{"product_id":"practical-medicinal-chemistry-with-macrocycles-9781119092568","title":"Practical Medicinal Chemistry with Macrocycles","description":"\u003cb\u003eBook Synopsis\u003c\/b\u003e\u003cbr\u003e\u003cp\u003eIncluding case studies of macrocyclic marketed drugs and macrocycles in drug development, this book helps medicinal chemists deal with the synthetic and conceptual challenges of macrocycles in drug discovery efforts.\u003c\/p\u003e \u003cul\u003e \u003cli\u003eProvides needed background to build a program in macrocycle drug discovery design criteria, macrocycle profiles, applications, and limitations\u003c\/li\u003e \u003cli\u003eFeatures chapters contributed from leading international figures involved in macrocyclic drug discovery efforts\u003c\/li\u003e \u003cli\u003eCovers design criteria, typical profile of current macrocycles, applications, and limitations\u003c\/li\u003e \u003c\/ul\u003e\u003cbr\u003e\u003cbr\u003e\u003cb\u003eTable of Contents\u003c\/b\u003e\u003cbr\u003e\u003cp\u003eForeword xiii\u003c\/p\u003e \u003cp\u003eIntroduction xv\u003c\/p\u003e \u003cp\u003eAbout the Contributors xix\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart I Challenges Specific to Macrocycles 1\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1 Contemporary Macrocyclization Technologies 3\u003cbr\u003e\u003ci\u003eSerge Zaretsky and Andrei K. Yudin\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e1.1 Introduction 3\u003c\/p\u003e \u003cp\u003e1.2 Challenges Inherent to the Synthesis of Macrocycles 3\u003c\/p\u003e \u003cp\u003e1.3 Challenges in Macrocycle Characterization 6\u003c\/p\u003e \u003cp\u003e1.4 Macrocyclization Methods 8\u003c\/p\u003e \u003cp\u003e1.5 Cyclization on the Solid Phase 14\u003c\/p\u003e \u003cp\u003e1.6 Summary 17\u003c\/p\u003e \u003cp\u003eReferences 18\u003c\/p\u003e \u003cp\u003e2 A Practical Guide to Structural Aspects of Macrocycles (NMR, X]Ray, and Modeling) 25\u003cbr\u003e\u003ci\u003eDavid J. Craik, Quentin Kaas and Conan K. Wang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e2.1 Background 25\u003c\/p\u003e \u003cp\u003e2.2 Experimental Studies of Macrocycles 31\u003c\/p\u003e \u003cp\u003e2.3 Molecular Modeling of Macrocyclic Peptides 38\u003c\/p\u003e \u003cp\u003e2.4 Summary 46\u003c\/p\u003e \u003cp\u003eAcknowledgments 47\u003c\/p\u003e \u003cp\u003eReferences 47\u003c\/p\u003e \u003cp\u003e3 Designing Orally Bioavailable Peptide and Peptoid Macrocycles 59\u003cbr\u003e\u003ci\u003eDavid A. Price, Alan M. Mathiowetz and Spiros Liras\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e3.1 Introduction 59\u003c\/p\u003e \u003cp\u003e3.2 Improving Peptide Plasma Half]Life 60\u003c\/p\u003e \u003cp\u003e3.3 Absorption, Bioavailability, and Methods for Predicting Absorption 61\u003c\/p\u003e \u003cp\u003e3.4 In Silico Modeling 70\u003c\/p\u003e \u003cp\u003e3.5 Future Directions 71\u003c\/p\u003e \u003cp\u003eReferences 72\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart II Classes of Macrocycles and Their Potential for Drug Discovery 77\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e4 Natural and Nature]Inspired Macrocycles: A Chemoinformatic Overview and Relevant Examples 79\u003cbr\u003e\u003ci\u003eLudger A. Wessjohann, Richard