Exploiting chemical diversity for drug discovery
Exploiting chemical diversity for drug discovery
复制标题
利用化学多样性进行药物发现
DOI：
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
M. Entzeroth
中科院分区：
文献类型：
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作者：
P. Bartlett;M. Entzeroth
第一部分：化学操作进展 第 1 章：利用聚合物辅助液相合成和自动化高通量制备生物活性化合物 1：简介 2：生物活性化合物的 PASP 合成方法 3：生物活性分子的 PASP 自动化合成 4：类药分子合成中的流程化学和自动化 5：结论 6： 参考文献 第 2 章：加速化学：微波、声化学和氟相技术 1：简介 2：微波增强化学 3：声化学作为加速合成的一种手段 4：氟相技术 5：结论 6：参考文献 第二部分：合成的概念进展 第 3 章：“非天然”天然产物的生物合成 1：简介 2：I 型聚酮化合物合成酶3：II型 聚酮化合物合成酶 4：III 型聚酮化合物合成酶 5：结论 6：致谢 7：参考文献 第 4 章：呕吐合成设计：新颖性与熟悉性的平衡 1：生物大分子 - 数量优势 2：低聚物合成 - 改进自然 3：随机、发现或探索图书馆 - 寻找通用支架 4：特权脚手架 - 看看哪里 光是最亮的 5：新型支架的装饰或合成 - 为弱势群体提供援助 6：目标类库 - 有目的的多样性 7：肽和核苷酸库 Redux 8：先导化合物发现或药物发现 - 尺寸很重要 9：用于组合化学的天然产物支架 - 为什么要重新发明轮子？ 10：从天然产物到类似天然产物的图书馆——傲慢还是进步？ 11：先导化合物发现和组合化学 - 我们学到了什么？ 12：参考文献 第 5 章：复合集合：获取、注释和访问 1：简介 2：商业产品 3：提供非专有、非并行综合库（共享池/“集合集合”）的公司 4：提供内部设计的并行综合库的公司 5：复合选择和数据库过滤 6：子结构相似性/相异性 7：药效团分析8： Lipinski 五法则 (LRoF) 9：拓扑极性表面积 (tPSA) 和血脑屏障渗透性 (LogBB) 10：溶解度 11：化学注释和基于药效基团的先导跳跃的使用示例 12：化合物采集 13：参考文献 第 6 章：化学多样性：定义和定量 1：简介 2：多样性指标 3：分子描述 4：降维 5： 子集选择和分类 6：结论 7：缩略语 8：参考文献 第三部分：挖掘：将热门图书馆转化为领先优势 第 7 章：重点图书馆：从大型多样性图书馆到重点图书馆方法的战略演变 1：引言 2：图书馆概念的协同、多学科方法 3：图书馆设计概念 4：重点图书馆 5：总结 6：参考文献 第 8 章：翻译将肽变成小分子 1: 肽作为药物：好的、坏的和丑陋的 2: 生物活性肽的起源 3: 将肽转化为小分子的一般策略 4: 定制肽序列以将其转化为小分子 5: 使用计算方法将肽配体转化为小分子 6: 参考文献 第四部分：筛选中的操作发展 第 9 章：高密度板、微阵列、 微流体 1：用于高通量测定的功能性高密度孔板 2：小体积样品的并行液体处理 3：芯片上的微阵列测定 4：多参数测定的前景 5：参考文献 第 10 章：用于化学库研究的荧光技术 1：简介 2：解离增强型稀土元素氟免疫测定 (DELFIA) 3：酶 片段互补 (EFC) 4: 荧光偏振 (FP) 5: 荧光相关光谱 (FCS) 6: 放大发光邻近均相测定 (Alphascreen) 7: 荧光共振能量转移 (FRET) 8: 生物发光共振能量转移 (BRET) 9: 均相时间分辨荧光 (HTRF) 10: 结论11： 参考文献 第 11 章：基于基因工程的细胞分析在体外药物发现中的应用 1：简介 2：基于细胞分析的基因工程 3：基于报告基因的分析 4：测量细胞内钙的分析 5：监测蛋白质-蛋白质相互作用的分析 6：结论和展望 7：参考文献 第 12 章：基于 NMR 的筛选，一种强大的工具基于片段的药物发现 1：简介 2：NMR 筛选：概述 方面 3：配体检测方法与目标检测方法 4：将 NMR 纳入药物发现过程 5：代表性案例研究 6：结论 7：参考文献 第 13 章：筛选化学微阵列：方法和应用 1：简介 2：化学微阵列的筛选 3：化学微阵列的应用 4：结论 5：参考文献 第五部分：先导化合物评估的概念进展 第 14 章：筛选/反筛选：早期评估 选择性的分析 1：简介 2：用于选择候选药物的方法 3：总结 4：参考文献 第 15 章：体外分析概念 - 药物活性、选择性和可靠性 1：简介 2：物理化学参数 3：渗透性 4：代谢 5：蛋白质结合 6：毒性 7：化合物选择性研究 8：结论与展望 9：参考文献 第 16 章：体内的硅替代物 特性：ADME 和毒理学行为分析 1：体内特性的计算机替代物 2：生物药物特性的估计 3：药代动力学特性的估计 4：毒理学特性的估计 5：替代数据和估计与生理模拟的整合 6：参考文献 第 17 章：在化学优化中使用高内涵筛选 1：简介 2：HCS 系统 3：示例展示的力量 HCS 4：总结
Part One: Operational Developments in Chemistry Chapter 1: The Use of Polymer-assisted Solution-phase Synthesis and Automation for the High-throughput Preparation of Biologically Active Compounds 1: Introduction 2: PASP Synthesis Approaches to Biologically Active Compounds 3: Automated PASP Synthesis of Biologically Active Molecules 4: Flow Chemistry and Automation in the Synthesis of Drug-Like Molecules 5: Conclusion 6: References Chapter 2: Accelerated Chemistry: Microwave, Sonochemical, and