[Thiazolylalkylamines: synthesis of analogs of imidazolylethylamines and their effect on gastric secretion].
As a part of a study on H2-agonists, the preparations and properties are reported for a representative group of 2-aminothiazolethylamine derivatives which contain the gastric secretion stimulating S-aminoalkylisothiourea moiety. The test compounds were obtained by known methods or from 2-(2-amino-5-thiazolyl)ethyl chloride and were tested for their possible histamine-like activities on different biological substrates. From the biological results it appears that the behaviour of the substances is rather complex, but the following general observations can be pointed out: the contracturant properties, sometimes quite marked, do not derive from direct H1-specific activities; the effects, particularly evident in stimulating in vitro or in vivo gastric secretion, in relaxing gall-bladder smooth muscle, on auriculae and/or on blood pressure, are not competitively antagonized by cimetidine; none of the tested compounds proved to be an antagonist of histamine H2-receptors, while one of them is found to inhibit competitively the H1-receptors. On the basis of structure-activity relationships it can be excluded that the iuxta-nuclear NH2 group of 2-aminothiazolethylamines reacts, in some way, with the H2-receptors, since, in this case, the 2-aminothiazole group is not a pharmacophore like the 2-aminoimidazole or isothiurea group. Consequently the hypotheses, that the flexibility of the molecule is a fundamental requirement for the H2-stimulating properties of S-(3-dimethylaminopropyl)isothiurea and that the different activities of 2-aminohistamine, in comparison with those of 2-methylhistamine, are due to the existence of a hydrophilic area suitable for the allocation of the iuxta-nuclear NH2 group in the H2-receptor, are strengthened.
D000588:Amines / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis*; D001667:Binding, Competitive / Q000187:drug effects; D002415:Cats; D055598:Chemical Phenomena; D002621:Chemistry; D005753:Gastric Mucosa / Q000187:drug effects; D006168:Guinea Pigs; D006635:Histamine H2 Antagonists; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000588:Amines; D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D013844:Thiazoles
Tiazolilalchilamine: sintesi di congeneri delle imidazoliletilamine e loro attività nella secrezione gastrica.