New tetrahydronaphthalene derivatives as combined thromboxane receptor antagonists and thromboxane synthase inhibitors.
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.
Cimetière
B
B
Institut de Recherches Servier, Centre de Recherches de Croissy, Croissy-sur-Seine, France.
Dubuffet
T
T
Landras
C
C
Descombes
J J
JJ
Simonet
S
S
Verbeuren
T J
TJ
Lavielle
G
G
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000037:antagonists & inhibitors; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011312:Pressure; D011817:Rabbits; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors* / Q000097:blood; D014132:Trachea / Q000187:drug effects / Q000502:physiology
C117573:2-(4-chlorophenylsulfonamido)-6-propyl-7-((pyridin-3-yl)methyl)-1,2,3,4-tetrahydronaphthalene-5-propanoic acid; D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013764:Tetrahydronaphthalenes; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D013930:Thromboxane-A Synthase