Bioisosteres in medicinal chemistry.

• Συγγραφή απο Οργανισμό/Αρχή: Wiley InterScience (Online service)
• Άλλοι συγγραφείς: Brown, Nathan (Medicinal chemist), Mannhold, Raimund, 1948-, Kubinyi, Hugo, Folkers, Gerd
• Μορφή: Ηλ. βιβλίο
• Γλώσσα: English
• Έκδοση: Hoboken : Sons, John Wiley & amp ; 2012.
• Σειρά: Methods and principles in medicinal chemistry ; v. 54.
• Θέματα: Drugs > Design.; Pharmaceutical chemistry.; MEDICAL > Drug Guides.; MEDICAL > Nursing > Pharmacology.; MEDICAL > Pharmacology.; MEDICAL > Pharmacy.; Electronic books.

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 par...

Πίνακας περιεχομένων:

• 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.