Bartelt and Wolfgang Brandt\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e4.1 Introduction to Natural Macrocycles as Drugs and Drug Leads 79\u003c\/p\u003e \u003cp\u003e4.2 Biosynthetic  Pathways, Natural Role, and Biotechnological Access 79\u003c\/p\u003e \u003cp\u003e4.3 QSAR and Chemoinformatic Analyses of Common Features 84\u003c\/p\u003e \u003cp\u003e4.4 Case Studies: Selected Natural Macrocycles of Special Relevance in Medicinal Chemistry 88\u003c\/p\u003e \u003cp\u003eReferences 91\u003c\/p\u003e \u003cp\u003e5 Bioactive and Membrane]Permeable Cyclic Peptide Natural Products 101\u003cbr\u003e\u003ci\u003eAndrew T. Bockus and R. Scott Lokey\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e5.1 Introduction 101\u003c\/p\u003e \u003cp\u003e5.2 Structural Motifs and Permeability of Cyclic Peptide Natural Products 101\u003c\/p\u003e \u003cp\u003e5.3 Conformations of Passively Permeable Bioactive Cyclic Peptide Natural Products 103\u003c\/p\u003e \u003cp\u003e5.4 Recently Discovered Bioactive Cyclic Peptide Natural Products 108\u003c\/p\u003e \u003cp\u003e5.5 Conclusions 125\u003c\/p\u003e \u003cp\u003eReferences 125\u003c\/p\u003e \u003cp\u003e6 Chemical Approaches to Macrocycle Libraries 133\u003cbr\u003e\u003ci\u003eZiqing Qian, Patrick G. Dougherty and Dehua Pei\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e6.1 Introduction 133\u003c\/p\u003e \u003cp\u003e6.2 Challenges Associated with Macrocyclic One]Bead]One-Compound Libraries 134\u003c\/p\u003e \u003cp\u003e6.3 Deconvolution of Macrocyclic Libraries 134\u003c\/p\u003e \u003cp\u003e6.4 Peptide]Encoded Macrocyclic Libraries 136\u003c\/p\u003e \u003cp\u003e6.5 DNA] Encoded Macrocyclic Libraries 142\u003c\/p\u003e \u003cp\u003e6.6 Parallel Synthesis of Macrocyclic Libraries 142\u003c\/p\u003e \u003cp\u003e6.7 Diversity] Oriented Synthesis 145\u003c\/p\u003e \u003cp\u003e6.8 Perspective 147\u003c\/p\u003e \u003cp\u003e6.9 Conclusion 149\u003c\/p\u003e \u003cp\u003eReferences 150\u003c\/p\u003e \u003cp\u003e7 Biological and Hybrid Biological\/Chemical Strategies in Diversity Generation of Peptidic Macrocycles 155\u003cbr\u003e\u003ci\u003eFrancesca Vitali and Rudi Fasan\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e7.1 Introduction 155\u003c\/p\u003e \u003cp\u003e7.2 Cyclic Peptide Libraries on Phage Particles 155\u003c\/p\u003e \u003cp\u003e7.3 Macrocyclic Peptide Libraries via In Vitro Translation 166\u003c\/p\u003e \u003cp\u003e7.4 Emerging Strategies for the Combinatorial Synthesis of Hybrid Macrocycles In Vitro and in Cells 171\u003c\/p\u003e \u003cp\u003e7.5 Comparative Analysis of Technologies 175\u003c\/p\u003e \u003cp\u003e7.6 Conclusions 178\u003c\/p\u003e \u003cp\u003eReferences 178\u003c\/p\u003e \u003cp\u003e8 Macrocycles for Protein–Protein Interactions 185\u003cbr\u003e\u003ci\u003eEilidh Leitch and Ali Tavassoli\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e8.1 Introduction 185\u003c\/p\u003e \u003cp\u003e8.2 Library Approaches to Macrocyclic PPI Inhibitors 186\u003c\/p\u003e \u003cp\u003e8.3 Structural Mimicry 192\u003c\/p\u003e \u003cp\u003e8.4 Multi] Cycles for PPIs 197\u003c\/p\u003e \u003cp\u003e8.5 The Future for Targeting PPIs with Macrocycles 197\u003c\/p\u003e \u003cp\u003eReferences 