients with side-effects was only 0.43%. Side-effects such as headache, dizziness, constipation and diarrhoea have been observed only occasionally. Thus, famotidine is a safe and potent H2-receptor blocker of acid secretion.

Histamine H2 Antagonists↗
PubMed1986

[Tetrahydroisoquinolines as components of H2-antagonists. 27. H2-antihistaminics].

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.

Animals↗
PubMed1986

[Synthesis and H2-antagonistic action of N3, N5-substituted 1,2, 4-oxadiazole-3, 5-diamine. 26. H2-antihistaminics].

N5-(3-[3-(1-Piperidinylmethyl)phenoxy) phenoxy]propyl)-1,2, 4-oxadiazole-3, 5-diamines and N5(2-[(5-dimethylaminomethyl-2-furanyl) methylthio] ethyl)-1,2,4-oxadiazole-3,5-diamines with different N3-substituents were prepared and tested for their H2-antihistaminic activity on the isolated guinea-pig atrium. They were synthesized by nucleophilic substitution of the appropriate 5-trichloromethyloxadiazoles with the amines 3 and 11. Of the prepared substances 10a,c in particular showed high H2-antagonistic activity.

Animals↗
PubMed1986

[Synthesis and H2-antagonistic action of N,N-substituted 1,3,4-oxadiazole-2,5-diamine. 30. H2-antihistaminics].

The semicarbazides 1 and 5a-c were transformed in high yields into the biureas 3a, b and the thiobiureas 10a-c and 11a-c by addition to appropriate iso(thio)cyanates and subsequently cyclisized to the N,N'-substituted 1,3,4-oxadiazole-2,5-diamines by means of elimination of water or hydrogen sulphide. The synthesized compounds were tested for H2-antagonistic activity at the isolated spontaneously beating guinea-pig atrium, where especially 4a, b and 12c showed pronounced H2-antagonistic action.

Animals↗
PubMed1985

Stereoselectivity of the histamine H3-presynaptic autoreceptor.

The effects of the enantiomers of two chiral analogues of histamine (alpha, N alpha-dimethylhistamine and N alpha-methyl-alpha-chloromethylhistamine) were studied at H3-autoreceptors modulating histamine release in rat brain slices. These compounds act as H3-receptor agonists, displaying a low potency relative to histamine (below 4%) but a pronounced stereoselectivity (ratio of 31 for the isomers of alpha, N alpha-dimethylhistamine and 183 for their halogenated analogues) was observed. The (+)isomers (corresponding to S-configurated L-histidine) were highly preferred at H3-receptors, whereas the (-)isomers were more potent at H2-receptors, no difference being observed at H1-receptors. In addition, no such stereoselectivity was observed for the two isomers of a chiral impromidine derivative: both Sopromidine and its S enantiomer acted as antagonists of histamine at H3-autoreceptors with similar potencies (Ki = 5.6 X 10(-8) M and 4.5 X 10(-8) M), whereas Sopromidine acted as an H2-receptor agonist and the S-enantiomer as an H2-receptor antagonist. Our results indicate that H3-autoreceptors are chemically stereoselective, with structural requirements different from those of H1- and H2-receptors.

Animals↗