Fluorous Phase Techniques 1: Introduction 2: Microwave Enhanced Chemistry 3: Sonochemistry as a Means to Accelerate Synthesis 4: Fluorous Phase Techniques 5: Conclusion 6: References Part Two: Conceptual Advances in Synthesis Chapter 3: Biosynthesis of "Unnatural" Natural Products 1: Introduction 2: Type I Polyketide Synthases 3: Type II Polyketide Synthases 4: Type III Polyketide Synthase 5: Conclusions 6: Acknowledgements 7: References Chapter 4: Vombinatorial Synthetic Design: the Balance of Novelty and Familiarity 1: Biological Macromolecules - Strength in Numbers 2: Oligomer Synthesis - Improving on Mother Nature 3: Random, Discovery, or Prospecting Libraries - the Quest for the Universal Scaffold 4: Privileged Scaffolds - Look Where the Light is Brightest 5: The Decoration or Synthesis of Novel Scaffolds - Aid for the Underprivileged 6: Target Class Libraries - Diversity with a Purpose 7: Peptide and Nucleotide Libraries Redux 8: Lead Discovery or Drug Discovery - Size Does Matter 9: Natural Product Scaffolds for Combinatorial Chemistry - Why Re-invent the Wheel? 10: From Natural Products to Natural Product-like Libraries - Hubris or Progress? 11: Lead Discovery and Combinatorial Chemistry - What Have we Learned? 12: References Chapter 5: Compound Collections: Acquisition, Annotation, and Access 1: Introduction 2: Commercial Offerings 3: Companies Providing Non-proprietry, Non-parallel Synthesised Libraries (Shared-pool/"Collected Collections") 4: Companies Providing In-house Designed, Parallel Synthesised Libraries 5: Compound Selection and Database Filtering 6: Substructure Similarity/Dissimilarity 7: Pharmacophore Analysis 8: Lipinski Rule-of-Five (LRoF) 9: Topological Polar Surface Area (tPSA) and Blood-Brain-Barrier Permeability (LogBB) 10: Solubility 11: Examples of the Use of Chemical Annotation and Pharmacophore based lead-hopping 12: Compound Acquisition 13: References Chapter 6: Chemical Diversity: Definition and Quantification 1: Introduction 2: Diversity Metrics 3: Molecular Description 4: Dimensionality Reduction 5: Subset Selection and Classification 6: Conclusion 7: Abbreviations 8: References Part Three: Mining: Turning a Hit into a Lead Chapter 7: Focused Libraries: the Evolution in Strategy from Large Diversity Libraries to the Focused Library Approach 1: Introduction 2: A Synergistic, Multidisciplinary Approach to Library Conception 3: Library Design Concepts 4: Focused libraries 5: Summary 6: References Chapter 8: Translating Peptides into Small Molecules 1: Peptides as Drugs: The Good, the Bad and the Ugly 2: Origin of Biologically Active Peptides 3: General Strategy for Translating Peptides into Small Molecules 4: Tailoring Peptide Sequences for Their Translation