200\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart III The Synthetic Toolbox for Macrocycles 205\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e9 Synthetic Strategies for Macrocyclic Peptides 207\u003cbr\u003e\u003ci\u003eÉ\u003c\/i\u003e\u003ci\u003eric Biron, Simon Vezina\u003c\/i\u003e\u003ci\u003e]\u003c\/i\u003e\u003ci\u003eDawod and Fran\u003c\/i\u003e\u003ci\u003eç\u003c\/i\u003e\u003ci\u003eois B\u003c\/i\u003e\u003ci\u003eé\u003c\/i\u003e\u003ci\u003edard\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e9.1 Introduction to Peptide Macrocyclization 207\u003c\/p\u003e \u003cp\u003e9.2 One Size Does Not Fit All: Factors to Consider During Synthesis Design 209\u003c\/p\u003e \u003cp\u003e9.3 Peptide Macrocyclization in Solution 213\u003c\/p\u003e \u003cp\u003e9.4 Peptide Macrocyclization on Solid Support 220\u003c\/p\u003e \u003cp\u003e9.5 Peptide Macrocyclization by Disulfide Bond Formation 226\u003c\/p\u003e \u003cp\u003e9.6 Conclusion 229\u003c\/p\u003e \u003cp\u003eReferences 230\u003c\/p\u003e \u003cp\u003e10 Ring]Closing Metathesis]Based Methods in Chemical Biology: Building a Natural Product Inspired Macrocyclic Toolbox to Tackle Protein–Protein Interactions 243\u003cbr\u003e\u003ci\u003eJagan Gaddam, Naveen Kumar Mallurwar, Saidulu Konda, Mahender Khatravath, Madhu Aeluri, Prasenjit Mitra and Prabhat Arya\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e10.1 Introduction 243\u003c\/p\u003e \u003cp\u003e10.2 Protein– Protein Interactions: Challenges and Opportunities 243\u003c\/p\u003e \u003cp\u003e10.3 Natural Products as Modulators of Protein–Protein Interactions 243\u003c\/p\u003e \u003cp\u003e10.4 Introduction to Ring]Closing Metathesis 244\u003c\/p\u003e \u003cp\u003e10.5 Selected Examples of Synthetic Macrocyclic Probes Using RCM]Based Approaches 246\u003c\/p\u003e \u003cp\u003e10.6 Summary 259\u003c\/p\u003e \u003cp\u003eReferences 259\u003c\/p\u003e \u003cp\u003e11 The Synthesis of Peptide-Based Macrocycles by Huisgen Cycloaddition 265\u003cbr\u003e\u003ci\u003eAshok D. Pehere and Andrew D. Abell\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e11.1 Introduction 265\u003c\/p\u003e \u003cp\u003e11.2 Dipolar Cycloaddition Reactions 266\u003c\/p\u003e \u003cp\u003e11.3 Macrocyclic Peptidomimetics 267\u003c\/p\u003e \u003cp\u003e11.4 Macrocyclic β]Strand Mimetics as Cysteine Protease Inhibitors 273\u003c\/p\u003e \u003cp\u003e11.5 Conclusion 275\u003c\/p\u003e \u003cp\u003eReferences 277\u003c\/p\u003e \u003cp\u003e12 Palladium]Catalyzed Synthesis of Macrocycles 281\u003cbr\u003e\u003ci\u003eThomas O. Ronson, William P. Unsworth and Ian J. S. Fairlamb\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e12.1 Introduction 281\u003c\/p\u003e \u003cp\u003e12.2 Stille Reaction 281\u003c\/p\u003e \u003cp\u003e12.3 Suzuki– Miyaura Reaction 285\u003c\/p\u003e \u003cp\u003e12.4 Heck Reaction 288\u003c\/p\u003e \u003cp\u003e12.5 Sonogashira Reaction 290\u003c\/p\u003e \u003cp\u003e12.6 Tsuji– Trost Reaction 293\u003c\/p\u003e \u003cp\u003e12.7 Other Reactions 295\u003c\/p\u003e \u003cp\u003e12.8 Conclusion 298\u003c\/p\u003e \u003cp\u003eReferences 298\u003c\/p\u003e \u003cp\u003e13 Alternative Strategies for the Construction of Macrocycles 307\u003cbr\u003e\u003ci\u003eJeffrey