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und einigen Synthesis of (Z)-and (E)-3-(1H-imidazol-4-yl)-2-propenamine3-(1H-Imidazol-4-yl)propanamine (6, homohistamine), an essential intermediate for the synthesis of potent impromidinetype histamine H, receptor agonists, is efficiently prepared from trans-urocanic acid (1) by reduction of the methyl ester 2 and conversion to the saturated amide 4. Dehydration with thionyl chloride yields the nitrile 5 which is subsequently reduced to 6. Side-chain methylated 3-(1H-imidazol-4-yl)propanamines 12 are available from 1H-imidazole-4-carbaldehyde (7) and 1-( 1H-imidazol-4-y1)ethanone (a), respectively, via unsat-
The cimetidine-like moiety of the potent H2-agonist impromidine (9a) and three closely related guanidines (10a, 11a, and 12a) which are modified in the imidazolylpropyl portion, has been replaced by 2-[(2-pyridyl)methylthio]ethyl, 2-(benzylthio)ethyl and 3,3-diphenylpropyl substituents. Guanidines 10-12 were obtained from acidic hydrolysis of corresponding N-benzoyl guanidines 7, 8, and 15, accessible by successive aminolysis of diphenyl N-benzoyl carbonimidate (2) according to known methods. Compared with leads 10a and 11a lipophilic substitution affords almost equipotent H2-agonists 10b-d and 11b-d, while substituents with increasing lipophilicity enhance both intrinsic activity and potency of the weak partial agonist 12a at guinea-pig atrial H2-receptors. Guanidines 10-12 are weak H1-antagonists on the isolated guinea-pig ileum.
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Histamine Analogues: Imidazolylalkylguanidines.Synthesis and in vitro Pharmacology.-Title compounds like (IV) and (VII) (10 examples) show weak H1-antagonistic activity on guinea pig ileum but good H2-agonistic activity on isolated guinea pig right atrium. (IVa) and (IVb) are more potent H2-agonists than histamine.-(SELLIER, C.; ELZ, S.; BUSCHAUER, A.; SCHUNACK, W.; Eur.
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