into Small Molecules 5: Transformation of peptide Ligands into Small Molecules Using Computational Approaches 6: References Part Four: Operational Developments in Screening Chapter 9: High Density Plates, Microarrays, Microfluidics 1: Functional High-density Well Plates for High-throughput Assays 2: Parallel Liquid Handling of Low-volume Samples 3: Microarray Assays on Chips 4: Prospects for Multi-Parameter Assays 5: References Chapter 10: Fluorescence Technologies for the Investigation of Chemical Libraries 1: Introduction 2: Dissociation Enhanced Lanthanide Fluoroimmunoassay (DELFIA) 3: Enzyme Fragment Complementation (EFC) 4: Fluorescence Polarization (FP) 5: Fluorescence Correlation Spectroscopy (FCS) 6: Amplified Luminescent Proximity Homogeneous Assay (Alphascreen) 7: Fluorescence Resonance Energy Transfer (FRET) 8: Bioluminescence Resonance Energy Transfer (BRET) 9: Homogeneous Time Resolved Fluorescence (HTRF) 10: Conclusion 11: References Chapter 11: The Use of Genetically Engineered Cell-based Assays in in-vitro Drug Discovery 1: Introduction 2: Genetic Engineering for Cell-based Assays 3: Reporter-based Assays 4: Assays to Measure Intracellular Calcium 5: Assays to Monitor Protein-Protein Interactions 6: Conclusions and Outlook 7: References Chapter 12: NMR Based Screening, a Powerful Tool in Fragment-based Drug Discovery 1: Introduction 2: NMR Screening: General Aspects 3: Ligand- vs Traget-detected Methods 4: Incorporation of NMR into the Drug Discovery Process 5: Representative Case Studies 6: Conclusion 7: References Chapter 13: Screening Chemical Microarrays: Methods and Applications 1: Introduction 2: Screening of Chemical Microarrays 3: Applications of Chemical Microarrays 4: Conclusion 5: References Part Five: Conceptual Advances in Lead Evaluation Chapter 14: Screen/Counter-screen: Early Assessment of Selectivity 1: Introduction 2: Approaches Used for Selection of Drug Candidates 3: Summary 4: References Chapter 15: Concepts for in-vitro Profiling - Drug Activity, Selectivity and Liability 1: Introduction 2: Physico Chemical Parameters 3: Permeability 4: Metabolism 5: Protein Binding 6: Toxicity 7: Investigation of Compound Selectivity 8: Conclusion and Outlook 9: Reference Chapter 16: In silico Surrogates for in vivo Properties: Profiling for ADME and Toxicological Behavior 1: In silico Surrogates for in vivo Properties 2: Estimation of Biopharmaceutical Properties 3: Estimation of Pharmacokinetic Properties 4: Estimation of Toxicological Properties 5: Integration of Surrogate Data and Estimations with Physiological Simulation 6: References Chapter 17: Use of High Content Screening in Chemical Optimization 1: Introduction 2: HCS Systems 3: Examples Show the Power of HCS 4: Summary