基于C,C'-diphenyl-m-carborane支架的非二类VDR配体的设计,合成和结构开发
Hansaka Nirupama Thilakarathne Narasinghe Mudiyanselage1, Takashi Misawa2, Kotaro Ochiai3
1Laboratory for Biomaterials and Bioengineering, Institute of Integrated Research, Institute of Science Tokyo, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan; Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
基于二-m-碳基框架的新型非二类维生素D受体 (VDR) 配体显示出治疗骨质疏松症和癌症等疾病的强大活性. 它们的多样化的绑定模式突出显示了VDR.
科学领域:
- 药用化学 医学化学
- 结构生物学 结构生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 非类固醇维生素D受体 (VDR) 配体对于治疗骨质疏松症,牛皮和癌症至关重要.
- 开发具有独特结构的新型VDR配体对于治疗进步至关重要.
研究的目的:
- 设计,合成和评估新型的1,7-二-m-碳衍生物作为非二类VDR配体.
- 研究这些新型化合物的结构-活性关系和结合方式.
主要方法:
- 1,7-二-m-碳衍生物的化学合成.
- 生物评估VDR连接剂功效的生物评估.
- 用于共同晶体结构分析的X射线晶体学.
主要成果:
- 鉴定出强大的VDR配体,包括化合物12b和13a,基于二-m-碳基框架.
- 在具有不同链长度的化合物中观察到类似的强度.
- 通过X射线结晶学揭示了多种联体-VDR相互作用模式,证明了VDR的结合口袋可塑性.
结论:
- 1,7-二-m-碳基基架是开发强大的非二类VDR配体的可行核心.
- VDR联体结合口袋的形状灵活性允许各种结合模式,而不会影响活动.
- 这些carborane衍生物代表了未来在VDR相关疾病中药物开发的有希望的线索.
更多相关视频
04:51Author Spotlight: Functionalizing Metal-Organic Frameworks: Advancements, Challenges, and the Power of Post-Synthetic Ligand Exchange
Published on: June 23, 2023
10:33Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
Published on: October 26, 2015
相关概念视频
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
Structure of Conjugated Dienes
Conjugated dienes are compounds characterized by the presence of alternating double and single bonds. In a conjugated system like 1,3-butadiene, the unhybridized 2p orbital on each carbon overlaps continuously, allowing the π electrons to be delocalized across the entire molecule. In contrast, this type of overlap does not occur in cumulated and isolated dienes, such as 2,3-pentadiene and 1,4-pentadiene, respectively. Instead, the π electrons remain localized between the double...
Cycloaddition Reactions: Overview
