Abstract
We discovered a novel series of 3,4-dihydro-2H-benzo[1,4]oxazin-8-yloxyacetic acid derivatives as potent dual-acting agents to block the TXA2 receptor and to activate the PGI2 receptor. We report the synthesis, structure-activity relationship, and in vitro, ex vivo, and in vivo pharmacology of this series of compounds. 4-[2-(1,1-Diphenylethylsulfanyl)ethyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-yloxyacetic acid N-methyl-D-glucamine salt (7) is a promising candidate for a novel treatment in the anti-thrombotic and the cardiovascular fields avoiding hypotensive side effects.
MeSH terms
-
Animals
-
Benzoxazines / chemical synthesis
-
Benzoxazines / chemistry*
-
Benzoxazines / pharmacology*
-
Blood Platelets / chemistry
-
Blood Platelets / metabolism
-
Cell Membrane / chemistry
-
Cell Membrane / metabolism
-
Cells, Cultured
-
Drug Evaluation, Preclinical
-
Drug Synergism
-
Fibrinolytic Agents / chemical synthesis
-
Fibrinolytic Agents / chemistry
-
Fibrinolytic Agents / pharmacology
-
Humans
-
Macaca fascicularis
-
Male
-
Molecular Structure
-
Receptors, Epoprostenol / agonists*
-
Receptors, Thromboxane A2, Prostaglandin H2 / antagonists & inhibitors*
-
Structure-Activity Relationship
Substances
-
Benzoxazines
-
Fibrinolytic Agents
-
Receptors, Epoprostenol
-
Receptors, Thromboxane A2, Prostaglandin H2