k-134-compound has been researched along with cilostamide* in 2 studies
2 other study(ies) available for k-134-compound and cilostamide
| Article | Year |
|---|---|
Potent effects of novel anti-platelet aggregatory cilostamide analogues on recombinant cyclic nucleotide phosphodiesterase isozyme activity.
The inhibitory potential of novel anti-platelet aggregatory cilostamide analogues on phosphodiesterase (PDE) isozyme activities was investigated with recombinant PDE isozymes expressed in a baculovirus/ Sf9 expression system. The recombinant enzymes (PDE1-PDE5 and PDE7) showed Km values and sensitivities to selective inhibitors similar to those reported previously for native enzymes purified from tissues. The cyclooctylurea derivative OPC-33540 (6-[3-[3-cyclooctyl-3-[(1R*,2R*)-2-hydroxycyclohexyl]ureido]-propoxy]-2(1H)-quinolinone) inhibited recombinant PDE3A (IC50 = 0.32 nM) more potently and selectively than the classical PDE3 inhibitors cilostamide, cilostazol, milrinone, and amrinone. The cyclopropylurea derivative OPC-33509 [(-)-6-[3-[3-cyclopropyl-3-[(1R,2R)-2-hydroxycyclohexyl]ureido]-propoxy]-2(1H)-quinolinone] was less potent (IC50 = 0.10 microM) than OPC-33540, demonstrating that the cyclooctyl moiety was important for a potent inhibitory effect. In platelets, OPC-33540 potentiated cyclic AMP accumulation concentration-dependently in both the absence and the presence of 3 nM prostaglandin E1 (PGE1) (doubling concentrations: 32.5 and 6.2 nM, respectively). OPC-33540 inhibited thrombin-induced platelet aggregation potently (Ic50 = 27.8 nM). The anti-platelet aggregation effect also was stimulated in the presence of 3 nM PGE1 (IC50 = 6.0 nM). There was a good correlation between the IC50 values of PDE3 inhibitors in this study for recombinant PDE3A activity and their IC50 values for thrombin-induced platelet aggregation (r = 0.998). These data demonstrated that OPC-33540 is a highly selective and potent PDE3 inhibitor and a useful probe for identification of the intracellular functions of PDE3. Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Blood Platelets; Cells, Cultured; Cyclic AMP; Cyclic Nucleotide Phosphodiesterases, Type 1; Cyclic Nucleotide Phosphodiesterases, Type 3; Humans; Isoenzymes; Platelet Aggregation; Platelet Aggregation Inhibitors; Quinolines; Quinolones; Recombinant Proteins; Semicarbazides; Urea | 2000 |
2(1H)-quinolinone derivatives as novel anti-arteriostenotic agents showing anti-thrombotic and anti-hyperplastic activities.
In order to search for anti-arteriostenotic agents, a series of 2(1H)-quinolinone derivatives was synthesized and evaluated for anti-thrombotic activity and for anti-hyperplastic activity. From this series, (-)-6-[3-[3-cyclopropyl-3-[(1R,2R)-2-hydroxycyclohexyl]ureido]propoxy]-2 (1H)-quinolinone (1p, OPC-33509) was selected as the best candidate by balancing the efficacy on anti-thrombosis and anti-hyperplasia. Topics: Animals; Arteriosclerosis; Cilostazol; Hyperplasia; Platelet Aggregation Inhibitors; Quinolines; Quinolones; Rabbits; Tetrazoles; Thrombosis; Urea | 1998 |