The Resource Bioisosteres in Medicinal Chemistry

Bioisosteres in Medicinal Chemistry

Label
Bioisosteres in Medicinal Chemistry
Title
Bioisosteres in Medicinal Chemistry
Creator
Contributor
Subject
Genre
Language
eng
Summary
Written with the practicing medicinal chemist in mind, this is the first modern handbook to systematically address the topic of bioisosterism. As such, it provides a ready reference on the principles and methods of bioisosteric replacement as a key tool in preclinical drug development. The first part provides an overview of bioisosterism, classical bioisosteres and typical molecular interactions that need to be considered, while the second part describes a number of molecular databases as sources of bioisosteric identification and rationalization. The third part covers the four key methodologies for bioisostere identification and replacement: physicochemical properties, topology, shape, and overlays of protein-ligand crystal structures. In the final part, several real-world examples of bioisosterism in drug discovery projects are discussed. With its detailed descriptions of databases, methods and real-life case studies, this is tailor-made for busy industrial researchers with little time for reading, while remaining easily accessible to novice drug developers due to its systematic structure and introductory section
Member of
Cataloging source
MiAaPQ
http://library.link/vocab/creatorName
Mannhold, Raimund
LC call number
RS403 -- .B76 2012eb
Literary form
non fiction
Nature of contents
dictionaries
http://library.link/vocab/relatedWorkOrContributorName
  • Kubinyi, Hugo
  • Brown, Nathan
  • ProQuest (Firm)
Series statement
Methods and Principles in Medicinal Chemistry Ser.
Series volume
v.54
http://library.link/vocab/subjectName
Pharmaceutical chemistry
Label
Bioisosteres in Medicinal Chemistry
Link
http://ebookcentral.proquest.com/lib/multco/detail.action?docID=945186
Instantiates
Publication
Copyright
Carrier category
online resource
Carrier category code
cr
Carrier MARC source
rdacarrier
Color
multicolored
Content category
text
Content type code
txt
Content type MARC source
rdacontent
Contents
  • Bioisosteres in Medicinal Chemistry -- Contents -- List of Contributors -- Preface -- A Personal Foreword -- Part One: Principles -- 1 Bioisosterism in Medicinal Chemistry -- 1.1 Introduction -- 1.2 Isosterism -- 1.3 Bioisosterism -- 1.4 Bioisosterism in Lead Optimization -- 1.4.1 Common Replacements in Medicinal Chemistry -- 1.4.2 Structure-Based Drug Design -- 1.4.3 Multiobjective Optimization -- 1.5 Conclusions -- References -- 2 Classical Bioisosteres -- 2.1 Introduction -- 2.2 Historical Background -- 2.3 Classical Bioisosteres -- 2.3.1 Monovalent Atoms and Groups -- 2.3.2 Bivalent Atoms and Groups -- 2.3.3 Trivalent Atoms and Groups -- 2.3.4 Tetravalent Atoms -- 2.3.5 Ring Equivalents -- 2.4 Nonclassical Bioisosteres -- 2.4.1 Carbonyl Group -- 2.4.2 Carboxylic Acid -- 2.4.3 Hydroxyl Group -- 2.4.4 Catechol -- 2.4.5 Halogens -- 2.4.6 Amide and Esters -- 2.4.7 Thiourea -- 2.4.8 Pyridine -- 2.4.9 Cyclic Versus Noncyclic Systems -- 2.5 Summary -- References -- 3 Consequences of Bioisosteric Replacement -- 3.1 Introduction -- 3.2 Bioisosteric Groupings to Improve Permeability -- 3.3 Bioisosteric Groupings to Lower Intrinsic Clearance -- 3.4 Bioisosteric Groupings to Improve Target Potency -- 3.5 Conclusions and Future Perspectives -- References -- Part Two: Data -- 4 BIOSTER: A Database of Bioisosteres and Bioanalogues -- 4.1 Introduction -- 4.2 Historical Overview and the Development of BIOSTER -- 4.2.1 Representation of Chemical Transformations for Reaction Databases -- 4.2.2 The Concept of ''Biosteric Transformation'' -- 4.2.3 Other Analogue and Bioisostere Databases -- 4.3 Description of BIOSTER Database -- 4.3.1 Coverage and Selection Criteria -- 4.3.2 Sources -- 4.3.3 Description of the Layout of Database Records -- 4.3.3.1 ID Code -- 4.3.3.2 Biosteric Transformation -- 4.3.3.3 Citation(s) -- 4.3.3.4 Activity -- 4.3.3.5 Fragments
