Relaxant activity of 4-amido-3,4-dihydro-2H-1-benzopyran-3-ols and 4-amido-2H-1-benzopyrans on guinea pig isolated trachealis

• Published in: Journal of medicinal chemistry Vol. 33; no. 11; pp. 3028 - 3034
• Main Authors: Buckle, Derek R, Arch, Jonathon R. S, Fenwick, Ashley E, Houge-Frydrych, Catherine S. V, Pinto, Ivan L, Smith, David G, Taylor, Stephen G, Tedder, John M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01-11-1990
• Subjects: 4-amido-2H-1-benzopyran; Amides - chemical synthesis; Amides - chemistry; Amides - pharmacology; Animals; Benzopyrans - chemical synthesis; Benzopyrans - chemistry; Benzopyrans - pharmacology; Bronchodilator Agents - chemical synthesis; Bronchodilator Agents - chemistry; Bronchodilator Agents - pharmacology; Chemical Phenomena; Chemistry; Cromakalim; Guinea Pigs; Molecular Structure; Muscle Relaxation - drug effects; potassium; Potassium Channels - drug effects; Potassium Channels - physiology; Pyrroles - chemistry; Pyrroles - pharmacology; Structure-Activity Relationship; Trachea - physiology
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00173a019

A series of 4-amido-3,4-dihydro-2H-1-benzopyran-3-ols and 4-amido-2H-1-benzopyrans related to the potassium channel activator cromakalim have been prepared and evaluated for their relaxant activity in guinea pig isolated tracheal spirals. Several analogues show enhanced relaxant activity relative to cromakalim in this preparation and the rank order of potency for those substituents investigated at C-6 was CF3 greater than CN greater than C2H5 greater than aza greater than or equal to CH3. One compound, trans-3,4-dihydro-2,2-dimethyl-4-(2-oxopiperidin-1-yl)-7-(trifluor omethyl)-2H- 1-benzopyran-3-ol (24), was resolved into its two enantiomers and the activity was shown to reside essentially in the (+)-isomer, adding further support to the suggestion that the smooth muscle receptor for these potassium channel activators is stereoselective.