Quinuclidine chemistry. 4. Diuretic properties of cis-3-amino-2-benzhydrylquinuclidine.
A number of 3-amino-2-benzhydrylquinuclidines were tested for diuretic activity in both rats and dogs. The Schiff base formed from 2-benzhydryl-3-quinuclidinone and benzylamine was reduced with NaBH4 to a mixture of isomers, the cis isomer being preponderants. cis-2-Benzhydryl-3-benzylaminoquinuclidine was isolated by chromatography and debenzylat:d to cis-3-amino-2-benzhydrylquinuclidine, the most active compound in this series. The corresponding trans isomer was considerably less active. It was made by reacting the mesylate of cis-2-benzhydr-l-3-quinuclidinol with Nan3 to form trans-3-azido-2-benzhydrylquinuclidine which was reduced with LiAlH4. In dose-response studies (sodium excretion as a function of dose) in rats the maximal or ceiling effect of cis-3-amino-2-benzhydrylquinuclidine was considerably greater than that of hydroflumethiazide but less than that of furosemide. An unusual biphasic dose-response was seen in dogs with cis-3-amino-2-bezhydrylquinuclidine, centering around 10 mg/kg.
D000818:Animals; D001559:Benzhydryl Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D002712:Chlorides / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005665:Furosemide / Q000494:pharmacology; D006857:Hydroflumethiazide / Q000494:pharmacology; D011188:Potassium / Q000652:urine; D011812:Quinuclidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000652:urine; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001559:Benzhydryl Compounds; D002712:Chlorides; D004232:Diuretics; D011812:Quinuclidines; D006857:Hydroflumethiazide; D005665:Furosemide; D012964:Sodium; D011188:Potassium