title: New bronchodilators. Synthesis and bronchodilating activity of some 3-(alkoxymethyl)-alpha-(N-substituted aminomethyl)-4-hydroxybenzyl alcohols.
abstract: A series of 3-(alkoxymethyl)-alpha-(N-substituted aminomethyl)-4-hydroxybenzyl alcohols was synthesized as potential bronchodilators. The ability to prevent effects against histamine-induced bronchoconstriction in guinea pigs was studied to determine their bronchodilating activity. Introduction of a methoxymethyl group in place of the m-hydroxyl group of beta-adrenergic catecholamines afforded compounds especially effective in delaying histamine-induced bronchoconstriction in guinea pigs. Appropriate N-substitution also enhanced the potency of these catecholamine analogues. 4-Hydroxy-3-(methoxymethyl)-alpha-[N-[4-(methoxymethyl)-alpha-methylphenyl]aminoethyl]benzyl alcohol hemifumarate (3r) was the most potent compound in this series.
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001592:Benzyl Alcohols / Q000138:chemical synthesis* / Q000494:pharmacology; D001593:Benzyl Compounds / Q000138:chemical synthesis*; D001993:Bronchodilator Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D001592:Benzyl Alcohols; D001593:Benzyl Compounds; D001993:Bronchodilator Agents; D006632:Histamine