It is well known that both histamine and dimaprit show moderate histamine H2-receptor agonistic activities on the guinea pig right atrium. Quantum chemical calculations on these two compounds showed similarities in electron distributions and molecular electrostatic potentials (MEP's), which could be extended to rigid analogues [2-amino-5-(2-aminoethyl)thiazoles] of the latter structure. On the base of these results a series of substituted 4- and 5-(2-aminoethyl)thiazoles was synthesized applying small alkyl substitution variations as reported for histamine. 2-Amino-5-(2-aminoethyl)-4-methylthiazole (Amthamine) proved to be the most potent full histamine H2-receptor agonist on the guinea pig right atrium, being with a pD2 value of 6.21 slightly more potent than histamine. This compound shows no affinity for H1-receptors and is a full but weak agonist on the histamine H3-receptor with a pD2 value of 4.70, thus showing a marked specificity for histamine H2-receptors. In the 5-(2-aminoethyl)thiazole series the presence of a 2-amino substituent proved to be not essential for stimulation of the histamine H2-receptor, leading to the important conclusion that in contrast to histamine, for this series, acceptance of a proton by the thiazole nucleus of the agonist from the active site of the receptor is sufficient for the stimulation of the histamine H2-receptor.

No abstract

The N'-(4-1H-imidazol-4-ylphenyl)formamidines were recently introduced as a new class of active H2 antagonists; the authors of the compounds (Donetti et al. of de Angeli, Italy) have suggested that these compounds interact with the H2 receptor through their monocations. This is at variance with the model proposed for cimetidine by the SK&F (Smith Kline & French, UK) group who proposed the neutral molecule as the species active at the H2 receptor. In the present study we have investigated the issue whether the neutral or charged species is the active one by measuring the pA2 values of mifentidine and cimetidine at different pH values. Changing the pH will influence the species equilibria of both compounds and thereby affect their activity. The activity changes measured for both compounds are consistent with the proposition that cimetidine as well as mifentidine elicit their activity through their neutral species.

Olefinierung der Hydroxybenzaldehyde (II) mit dem Wittig‐ Reagenz (I) ergibt die Hydroxybenzyliden‐phthalide (III), die beim Erhitzen mit.

Die Indandione (Ia) und (Ib) werden mit.