High Throughput Analysis for Early Drug Discovery (eBook)

James Kyranos (Herausgeber)

eBook Download: PDF

2004 | 1. Auflage
204 Seiten
Elsevier Science (Verlag)
978-0-08-047292-8 (ISBN)

Infos

This book offers concise and unbiased presentations by synthetic and analytical chemists who have been involved in creating and moving the field of combinatorial chemistry into the academic and industrial mainstream. Since the synthetic method often dictates the appropriate types of analysis, each chapter or section begins with a description of the synthesis approach and its advantages. The description of various combinatorial and high-throughput parallel synthesis techniques provide a relevant point of entry for synthetic chemists who need to set up appropriate characterisation methods for his/her organisation. This is an invaluable resource for all organic and analytical chemists in the pharmaceutical, agrochemical, and biotechnology fields who are either involved in, or beginning to investigate combinatorial techniques to increase overall efficiency and productivity.

First reference to focus on the analytical side of synthesis

---

High Throughput Analysis for Early Drug Discovery offers concise and unbiased presentations by synthetic and analytical chemists who have been involved in creating and moving the field of combinatorial chemistry into the academic and industrial mainstream. Since the synthetic method often dictates the appropriate types of analysis, each chapter or section begins with a description of the synthesis approach and its advantages. The description of various combinatorial and high-throughput parallel synthesis techniques provide a relevant point of entry for synthetic chemists who need to set up appropriate characterisation methods for his/her organisation. This is an invaluable resource for all organic and analytical chemists in the pharmaceutical, agrochemical, and biotechnology fields who are either involved in, or beginning to investigate combinatorial techniques to increase overall efficiency and productivity. - First reference to focus on the analytical side of synthesis

Inhalt

Cover 1
Contents 5
Preface 9
List of Contributors 13
Acknowledgments 17
1 High Throughput Analysis of Combinatorial Libraries Encoded with Electrophoric Molecular Tags 18
1 Introduction 18
2 Tag Decode-Assisted Single Bead LC/MS Analysis(Library QA) 20
3 Statistical Considerations 21
4 Synthesis of the Encoded Statine Amide Library 22
5 Biological Screening 32
6 Corroborating Screening Structure Activity Relationship (SAR)Data with Library QA Analysis 38
7 New Developments 40
8 Conclusion 50
References 50
2 Analysis of a Combinatorial Library Synthesized Using a Split-and-Pool Irori MicroKan Method for Development and Production 54
1 Introduction 55
2 Instrumentation 56
3 Data Processing 58
4 Automated SPE System in 96-Well Plate Format 58
5 Results and Discussion 59
6 Library Development Stage 62
7 Library Production Stage 64
8 High Throughput Purification using SPE 65
9 100% QC by LC/UV/ELSD/MS and Analytical Reports 67
10 Future Trends 68
11 Conclusion 72
Acknowledgements 72
References 72
3 High Throughput Flow Injection Analysis–Mass Spectrometry 74
1 Introduction 74
2 Open-Access Mass Spectrometry 76
3 High-Speed Flow Injection Analysis–Mass Spectrometry 76
4 Other High Speed and High Throughput Instrumentationfor MW Measurement 84
5 Conclusion 87
Acknowledgements 87
References 87
4 High Throughput Flow Injection Analysis–Mass Spectrometry for Combinatorial Chemistry Using Electrospray Ionization 90
1 Introduction 91
2 High Throughput MUX Flow-Injection ESI and APCILow-Resolution Mass Spectral Analysis 91
3 High Throughput High-Resolution Exact-Mass FIA ESI-FTMS 101
4 Sample Preparation Methods for ESI-MS Analysis of DrugsBound to Resin Beads 105
5 Conclusions 108
Acknowledgements 109
References 109
5 Purity and Quantity Determination of Parallel Synthesis Compound Libraries 112
1 Introduction 113
2 Library Development and Production 113
3 Analytical Process 114
4 Purity Assessment 117
5 Quantity Determination 119
6 Fast Chromatography 120
7 High Throughput HPLC/Mass Spectrometry 122
8 Data Management 124
9 Experimental Methods 126
10 Conclusion 128
References 128
6 High Throughput Parallel LC/MS/ELSD of Combinatorial LibrariesUsing the Eight-Channel LCT System with MUX Technology 130
1 Introduction 130
2 Experimental 131
3 Results and Discussion 133
4 Future Trends 138
5 Conclusion 140
Acknowledgements 140
References 140
7 Purification and Analysis of Parallel Libraries 142
1 Introduction 143
2 Challenge 143
3 Discussion 145
4 Experimental Methods 160
5 Future Trends 162
6 Conclusion 163
Acknowledgements 163
References 163
8 Screening Single-Bead Combinatorial Libraries using Capillary HPLC and MALDI-TOF-MS 164
1 Introduction 164
2 Future Trends 174
3 Conclusion 177
References 177
9 The Role of NMR in the Analysis of Chemical Libraries 180
1 Introduction 180
2 Information Issues in SAR Generation 181
3 Combinatorial Chemistry and SAR Generation 183
4 The Value of Compound Analysis 185
5 High Throughput Analytical Characterization 186
6 NMR and CLND, How Accurate? 187
7 Case Study 1: Analysis of Meta-Substituted Anilinoamides 188
8 Case Study 2: Analysis of Hydrazone Library 189
9 NMR Automation Technology for Sample Handling 191
10 NMR Data Analysis 192
11 Case Study 3: Analysis of 96 Benzoylated Amines 193
12 Conclusion 197
Acknowledgements 198
References 198
Subject Index 200

Produkt-Details

• Erscheint lt. Verlag: 18.9.2004
• Sprache: englisch
• Themenwelt: Sachbuch/Ratgeber
• Themenwelt: Naturwissenschaften ► Biologie ► Biochemie
• Themenwelt: Naturwissenschaften ► Chemie ► Analytische Chemie
• Themenwelt: Naturwissenschaften ► Chemie ► Organische Chemie
• Themenwelt: Naturwissenschaften ► Physik / Astronomie ► Angewandte Physik
• Themenwelt: Technik ► Bauwesen
• ISBN-10: 0-08-047292-3 / 0080472923
• ISBN-13: 978-0-08-047292-8 / 9780080472928