Structure-Based Design of Tropane Derivatives as a Novel Series of CCR5 Antagonists with Broad-Spectrum Anti-HIV-1 Activities and Improved Oral Bioavailability

	Structure-Based Design of Tropane Derivatives as a Novel Series of CCR5 Antagonists with Broad-Spectrum Anti-HIV-1 Activities and Improved Oral Bioavailability
	Xie, X; Zheng, YG; Chen, H; Li, J; Luo, RH; Chen, L; Zheng, CB; Zhang, SR; Peng, PF; Ma, D; Yang, LM; Zheng, YT; Liu, H; Wang, J
	2022
发表期刊	JOURNAL OF MEDICINAL CHEMISTRY
ISSN	0022-2623
卷号	65 期号:24 页码:16526-16540
摘要	Blocking the entry of an HIV-1 targeting CCR5 coreceptor has emerged as an attractive strategy to develop HIV therapeutics. Maraviroc is the only CCR5 antagonist approved by 21 novel tropane derivatives (6-26) were designed and synthesized based on the CCR5-maraviroc complex structure. Among them, compounds 25 and 26 had comparable activity to maraviroc and presented more potent inhibitory activity against a series of HIV-1 strains. In addition, compound 26 exhibited synergistic or additive antiviral effects in combination with other antiretroviral agents. Compared to maraviroc, both 25 and 26 displayed higher C-max and AUC(0-infinity) and improved oral bioavailability in SD rats. In addition, compounds 25 and 26 showed no significant CYP450 inhibition and showed a novel binding mode with CCR5 different from that of maraviroc-CCR5. In summary, compounds 25 and 26 are promising drug candidates for the treatment of HIV-1 infection.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13840
专题	科研部门_分子免疫药理学（郑永唐）
推荐引用方式 GB/T 7714	Xie, X,Zheng, YG,Chen, H,et al. Structure-Based Design of Tropane Derivatives as a Novel Series of CCR5 Antagonists with Broad-Spectrum Anti-HIV-1 Activities and Improved Oral Bioavailability[J]. JOURNAL OF MEDICINAL CHEMISTRY,2022,65(24):16526-16540.
APA	Xie, X.,Zheng, YG.,Chen, H.,Li, J.,Luo, RH.,...&Wang, J.(2022).Structure-Based Design of Tropane Derivatives as a Novel Series of CCR5 Antagonists with Broad-Spectrum Anti-HIV-1 Activities and Improved Oral Bioavailability.JOURNAL OF MEDICINAL CHEMISTRY,65(24),16526-16540.
MLA	Xie, X,et al."Structure-Based Design of Tropane Derivatives as a Novel Series of CCR5 Antagonists with Broad-Spectrum Anti-HIV-1 Activities and Improved Oral Bioavailability".JOURNAL OF MEDICINAL CHEMISTRY 65.24(2022):16526-16540.

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
2023041157.pdf（4030KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文