Santandrea, Anne\u003c\/i\u003e\u003ci\u003e]\u003c\/i\u003e\u003ci\u003eCatherine B\u003c\/i\u003e\u003ci\u003eé\u003c\/i\u003e\u003ci\u003edard, Myl\u003c\/i\u003e\u003ci\u003eè\u003c\/i\u003e\u003ci\u003ene de L\u003c\/i\u003e\u003ci\u003eé\u003c\/i\u003e\u003ci\u003es\u003c\/i\u003e\u003ci\u003eé\u003c\/i\u003e\u003ci\u003eleuc, Micha\u003c\/i\u003e\u003ci\u003eë\u003c\/i\u003e\u003ci\u003el Raymond and Shawn K. Collins\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e13.1 Introduction 307\u003c\/p\u003e \u003cp\u003e13.2 Alternative Methods for Macrocyclization Involving Carbon–Carbon Bond Formation 307\u003c\/p\u003e \u003cp\u003e13.3 Alternative Methods for Macrocyclization Involving Carbon–Carbon Bond Formation: Ring Expansion and Photochemical Methods 320\u003c\/p\u003e \u003cp\u003e13.4 Alternative Methods for Macrocyclization Involving Carbon–Oxygen Bond Formation 322\u003c\/p\u003e \u003cp\u003e13.5 Alternative Methods for Macrocyclization Involving Carbon–Nitrogen Bond Formation 327\u003c\/p\u003e \u003cp\u003e13.6 Alternative Methods for Macrocyclization Involving Carbon–Sulfur Bond Formation 328\u003c\/p\u003e \u003cp\u003e13.7 Conclusion and Summary 331\u003c\/p\u003e \u003cp\u003eReferences 332\u003c\/p\u003e \u003cp\u003e14 Macrocycles from Multicomponent Reactions 339\u003cbr\u003e\u003ci\u003eLudger A. Wessjohann, Ricardo A. W. Neves Filho, Alfredo R. Puentes and Micjel Ch\u003c\/i\u003e\u003ci\u003eá\u003c\/i\u003e\u003ci\u003evez Morej\u003c\/i\u003e\u003ci\u003eó\u003c\/i\u003e\u003ci\u003en\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e14.1 Introduction 339\u003c\/p\u003e \u003cp\u003e14.2 General Aspects of Multicomponent Reactions (MCRs) in Macrocycle Syntheses 344\u003c\/p\u003e \u003cp\u003e14.3 Concluding Remarks and Future Perspectives 369\u003c\/p\u003e \u003cp\u003eReferences 371\u003c\/p\u003e \u003cp\u003e15 Synthetic Approaches Used in the Scale]Up of Macrocyclic Clinical Candidates 377\u003cbr\u003e\u003ci\u003eJongrock Kong\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e15.1 Introduction 377\u003c\/p\u003e \u003cp\u003e15.2 Background 377\u003c\/p\u003e \u003cp\u003e15.3 Literature Examples 378\u003c\/p\u003e \u003cp\u003e15.4 Conclusions 406\u003c\/p\u003e \u003cp\u003eReferences 406\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePart IV Macrocycles in Drug Development: Case Studies 411\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e16 Overview of Macrocycles in Clinical Development and Clinically Used 413\u003cbr\u003e\u003ci\u003eSilvia Stotani and Fabrizio Giordanetto\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e16.1 Introduction 413\u003c\/p\u003e \u003cp\u003e16.2 Datasets Generation 413\u003c\/p\u003e \u003cp\u003e16.3 Marketed Macrocyclic Drugs 414\u003c\/p\u003e \u003cp\u003e16.4 Macrocycles in Clinical Studies 422\u003c\/p\u003e \u003cp\u003e16.5 De Novo Designed Macrocycles 429\u003c\/p\u003e \u003cp\u003e16.6 Overview and Conclusions 436\u003c\/p\u003e \u003cp\u003eAppendix 16.A 437\u003c\/p\u003e \u003cp\u003e16.A.1 Methods 437\u003c\/p\u003e \u003cp\u003eReferences 490\u003c\/p\u003e \u003cp\u003e17 The Discovery of Macrocyclic IAP Inhibitors for the Treatment of Cancer 501\u003cbr\u003e\u003ci\u003eNicholas