179102-65-9
179102-65-9 性质
| 密度 | 1.383±0.06 g/cm3(Predicted) |
|---|---|
| 储存条件 | Store at -20°C |
| 溶解度 | 溶于二甲基亚砜 |
| 酸度系数(pKa) | 4.12±0.10(Predicted) |
179102-65-9 用途与合成方法
|
LTD 4 8.87 (pA2) |
TXA 2 Receptor 8.81 (pA2) |
YM158 antagonizes leukotriene (LT) D 4 and thromboxane (TX) A 2 receptors. Functional assays in vitro show that YM158 exhibits competitive dual antagonism of LTD 4 and TXA 2 receptor-mediated contraction of isolated guinea pig tracheae, with pA 2 values of about 8.87 and 8.81, respectively. Its antagonistic activity for the LTD 4 receptor is approximately 6.5 times less potent than that of Montelukast, and that for the TXA 2 receptor is 2.5 times more potent than that of Seratrodast. YM158 also inhibits PGD 2 - and PGF 2α -induced tracheal contractions. YM158 antagonizes the stable TXA 2 analog U46619-induced aggregation of both guinea pig and human platelets and inhibits the LTD 4 -induced contraction of guinea pig ileum. YM158 produces a concentration-dependent inhibition of guinea pig ileum contraction induced by 1 nM LTD 4 with an IC 50 value of 0.58 nM.
YM158, an orally active dual antagonist for LTD 4 and TXA 2 receptors, is expected to have a stronger antiasthmatic efficacy in a broader class of asthmatic patients than single antagonistic drugs.The effect of YM158 is examined on these asthmatic responses in mediator-controlled and passively sensitized guinea pigs. Because the inhibitory effects of YM158 on increase in the airway resistance induced by LTD 4 or U46619 are shown to be dose-dependent when p.o. administered 1 h before LTD 4 or U46619 injection, with ED 50 values of 8.6 and 14 mg/kg, respectively, the antagonistic activities of p.o. YM158 for LTD 4 and TXA 2 receptors are exhibited at the same dose range. Oral YM158 shows significant effects, approximately the same as the combination of Pranlukast and Daltroban on antigen-induced response under various conditions; namely, where LTD 4 is predominant, TXA 2 is predominant; or where both mediators participated equally. In groups not treated with Indomethacin, administration of Daltroban (10 mg/kg), a combination of Pranlukast (30 mg/kg) and Daltroban (10 mg/kg), or YM158 (30 mg/kg) significantly prolongs the onset time for asthmatic response and significantly suppresses symptoms.