  • 4.3.3.6 Component Molecules and Fragments -- 4.4 Examples -- 4.4.1 Benzodioxole Bioisosteres -- 4.4.2 Phenol Bioisosteres -- 4.4.3 Ketoamides -- 4.5 Applications -- 4.6 Summary -- 4.7 Appendix -- References -- 5 Mining the Cambridge Structural Database for Bioisosteres -- 5.1 Introduction -- 5.2 The Cambridge Structural Database -- 5.3 The Cambridge Structural Database System -- 5.3.1 ConQuest -- 5.3.2 Mercury -- 5.3.3 WebCSD -- 5.3.4 Knowledge-Based Libraries Derived from the CSD -- 5.4 The Relevance of the CSD to Drug Discovery -- 5.5 Assessing Bioisosteres: Conformational Aspects -- 5.6 Assessing Bioisosteres: Nonbonded Interactions -- 5.7 Finding Bioisosteres in the CSD: Scaffold Hopping and Fragment Linking -- 5.7.1 Scaffold Hopping -- 5.7.2 Fragment Linking -- 5.8 A Case Study: Bioisosterism of 1H-Tetrazole and Carboxylic Acid Groups -- 5.8.1 Conformational Mimicry -- 5.8.2 Intermolecular Interactions -- 5.9 Conclusions -- References -- 6 Mining for Context-Sensitive Bioisosteric Replacements in Large Chemical Databases -- 6.1 Introduction -- 6.2 Definitions -- 6.3 Background -- 6.4 Materials and Methods -- 6.4.1 Human Microsomal Metabolic Stability -- 6.4.2 Data Preprocessing -- 6.4.3 Generation of Matched Molecular Pairs -- 6.4.4 Context Descriptors -- 6.4.4.1 Whole Molecule Descriptors -- 6.4.4.2 Local Environment Descriptors -- 6.4.5 Binning of DP Values -- 6.4.6 Charts and Statistics -- 6.5 Results and Discussion -- 6.5.1 General Considerations -- 6.6 Conclusions -- References -- Part Three: Methods -- 7 Physicochemical Properties -- 7.1 Introduction -- 7.2 Methods to Identify Bioisosteric Analogues -- 7.3 Descriptors to Characterize Properties of Substituents and Spacers -- 7.4 Classical Methods for Navigation in the Substituent Space -- 7.5 Tools to Identify Bioisosteric Groups Based on Similarity in Their Properties -- 7.6 Conclusions
  • References -- 8 Molecular Topology -- 8.1 Introduction -- 8.2 Controlled Fuzziness -- 8.3 Graph Theory -- 8.4 Data Mining -- 8.4.1 Graph Matching -- 8.4.2 Fragmentation Methods -- 8.5 Topological Pharmacophores -- 8.6 Reduced Graphs -- 8.7 Summary -- References -- 9 Molecular Shape -- 9.1 Methods -- 9.1.1 Superposition-Based Shape Similarity Methods -- 9.1.2 Superposition-Free Shape Similarity Methods -- 9.1.3 Choosing a Shape Similarity Technique for a Particular Project -- 9.2 Applications -- 9.3 Future Prospects -- References -- 10 Protein Structure -- 10.1 Introduction -- 10.2 Database of Ligand-Protein Complexes -- 10.2.1 Extraction of Ligands -- 10.2.2 Assessment of Ligand and Protein Criteria -- 10.2.3 Cavity Generation -- 10.2.4 Generation and Validation of SMILES String -- 10.2.5 Generation of FASTA Sequence Files -- 10.2.6 Identification of Intermolecular Interactions -- 10.3 Generation of Ideas for Bioisosteres -- 10.3.1 Substructure Search -- 10.3.2 Sequence Search -- 10.3.3 Binding Pocket Superposition -- 10.3.4 Bioisostere Identification -- 10.4 Context-Specific Bioisostere Generation -- 10.5 Using Structure to Understand Common Bioisosteric Replacements -- 10.6 Conclusions -- References -- Part Four: Applications -- 11 The Drug Guru Project -- 11.1 Introduction -- 11.2 Implementation of Drug Guru -- 11.3 Bioisosteres -- 11.4 Application of Drug Guru -- 11.5 Quantitative Assessment of Drug Guru Transformations -- 11.6 Related Work -- 11.7 Summary: The Abbott Experience with the Drug Guru Project -- References -- 12 Bioisosteres of an NPY-Y5 Antagonist -- 12.1 Introduction -- 12.2 Background -- 12.3 Potential Bioisostere Approaches -- 12.4 Template Molecule Preparation -- 12.5 Database Molecule Preparation -- 12.6 Alignment and Scoring -- 12.7 Results and Monomer Selection -- 12.8 Synthesis and Screening -- 12.9 Discussion
  • 12.10 SAR and Developability Optimization -- 12.11 Summary and Conclusion -- References -- 13 Perspectives from Medicinal Chemistry -- 13.1 Introduction -- 13.2 Pragmatic Bioisostere Replacement in Medicinal Chemistry: A Software Maker.s Viewpoint -- 13.3 The Role of Quantum Chemistry in Bioisostere Prediction -- 13.4 Learn from ''Naturally Drug-Like'' Compounds -- 13.5 Bioisosterism at the University of Sheffield -- References -- Index
Control code
EBC945186
Dimensions
unknown
Edition
1st ed.
