高级检索
当前位置: 首页 > 详情页

Design, synthesis, and biological evaluation of deuterated apalutamide with improved pharmacokinetic profiles.

文献详情

资源类型:
机构: [a]Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan 610041, China [b]University of Chinese Academy of Sciences, Beijing 100049, China [c]Hinova Pharmaceuticals Inc., Suite 301, Rongyao Building B, #5 South KeYuan Road, Chengdu, Sichuan 610041, China [d]Lab of YWChen, Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China
出处:
ISSN:

关键词: Apalutamide Castration-resistant prostate cancer AR antagonist Deuterium kinetic isotope effect Pharmacokinetic

摘要:
A series of deuterated apalutamide were designed and prepared. Compared to its prototype compound 18, deuterated analogues 19 and 21 showed obviously higher plasma concentrations and better PK parameters after oral administration in mice. In rats, N-trideuteromethyl compound 19 displayed 1.8-fold peak concentration (Cmax), and nearly doubled its drug exposure in plasma (AUC0-∞) compared to compound 18. Unsurprisingly, compounds 18 and 19 had similar affinity for AR in vitro. In summary, the deuteration strategy could obviously improve PK parameters of apalutamide. Copyright © 2017 Elsevier Ltd. All rights reserved.

基金:
语种:
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2017]版:
大类 | 3 区 医学
小类 | 3 区 有机化学 4 区 药物化学
最新[2023]版:
大类 | 4 区 医学
小类 | 2 区 有机化学 4 区 药物化学
第一作者:
第一作者机构: [a]Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan 610041, China [b]University of Chinese Academy of Sciences, Beijing 100049, China
通讯作者:
通讯机构: [a]Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan 610041, China [b]University of Chinese Academy of Sciences, Beijing 100049, China [c]Hinova Pharmaceuticals Inc., Suite 301, Rongyao Building B, #5 South KeYuan Road, Chengdu, Sichuan 610041, China [d]Lab of YWChen, Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China [*1]Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan 610041, China.
推荐引用方式(GB/T 7714):
APA:
MLA:

资源点击量:43389 今日访问量:0 总访问量:3120 更新日期:2024-09-01 建议使用谷歌、火狐浏览器 常见问题

版权所有©2020 四川省肿瘤医院 技术支持:重庆聚合科技有限公司 地址:成都市人民南路四段55号