07431cam a2200769Ka 4500 ocn809920141 OCoLC 20171113140659.0 m o d cr cn||||||||| 120914s2012 nju ob 001 0 eng d 9783527654307 (electronic bk.) 3527654305 (electronic bk.) 9783527654338 (electronic bk.) 352765433X (electronic bk.) 9781280778537 (MyiLibrary) 1280778539 (MyiLibrary) AU@ 000050060930 DEBBG BV043395045 GBVCP 790038315 NZ1 14695005 NZ1 15290908 (OCoLC)809920141 (OCoLC)796383251 (OCoLC)796932644 (OCoLC)818880171 10.1002/9783527654307 Wiley InterScience http://www3.interscience.wiley.com DG1 eng pn DG1 OCLCO OCLCQ EBLCP N$T IDEBK CUS OCLCQ SFB OCLCQ YDXCP COO OHI OCLCF OCLCA OCLCQ DEBBG OCLCQ MAIN RS420 MED 023000 bisacsh MED 058170 bisacsh MED 071000 bisacsh MED 072000 bisacsh 615/.19 22 Bioisosteres in medicinal chemistry / [electronic resource] Hoboken : John Wiley & amp ; Sons, 2012. 1 online resource. text txt rdacontent computer c rdamedia online resource cr rdacarrier Methods and principles in medicinal chemistry ; v. 54 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. 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. 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. 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. 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. Print version record. Drugs Design. Pharmaceutical chemistry. MEDICAL Drug Guides. bisacsh MEDICAL Nursing Pharmacology. bisacsh MEDICAL Pharmacology. bisacsh MEDICAL Pharmacy. bisacsh Drugs Design. fast (OCoLC)fst00898790 Pharmaceutical chemistry. fast (OCoLC)fst01060115 Electronic books. Brown, Nathan (Medicinal chemist) Mannhold, Raimund, 1948- Kubinyi, Hugo. Folkers, Gerd. Wiley InterScience (Online service) Print version: Bioisosteres in medicinal chemistry. Hoboken : John Wiley & amp; Sons, 2012 9783527654338 (OCoLC)818880171 Methods and principles in medicinal chemistry ; v. 54. http://onlinelibrary.wiley.com/book/10.1002/9783527654307 Wiley Online Library ddc BK 206166 206166