Extent
1 online resource (258 pages)
Form of item
online
Isbn
9783527654338
Media category
computer
Media MARC source
rdamedia
Media type code
c
Note
Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, 2017. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries.
Sound
unknown sound
Specific material designation
remote
System control number
  • (MiAaPQ)EBC945186
  • (Au-PeEL)EBL945186
  • (CaPaEBR)ebr10575526
  • (CaONFJC)MIL368892
  • (OCoLC)809920141
Label
Bioisosteres in Medicinal Chemistry
Link
http://ebookcentral.proquest.com/lib/multco/detail.action?docID=945186
Publication
Copyright
Carrier category
online resource
Carrier category code
cr
Carrier MARC source
rdacarrier
Color
multicolored
Content category
text
Content type code
txt
Content type MARC source
rdacontent
Contents
  • Bioisosteres in Medicinal Chemistry -- Contents -- List of Contributors -- Preface -- A Personal Foreword -- Part One: Principles -- 1 Bioisosterism in Medicinal Chemistry -- 1.1 Introduction -- 1.2 Isosterism -- 1.3 Bioisosterism -- 1.4 Bioisosterism in Lead Optimization -- 1.4.1 Common Replacements in Medicinal Chemistry -- 1.4.2 Structure-Based Drug Design -- 1.4.3 Multiobjective Optimization -- 1.5 Conclusions -- References -- 2 Classical Bioisosteres -- 2.1 Introduction -- 2.2 Historical Background -- 2.3 Classical Bioisosteres -- 2.3.1 Monovalent Atoms and Groups -- 2.3.2 Bivalent Atoms and Groups -- 2.3.3 Trivalent Atoms and Groups -- 2.3.4 Tetravalent Atoms -- 2.3.5 Ring Equivalents -- 2.4 Nonclassical Bioisosteres -- 2.4.1 Carbonyl Group -- 2.4.2 Carboxylic Acid -- 2.4.3 Hydroxyl Group -- 2.4.4 Catechol -- 2.4.5 Halogens -- 2.4.6 Amide and Esters -- 2.4.7 Thiourea -- 2.4.8 Pyridine -- 2.4.9 Cyclic Versus Noncyclic Systems -- 2.5 Summary -- References -- 3 Consequences of Bioisosteric Replacement -- 3.1 Introduction -- 3.2 Bioisosteric Groupings to Improve Permeability -- 3.3 Bioisosteric Groupings to Lower Intrinsic Clearance -- 3.4 Bioisosteric Groupings to Improve Target Potency -- 3.5 Conclusions and Future Perspectives -- References -- Part Two: Data -- 4 BIOSTER: A Database of Bioisosteres and Bioanalogues -- 4.1 Introduction -- 4.2 Historical Overview and the Development of BIOSTER -- 4.2.1 Representation of Chemical Transformations for Reaction Databases -- 4.2.2 The Concept of ''Biosteric Transformation'' -- 4.2.3 Other Analogue and Bioisostere Databases -- 4.3 Description of BIOSTER Database -- 4.3.1 Coverage and Selection Criteria -- 4.3.2 Sources -- 4.3.3 Description of the Layout of Database Records -- 4.3.3.1 ID Code -- 4.3.3.2 Biosteric Transformation -- 4.3.3.3 Citation(s) -- 4.3.3.4 Activity -- 4.3.3.5 Fragments
  • 4.3.3.6 Component Molecules and Fragments -- 4.4 Examples -- 4.4.1 Benzodioxole Bioisosteres -- 4.4.2 Phenol Bioisosteres -- 4.4.3 Ketoamides -- 4.5 Applications -- 4.6 Summary -- 4.7 Appendix -- References -- 5 Mining the Cambridge Structural Database for Bioisosteres -- 5.1 Introduction -- 5.2 The Cambridge Structural Database -- 5.3 The Cambridge Structural Database System -- 5.3.1 ConQuest -- 5.3.2 Mercury -- 5.3.3 WebCSD -- 5.3.4 Knowledge-Based Libraries Derived from the CSD -- 5.4 The Relevance of the CSD to Drug Discovery -- 5.5 Assessing Bioisosteres: Conformational Aspects -- 5.6 Assessing Bioisosteres: Nonbonded Interactions -- 5.7 Finding Bioisosteres in the CSD: Scaffold Hopping and Fragment Linking -- 5.7.1 Scaffold Hopping -- 5.7.2 Fragment Linking -- 5.8 A Case Study: Bioisosterism of 1H-Tetrazole and Carboxylic Acid Groups -- 5.8.1 Conformational Mimicry -- 5.8.2 Intermolecular Interactions -- 5.9 Conclusions -- References -- 6 Mining for Context-Sensitive Bioisosteric Replacements in Large Chemical Databases -- 6.1 