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

J B Press; J J McNally; P J Sanfilippo; M F Addo; D Loughney; E Giardino; L B Katz; R Falotico; B J Haertlein

doi:10.1016/s0968-0896(00)82153-7

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

Bioorg Med Chem. 1993 Dec;1(6):423-35. doi: 10.1016/s0968-0896(00)82153-7.

Authors

J B Press¹, J J McNally, P J Sanfilippo, M F Addo, D Loughney, E Giardino, L B Katz, R Falotico, B J Haertlein

Affiliation

¹ R.W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776.

PMID: 8087564
DOI: 10.1016/s0968-0896(00)82153-7

Abstract

The syntheses and antihypertensive activity of the thieno[3,4-b]pyran and thieno[2,3-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 thieno[3,2-b] series increased potency. Similar substitution on the thieno[3,4-b] series significantly lowered potency. Compounds 26 and 30 are approximately 5-fold more potent than the prototypic PCO cromakalim (+/- 1).

MeSH terms

Animals
Antihypertensive Agents / chemical synthesis
Antihypertensive Agents / chemistry
Antihypertensive Agents / pharmacology
Aorta / drug effects
Benzopyrans / pharmacology
Cromakalim
Drug Evaluation, Preclinical
Glyburide / pharmacology
Hypertension / drug therapy
In Vitro Techniques
Models, Molecular
Molecular Structure
Potassium Channels / drug effects*
Pyrroles / pharmacology
Rats
Rats, Inbred SHR
Structure-Activity Relationship
Thiophenes / chemical synthesis
Thiophenes / chemistry
Thiophenes / pharmacology*

Substances

Antihypertensive Agents
Benzopyrans
Potassium Channels
Pyrroles
Thiophenes
Cromakalim
Glyburide