Novel thieno[2,3-b]- and [3,4-b]pyrans as potassium channel openers. Thiophene systems—XVII

The syntheses and antihypertensive activity of the thieno3,4-b]pyran and thieno2,3-b]pyran isosteres of the potassium channel opener (PCO) RWJ 26629 (± 2a) are reported. While the unsubstituted thiophene derivatives were active at 20 mg/kg, introduction of a strong electron withdrawing group in the 2-position of the thieno3,2-b] series increased potency. Similar substitution on the thieno3,4-b] series significantly lowered potency. Compounds 26 and 30 are approximately 5-fold more potent than the prototypic PCO cromakalim (± 1).