Introduction -- 6.2 Definitions -- 6.3 Background -- 6.4 Materials and Methods -- 6.4.1 Human Microsomal Metabolic Stability -- 6.4.2 Data Preprocessing -- 6.4.3 Generation of Matched Molecular Pairs -- 6.4.4 Context Descriptors -- 6.4.4.1 Whole Molecule Descriptors -- 6.4.4.2 Local Environment Descriptors -- 6.4.5 Binning of DP Values -- 6.4.6 Charts and Statistics -- 6.5 Results and Discussion -- 6.5.1 General Considerations -- 6.6 Conclusions -- References -- Part Three: Methods -- 7 Physicochemical Properties -- 7.1 Introduction -- 7.2 Methods to Identify Bioisosteric Analogues -- 7.3 Descriptors to Characterize Properties of Substituents and Spacers -- 7.4 Classical Methods for Navigation in the Substituent Space -- 7.5 Tools to Identify Bioisosteric Groups Based on Similarity in Their Properties -- 7.6 Conclusions
  • References -- 8 Molecular Topology -- 8.1 Introduction -- 8.2 Controlled Fuzziness -- 8.3 Graph Theory -- 8.4 Data Mining -- 8.4.1 Graph Matching -- 8.4.2 Fragmentation Methods -- 8.5 Topological Pharmacophores -- 8.6 Reduced Graphs -- 8.7 Summary -- References -- 9 Molecular Shape -- 9.1 Methods -- 9.1.1 Superposition-Based Shape Similarity Methods -- 9.1.2 Superposition-Free Shape Similarity Methods -- 9.1.3 Choosing a Shape Similarity Technique for a Particular Project -- 9.2 Applications -- 9.3 Future Prospects -- References -- 10 Protein Structure -- 10.1 Introduction -- 10.2 Database of Ligand-Protein Complexes -- 10.2.1 Extraction of Ligands -- 10.2.2 Assessment of Ligand and Protein Criteria -- 10.2.3 Cavity Generation -- 10.2.4 Generation and Validation of SMILES String -- 10.2.5 Generation of FASTA Sequence Files -- 10.2.6 Identification of Intermolecular Interactions -- 10.3 Generation of Ideas for Bioisosteres -- 10.3.1 Substructure Search -- 10.3.2 Sequence Search -- 10.3.3 Binding Pocket Superposition -- 10.3.4 Bioisostere Identification -- 10.4 Context-Specific Bioisostere Generation -- 10.5 Using Structure to Understand Common Bioisosteric Replacements -- 10.6 Conclusions -- References -- Part Four: Applications -- 11 The Drug Guru Project -- 11.1 Introduction -- 11.2 Implementation of Drug Guru -- 11.3 Bioisosteres -- 11.4 Application of Drug Guru -- 11.5 Quantitative Assessment of Drug Guru Transformations -- 11.6 Related Work -- 11.7 Summary: The Abbott Experience with the Drug Guru Project -- References -- 12 Bioisosteres of an NPY-Y5 Antagonist -- 12.1 Introduction -- 12.2 Background -- 12.3 Potential Bioisostere Approaches -- 12.4 Template Molecule Preparation -- 12.5 Database Molecule Preparation -- 12.6 Alignment and Scoring -- 12.7 Results and Monomer Selection -- 12.8 Synthesis and Screening -- 12.9 Discussion
  • 12.10 SAR and Developability Optimization -- 12.11 Summary and Conclusion -- References -- 13 Perspectives from Medicinal Chemistry -- 13.1 Introduction -- 13.2 Pragmatic Bioisostere Replacement in Medicinal Chemistry: A Software Maker.s Viewpoint -- 13.3 The Role of Quantum Chemistry in Bioisostere Prediction -- 13.4 Learn from ''Naturally Drug-Like'' Compounds -- 13.5 Bioisosterism at the University of Sheffield -- References -- Index
Control code
EBC945186
Dimensions
unknown
Edition
1st ed.
Extent
1 online resource (258 pages)
Form of item
online
Isbn
9783527654338
Media category
computer
Media MARC source
rdamedia
Media type code
c
Note
Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, 2017. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries.
Sound
unknown sound
Specific material designation
remote
System control number
  • (MiAaPQ)EBC945186
  • (Au-PeEL)EBL945186
  • (CaPaEBR)ebr10575526
  • (CaONFJC)MIL368892
  • (OCoLC)809920141

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