2,3-Benzodiazepine(2,3-BDZ) compounds represent a group of structurally diverse,smallmolecule antagonists of(R,S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid(AMPA)receptors.Antagonists of AMPA receptors ...2,3-Benzodiazepine(2,3-BDZ) compounds represent a group of structurally diverse,smallmolecule antagonists of(R,S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid(AMPA)receptors.Antagonists of AMPA receptors are drug candidates for potential treatment of a number of neurological disorders such as epilepsy,stroke and amyotrophic lateral sclerosis(ALS).How to make better inhibitors,such as 2,3-BDZs,has been an enduring quest in drug discovery.Among a few available tools to address this specific question for making better 2,3-BDZs,perhaps the best one is to use mechanistic clues from studies of the existing antagonists to design and discover more selective and more potent antagonists.Here I review recent work in this area,and propose some ideas in the continuing effort of developing newer 2,3-BDZs for tighter control of AMPA receptor activities in vivo.展开更多
o-Nitrophenylazide was reduced by SmI2 in anhydrous THF at room temperature to produce active intermediate 2 (samarium amide), "living" double-anion in situ which reacted smoothly with α，β-unsaturated ket...o-Nitrophenylazide was reduced by SmI2 in anhydrous THF at room temperature to produce active intermediate 2 (samarium amide), "living" double-anion in situ which reacted smoothly with α，β-unsaturated ketones to afford 2,3-dihydro-1H-1,5-benzodiazepines in good yields under mild and neutral conditions.展开更多
背景:3D打印技术可根据患者实际病情和治疗需求设计构建模型、手术导板和个性化植入体或固定物,在创伤性骨折修复中展示了巨大的应用前景。目的:综述3D打印技术在创伤性骨折中的应用。方法:检索Web of science、PubMed和中国知网数据库2...背景:3D打印技术可根据患者实际病情和治疗需求设计构建模型、手术导板和个性化植入体或固定物,在创伤性骨折修复中展示了巨大的应用前景。目的:综述3D打印技术在创伤性骨折中的应用。方法:检索Web of science、PubMed和中国知网数据库2020-2024年发表的创伤骨科领域3D打印技术应用的相关文献,英文检索词为“traumatic fracture,3D printing technology,digital model,surgical guide”,中文检索词为“创伤性骨折,3D打印技术,数字模型,手术导板”,经筛选和分析,最终纳入60篇文献进行分析。结果与结论:①创伤性骨折是各种致伤因素导致的骨骼连续性中断和完整性破坏的骨折现象,以可靠方案提高复位愈合效果,已成为骨外科相关研究领域亟需解决的热点问题;②3D打印技术是以数字模型数据为基础的,运用粉末状金属或聚合物等可黏合成型材料以立体光刻、沉积建模和光聚合物喷射等形式制造满足需求三维实体的技术,在数字骨科生物医学领域应用广泛;③3D打印技术在疾病诊断、术前规划、重建骨折三维模型、定制骨科植入体、定制固定支具及假肢、手术导板制作和骨缺损修复等方面发挥了显著的优势,可根据患者实际病情和治疗需求设计构建模型、手术导板和个性化植入体或固定物,为创伤性骨折的治疗提供了新的思路。展开更多
基金supported by NIH/NINDS Grant R01 NS060812a grant from Muscular Dystrophy Association(MDA)
文摘2,3-Benzodiazepine(2,3-BDZ) compounds represent a group of structurally diverse,smallmolecule antagonists of(R,S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid(AMPA)receptors.Antagonists of AMPA receptors are drug candidates for potential treatment of a number of neurological disorders such as epilepsy,stroke and amyotrophic lateral sclerosis(ALS).How to make better inhibitors,such as 2,3-BDZs,has been an enduring quest in drug discovery.Among a few available tools to address this specific question for making better 2,3-BDZs,perhaps the best one is to use mechanistic clues from studies of the existing antagonists to design and discover more selective and more potent antagonists.Here I review recent work in this area,and propose some ideas in the continuing effort of developing newer 2,3-BDZs for tighter control of AMPA receptor activities in vivo.
基金We thank the National Natural Science Foundation of China (Project No.29872010) NSF of Zhejiang province for financial support.
文摘o-Nitrophenylazide was reduced by SmI2 in anhydrous THF at room temperature to produce active intermediate 2 (samarium amide), "living" double-anion in situ which reacted smoothly with α，β-unsaturated ketones to afford 2,3-dihydro-1H-1,5-benzodiazepines in good yields under mild and neutral conditions.
