Thromboxane A2 receptor antagonists

Molecular pharmacology and therapeutic potential of thromboxane A2 receptor antagonists, 25, 173... 

Antiplatelet and antithrombotic drugs Aspirin, dipyridamole, ticlopidine Thromboxane A2 receptor antagonists—vapiprost and solutroban... 

Thromboxane A2 receptor antagonists consisting of 2-decarboxy-2-phosphinico prostaglandins (V), and prostamide derivatives, (VI), prepared by deLong (4) and Krauss (5), respectively, and were used in glaucoma therapy. 

On the basis of these results it has been suggested that electronic factors— Hammett s sigma (a) constant, dipole moment (/z) and Swain and Lupton s polarity (F)—are crucial for the antithrombotic activity of these compounds. Interestingly, in all the active compounds presented in Fig. 24 the arrangement of substituents around the thiazole skeleton is different from one another. This has further widened the scope of this skeleton in the exploration of potential platelet aggregation inhibitors and thromboxane A2 receptor antagonist. 

Gresele P, Dedomyn H, Amout J, N nci GG, V rmyl n J. Characterization of N,N -t>is(3 pioolyl)-4-methoxy-isophthalamide (piootamide) as a dual thromboxane synthase inhibitor/thromboxane A2 receptor antagonist in human platelets. HircmibHaemost 1989 61 479-84... 

In a study ot the ettects ot aspirin 325 mg/day, both acute (4 hours atter the dose) and chronic (6 weeks), in 62 patients with mild to moderate heart tailure taking enala-pril (more than 10 mg/day tor at least 3 months), there were no significant changes in mean arterial pressure or in forearm blood flow and vascular resistance measured by venous plethysmography (112). In another arm ot the study the same results were observed with itetroban 250 mg/day, a thromboxane A2 receptor antagonist. 

Albuquerque, M.G., Hopfinger, A.J., Barreiro, E.J. and de Alencastro, R.B. (1998). Four-Dimensional Quantitative Structure-Activity Relationship Analysis of a Series of Interphenylene 7-Qxabicycloheptane Qxazole Thromboxane A2 Receptor Antagonists. J.Chem.InfComput.ScL, 38,925-938. 

In a series of benzimidazole-derived thromboxane A2 receptor antagonists described by Nicolai et the crucial element is the distance between the carboxylic group and the benzimidazole ring. A 200-fold increase in afhnity was observed when changing from propionic to a bntyric side-chain (Fignre 14.7). 

Nicolai, E., Goyard, J., Benchetrit, T., Teulon, J. M., Caussade, F., Virone, A., Delchambre, C., Cloarec, A. Synthesis and structure-activity relationships of novel benzimidazole and imidazo[4,5-h]pyridine acid derivatives as thromboxane A2 receptor antagonists. J. Med. Chem. 1992, 36, 1175-1187. 

Heinisch, G., Holzer, W., Kunz, F., Langer, T., Lukavsky, P, Pechlaner, C., Weissenberger, H. On the bioisosteric potential of diazines diazine analogues of the combined thromboxane A2 receptor antagonist and synthetase inhibitor ridogrel. 7. Med. Chem. 1996, 59(20), 4058-4064. 

Soyka, R., Heckel, A., Nickl, J., Eisert, W., Muller, T. H., Weisenberger, H. 6,6-Disubstituted hex-5-enoic add derivatives as combined thromboxane A2 receptor antagonists and synthetase inhibitors. J. Med. Chem. 1994, 37, 26-39. 

T.H. (1999) Guanidine derivatives as combined thromboxane A2 receptor antagonists and synthase inhibitors. J. Med. Chem. 42 1235-1249. 

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