4-[4-[[(3R)-1-丁基-3-[(R)-环己基羟基甲基]-2,5-二氧代-1,4,9-三氮杂螺[5.5]十一烷-9-基]甲基]苯氧基]苯甲酸
4-[4-[[(3R)-1-丁基-3-[(R)-环己基羟基甲基]-2,5-二氧代-1,4,9-三氮杂螺[5.5]十一烷-9-基]甲基]苯氧基]苯甲酸
![4-[4-[[(3R)-1-丁基-3-[(R)-环己基羟基甲基]-2,5-二氧代-1,4,9-三氮杂螺[5.5]十一烷-9-基]甲基]苯氧基]苯甲酸 结构式](https://img.chemicalbook.com/CAS/20150408/GIF/461443-59-4.gif)
4-[4-[[(3R)-1-丁基-3-[(R)-环己基羟基甲基]-2,5-二氧代-1,4,9-三氮杂螺[5.5]十一烷-9-基]甲基]苯氧基]苯甲酸 性质
| 沸点 | 800.6±65.0 °C(Predicted) |
|---|---|
| 密度 | 1.29 |
| 储存条件 | Store at -20°C |
| 溶解度 | 溶于二甲基亚砜 |
| 酸度系数(pKa) | 4.29±0.10(Predicted) |
4-[4-[[(3R)-1-丁基-3-[(R)-环己基羟基甲基]-2,5-二氧代-1,4,9-三氮杂螺[5.5]十一烷-9-基]甲基]苯氧基]苯甲酸 用途与合成方法
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HIV-1 Ba-L 0.4 nM (IC 50 ) |
HIV-1 JRFL 0.1 nM (IC 50 ) |
HIV-1 MOKW 0.2 nM (IC 50 ) |
CCR5
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Aplaviroc (AK602) is identified as the most potent agent among newly designed and synthesized SDP derivatives. Aplaviroc exerts potent activity against three wild-type R5 HIV-1 strains (HIV-1 Ba-L , HIV-1 JRFL and HIV-1 MOKW ) with IC 50 values of 0.1 to 0.4 nM. It is of note that Aplaviroc is substantially more potent than two previously published CCR5 inhibitors, E921/TAK-779 and AK671/SCH-C. The activity of Aplaviroc’s anti-HIV-1 is limited and similar to that seen for zidovudine. Moreover, Aplaviroc suppresses the infectivity and replication of two HIV-1 MDR variants, HIV-1 MM and HIV-1 JSL , at extremely low concentrations (IC 50 values of 0.4 to 0.6 nM), while these two R5 HIV-1 variants are less susceptible to zidovudine, nelfinavir, and saquinavir. Aplaviroc binds to CCR5 with high affinity. The K d values thus determined for Aplaviroc, E913, E921/TAK-779, and AK671/SCH-C are 2.9±1.0, 111.7±3.5, 32.2±9.6, and 16.0±1.5 nM, respectively. Aplaviroc potently blocks rgp120/sCD4 binding to CCR5 with an IC 50 value of 2.7 nM. These results suggest that the potent activity of Aplaviroc against R5 HIV-1 stems from its binding to ECL2B and/or its vicinity with high affinity, resulting in inhibition of gp120/CD4 binding to CCR5.
