Description |
1 online resource |
Series |
Methods and principles in medicinal chemistry ; v. 54 |
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Methods and principles in medicinal chemistry ; v. 54.
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Contents |
Front Matter -- Principles. Bioisosterism in Medicinal Chemistry / Nathan Brown -- Classical Bioisosteres / Caterina Barillari, Nathan Brown -- Consequences of Bioisosteric Replacement / Dennis A Smith, David S Millan -- Data. B: A Database of Bioisosteres and Bioanalogues / Istv̀n Ujv̀ry, Julian Hayward -- Mining the Cambridge Structural Database for Bioisosteres / Colin R Groom, Tjelvar S G Olsson, John W Liebeschuetz, David A Bardwell, Ian J Bruno, Frank H Allen -- Mining for Context-Sensitive Bioisosteric Replacements in Large Chemical Databases / George Papadatos, Michael J Bodkin, Valerie J Gillet, Peter Willett -- Methods. Physicochemical Properties / Peter Ertl -- Molecular Topology / Nathan Brown -- Molecular Shape / Pedro J Ballester, Nathan Brown -- Protein Structure / James E J Mills -- Applications. The Drug Guru Project / Kent D Stewart, Jason Shanley, Karam B Alsayyed Ahmed, J Phillip Bowen -- Bioisosteres of an NPY-Y5 Antagonist / Nicholas P Barton, Benjamin R Bellenie -- Perspectives from Medicinal Chemistry / Nicholas A Meanwell, Marcus Gastreich, Matthias Rarey, Mike Devereux, Paul L A Popelier, Gisbert Schneider, Peter Willett -- Index |
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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 |
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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 |
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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 |
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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 |
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6.4.3 Generation of Matched Molecular Pairs |
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 methodologi |
Bibliography |
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 |
Notes |
Print version record |
Subject |
Drugs -- Design.
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Pharmaceutical chemistry.
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Drug Design
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Chemistry, Pharmaceutical
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MEDICAL -- Drug Guides.
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MEDICAL -- Nursing -- Pharmacology.
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MEDICAL -- Pharmacology.
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MEDICAL -- Pharmacy.
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Drugs -- Design.
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Pharmaceutical chemistry.
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Form |
Electronic book
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Author |
Brown, Nathan (Medicinal chemist)
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Mannhold, Raimund, 1948-
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Kubinyi, Hugo.
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Folkers, Gerd.
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ISBN |
9783527654307 |
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3527654305 |
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9783527654338 |
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352765433X |
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