Novel thieno[2,3-b]- and [3,4-b]pyrans as potassium channel openers. Thiophene systems--XVII.
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).
Press
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JB
R.W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776.
McNally
J J
JJ
Sanfilippo
P J
PJ
Addo
M F
MF
Loughney
D
D
Giardino
E
E
Katz
L B
LB
Falotico
R
R
Haertlein
B J
BJ
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004353:Drug Evaluation, Preclinical; D005905:Glyburide / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy; D066298:In Vitro Techniques; D008958:Models, Molecular; D015394:Molecular Structure; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D013876:Thiophenes; D019806:Cromakalim; D005905:Glyburide