CGS 22652: A New Potent Thromboxane A₂ Receptor Antagonist with Selective Thromboxane A₂ Synthase Inhibitory Properties

Mechanisms of Hyperoxia-Induced Reductions in Retinal Blood Flow in Newborn Pig

“…Thromboxane and its analogs dosedependently constrict bovine retinal resistance vessels (Nielsen and Nyborg, 1990), and they are potent vasoconstrictors in the pig retinal circulation as well (Meyer, Flammer and Lu$ scher, 1993 ;Abran et al, 1994). Our finding that intravitreal delivery of the well-established thromboxane synthesis and receptor antagonist CGS 22652 (Cohen et al, 1992) attenuated the RBF response to hyperoxia by 46 % is indicative of an important role for this constrictor prostanoid in the retinal autoregulatory response to systemic hyperoxia. Because increases in thromboxane production in response to hyperoxia have been documented in nonretinal endothelial cells (Bjoro, Haugen and StrayPedersen, 1987), we would contend that retinal endothelium is one possible cell source of thromboxane.…”

“…Another group (Group 2, n l 5) was administered 20 µl BSS vehicle intravitreally 10 min prior to the second period of hyperoxia to test for the effect of vehicle pretreatment on the RBF response. These groups served as controls for the remaining five groups, which received a single intravitreal injection of drug 10 min prior to the second hyperoxic stimulus, as follows : Group 3 animals (n l 6) were given 2 nmol of CGS 22652, a thromboxane synthase inhibitor and a thromboxane receptor antagonist (Cohen et al, 1992). Group 4 animals (n l 6) were administered 12n5 nmol of dibromododecenyl methyl sulfonimide (DDMS), a competitive inhibitor of the P %&!…”

Synthesis and Biological Activity of Prostaglandin Analogs Containing Heteroatoms in the Cyclopentane Ring

“…8). The in vitro biological profile of compounds 101 to 106, as compared with two reference dual TxRA/TxSI compounds R68070 [71] and CGS 22652 [66,72] (Fig. 10) shown that all racemic isomeric compounds 101 to 104 were found to be potent inhibitors of the human platelet thromboxane synthase in isolated enzyme preparations.…”

“…In cynomolgous monkey a single 30 mg/kg oral dose of compound 105 resulted in total inhibition of U-46619 (Fig. 5) -induced ex vivo platelet aggregation for at least 8 h with a return to the predose values in 24 h. Likewise, thromboxane synthase inhibition was measured by the effect of compound 105 on serum thromboxane B 2 (TxB 2 , the principal metabolite of TxA 2 ) synthesis which was inhibited for 24 h with concomitant significant elevations of 6-keto-PGF 1α (the stable metabolite of PGI 2 ) and PGE 2 levels [66]. In resume, the (+)-enantiomer 105 exhibited a desirable biological profile for an orally active TxRA/TxSI agent.…”

“…8), a reference TxRA and CGS 22652, a dual TxRA/TxSI [66] have been assayed. It was observed that sulfides 82, 88 On the other hand, the TxRA activity was slightly reduced in all sulfoxides while it increased by a factor of two in the corresponding sulfones.…”