[(Aminomethyl)aryloxy]acetic acid esters. A new class of high-ceiling diuretics. 1. Effects of nitrogen and aromatic nuclear substitution.
A series of Mannich bases and aminomethyl derivatives of ethyl [2,3-dichloro-4-(4-hydroxybenzoyl)phenoxy]acetate were synthesized and tested for saluretic and diuretic activities. The effects of nitrogen and aromatic nuclear substitution, reorientation of the aminomethyl group relative to that of the phenolic hydroxyl group, and replacement of either the phenolic hydroxyl or the aminomethyl group by other functional groups are described. Ethyl [2,3-dichloro-4-[3-(aminomethyl)-4-hydroxybenzoyl]phenoxy]acetate (27) was found to be a very potent, high-ceiling diuretic.
D000284:Administration, Oral; D000818:Animals; D001681:Biological Assay; D001794:Blood Pressure / Q000187:drug effects; D004232:Diuretics / Q000138:chemical synthesis*; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006016:Glycolates / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D007202:Indicators and Reagents; D008252:Macaca fascicularis; D008297:Male; D008744:Methylamines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012964:Sodium / Q000652:urine; D013329:Structure-Activity Relationship
D004232:Diuretics; D006016:Glycolates; D007202:Indicators and Reagents; D008744:Methylamines; D005665:Furosemide; D012964:Sodium