7-Amino-3-phenyl-2-methyl-pyrazolopyrimidine衍生物抑制了人类犀牛病毒的复制
Prashant Chakrasali1, Dasom Hwang2, Joo-Youn Lee2
1Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea; Department of Medicinal and Pharmaceutical Chemistry, University of Science and Technology, Daejeon, 34113, Republic of Korea.
European journal of medicinal chemistry
|July 20, 2024
概括
研究人员发现了一种新的pyrazolo-pyrimidine衍生物6f,它显示出广泛的肠道病毒抑制活性. 这种化合物向PI4KIIIβ,并显示出有前途的潜力,作为开发针对各种肠道病毒的新型抗病毒药物的头.
科学领域:
- 药用化学 医学化学
- 病毒学 病毒学
- 药物发现 药物发现 药物发现
背景情况:
- 针对病毒复制蛋白的小分子对于抗病毒药物发现至关重要.
- 肠道病毒感染是一个重大的公共卫生挑战,需要新的治疗策略.
- 人类犀利病毒 (hRV) 和其他肠道病毒是重要的病原体.
研究的目的:
- 为了确定人类犀利病毒 (hRV) 复制的新型抑制剂.
- 发现具有广谱肠道病毒抑制活性的小分子.
- 优化化合物以提高抗病毒功效和有利的药理动力学特性.
主要方法:
- 来自韩国化学银行图书馆的10万种化合物的高通量选.
- 识别和表征的酸-4-酶IIIβ (PI4KIIIβ) 抑制剂.
- 在体外抗病毒活性试验 (EC50),细胞毒性试验 (CC50),激酶抑制试验 (IC50),肝脏微粒稳定性试验以及体内药理学研究.
主要成果:
- 两种pyrazolo-pyrimidine衍生物被确定为PI4KIIIβ抑制剂,具有中度的抗鼻病毒活性.
- 衍生品6f对hRV-B14,hRV-A16和hRV-A21表现出强烈的活性 (EC50=0.0440.083μM),具有中等毒性 (CC50=31.38μM).
- 化合物6f对包括EV-A71和EV-D68在内的各种肠道病毒表现出广泛的活性,具有选择性的PI4KIIIβ抑制和良好的体内药理动力学.
结论:
- 这种pyrazolo-pyrimidine衍生物6f是一种强效和选择性的PI4KIIIβ抑制剂,具有广谱肠道病毒活性.
- 化合物6f表现出有希望的抗病毒疗效,中度毒性和可取的药用动力学特征.
- 6f (KR-26549) 是一种理想的化合物,可以用于开发新的抗病毒疗法来治疗肠道病毒感染.
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