K. Terrett\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e17.1 Introduction 501\u003c\/p\u003e \u003cp\u003e17.2 DNA]Programmed Chemistry Macrocycle Libraries 502\u003c\/p\u003e \u003cp\u003e17.3 A New Macrocycle Ring Structure 504\u003c\/p\u003e \u003cp\u003e17.4 Design and Profiling of Bivalent Macrocycles 506\u003c\/p\u003e \u003cp\u003e17.5 Improving the Profile of the Bivalent Macrocycles 510\u003c\/p\u003e \u003cp\u003e17.6 Selection of the Optimal Bivalent Macrocyclic IAP Antagonist 512\u003c\/p\u003e \u003cp\u003e17.7 Summary 515\u003c\/p\u003e \u003cp\u003eAcknowledgments 515\u003c\/p\u003e \u003cp\u003eReferences 516\u003c\/p\u003e \u003cp\u003e18 Discovery and Pharmacokinetic–Pharmacodynamic Evaluation of an Orally Available Novel Macrocyclic Inhibitor of Anaplastic Lymphoma Kinase and c]Ros Oncogene 1 519\u003cbr\u003e\u003ci\u003eShinji Yamazaki, Justine L. Lam and Ted W. Johnson\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e18.1 Introduction 519\u003c\/p\u003e \u003cp\u003e18.2 Discovery and Synthesis 520\u003c\/p\u003e \u003cp\u003e18.3 Evaluation of Pharmacokinetic Properties Including CNS Penetration 531\u003c\/p\u003e \u003cp\u003e18.4 Evaluation of Pharmacokinetic–Pharmacodynamic (PKPD) Profiles 536\u003c\/p\u003e \u003cp\u003e18.5 Conclusion 540\u003c\/p\u003e \u003cp\u003eReferences 540\u003c\/p\u003e \u003cp\u003e19 Optimization of a Macrocyclic Ghrelin Receptor Agonist (Part II): Development of TZP]102 545\u003cbr\u003e\u003ci\u003eHamid R. Hoveyda, Graeme L. Fraser, Eric Marsault, Ren\u003c\/i\u003e\u003ci\u003eé\u003c\/i\u003e\u003ci\u003e Gagnon and Mark L. Peterson\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e19.1 Introduction 545\u003c\/p\u003e \u003cp\u003e19.2 Advanced AA3 and Tether SAR 548\u003c\/p\u003e \u003cp\u003e19.3 Structural Studies 554\u003c\/p\u003e \u003cp\u003e19.4 Conclusions 554\u003c\/p\u003e \u003cp\u003eAcknowledgments 555\u003c\/p\u003e \u003cp\u003eReferences 556\u003c\/p\u003e \u003cp\u003e20 Solithromycin: Fourth]Generation Macrolide Antibiotic 559\u003cbr\u003e\u003ci\u003eDavid Pereira, Sara Wu, Shingai Majuru, Stephen E. Schneider and Lovy Pradeep\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e20.1 Introduction 559\u003c\/p\u003e \u003cp\u003e20.2 Structure–Activity Relationship (SAR) of Ketolides and Selection of Solithromycin 559\u003c\/p\u003e \u003cp\u003e20.3 Mechanism of Action 564\u003c\/p\u003e \u003cp\u003e20.4 Overcoming the Ketek Effect 568\u003c\/p\u003e \u003cp\u003e20.5 Manufacture of Solithromycin 569\u003c\/p\u003e \u003cp\u003e20.6 Polymorphism 569\u003c\/p\u003e \u003cp\u003e20.7 Pharmaceutical Development 569\u003c\/p\u003e \u003cp\u003e20.8 Clinical Data 574\u003c\/p\u003e \u003cp\u003e20.9 Summary 574\u003c\/p\u003e \u003cp\u003eReferences 574\u003c\/p\u003e \u003cp\u003eIndex 579\u003c\/p\u003e \u003cp\u003e \u003c\/p\u003e","brand":"John Wiley \u0026 Sons Inc","offers":[{"title":"Default Title","offer_id":49528846680407,"sku":"9781119092568","price":177.6,"currency_code":"GBP","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0817\/1739\/5799\/files\/9781119092568.jpg?v=1731873254","url":"https:\/\/bookcurl.com\/products\/practical-medicinal-chemistry-with-macrocycles-9781119092568","provider":"Book Curl","version":"1.0","type":"link"}