Potential antisecretory antidiarrheals. 1. Alpha 2-adrenergic aromatic aminoguanidine hydrazones.
Guanabenz, a centrally acting antihypertensive agent, has been shown to have intestinal antisecretory properties. A series of aromatic aminoguanidine hydrazones was made in an effort to separate the antisecretory and cardiovascular activities. Benzaldehyde, naphthaldehyde, and tetralone derivatives were synthesized. The compounds were evaluated in the cholera toxin treated ligated jejunum of the rat and in the Ussing chamber using a rabbit ileum preparation. A number of compounds, including members of each structural class, were active upon subcutaneous administration in the rat. Active compounds were determined to be alpha 2-adrenergic agonists by yohimbine reversals of their Ussing chamber activities. The compound displaying the best separation of activities was the aminoguanidine hydrazone of 2,6-dimethyl-4-hydroxybenzaldehyde (20).
D000316:Adrenergic alpha-Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000930:Antidiarrheals / Q000138:chemical synthesis*; D002772:Cholera Toxin / Q000633:toxicity; D005260:Female; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology; D006835:Hydrazones / Q000138:chemical synthesis* / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship
D000316:Adrenergic alpha-Agonists; D000930:Antidiarrheals; D006146:Guanidines; D006835:Hydrazones; D007202:Indicators and Reagents; D002772:Cholera Toxin