1.
Bioorg Med Chem Lett
; 8(11): 1375-80, 1998 Jun 02.
Article
in English
| MEDLINE
| ID: mdl-9871769
ABSTRACT
New polysubstituted tetrahydronaphthalene derivatives were prepared as thromboxane receptor (TP-receptor) antagonists. Within this series of compounds S 18886 has been identified as an orally active, highly potent antagonist with a very long duration of action in different species.
Subject(s)
Receptors, Thromboxane/antagonists & inhibitors , Sulfonamides/chemical synthesis , Sulfonamides/pharmacology , Tetrahydronaphthalenes/chemical synthesis , Tetrahydronaphthalenes/pharmacology , Animals , Guinea Pigs , Humans , In Vitro Techniques , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Platelet Aggregation Inhibitors/chemical synthesis , Platelet Aggregation Inhibitors/pharmacology , Pressure , Rabbits , Stereoisomerism , Structure-Activity Relationship , Trachea/drug effects , Trachea/physiology
2.
Bioorg Med Chem Lett
; 8(11): 1381-6, 1998 Jun 02.
Article
in English
| MEDLINE
| ID: mdl-9871770
ABSTRACT
A pyridine group was linked to the tetrahydronaphthalene moiety of the derivatives described in the preceding paper, to afford new combined thromboxane receptor (TP-receptor) antagonists and synthase inhibitors. The most interesting compound 2f inhibits TXA2 synthase with an IC50 value of 0.64 microM and the aggregation of human platelets with an IC50 value of 0.063 microM and shows a long duration of action in different species after oral administration.
