{"product_id":"peptidomimetics-in-organic-and-medicinal-chemistry-9781119950608","title":"Peptidomimetics in Organic and Medicinal","description":"\u003cb\u003eBook Synopsis\u003c\/b\u003e\u003cbr\u003e\u003cp\u003eA peptidomimetic is a small protein-like chain designed to mimic a peptide with adjusted molecular properties such as enhanced stability or biological activity. It is a very powerful approach for the generation of small-molecule-based drugs as enzyme inhibitors or receptor ligands.\u003c\/p\u003e \u003cp\u003e\u003ci\u003ePeptidomimetics in Organic and Medicinal Chemistry\u003c\/i\u003e outlines the concepts and synthetic strategies underlying the building of bioactive compounds of a peptidomimetic nature. Topics covered include the chemistry of unnatural amino acids, peptide- and scaffold-based peptidomimetics, amino acid-side chain isosteres, backbone isosteres, dipeptide isosteres, beta-turn peptidomimetics, proline-mimetics as turn inducers, cyclic scaffolds, amino acid surrogates, and scaffolds for combinatorial chemistry of peptidomimetics. Case studies in the hit-to-lead process, such as the development of integrin ligands and thrombin inhibitors, illustrate the successful application of peptidomimetics in drug disco\u003cbr\u003e\u003cbr\u003e\u003cb\u003eTable of Contents\u003c\/b\u003e\u003cbr\u003ePreface xiii  \u003c\/p\u003e\u003cp\u003eAbbreviations xvii\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePART I The Basics of Peptidomimetics 1\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e1. The Basics of Peptidomimetics 3\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e1.1 Introduction 3\u003c\/p\u003e \u003cp\u003e1.2 Definition and Classification 5\u003c\/p\u003e \u003cp\u003e1.3 Strategic Approaches to Peptidomimetic Design 7\u003c\/p\u003e \u003cp\u003e1.3.1 Modification of Amino Acids 8\u003c\/p\u003e \u003cp\u003e1.3.2 Compounds with Global Restrictions 9\u003c\/p\u003e \u003cp\u003e1.3.3 Molecular Scaffolds Mimicking the Peptidic Backbone 10\u003c\/p\u003e \u003cp\u003e1.4 Successful Examples of Peptidomimetic Drugs 12\u003c\/p\u003e \u003cp\u003e1.4.1 ACE Inhibitors 13\u003c\/p\u003e \u003cp\u003e1.4.2 Thrombin Inhibitors 13\u003c\/p\u003e \u003cp\u003e1.5 Conclusion 16\u003c\/p\u003e \u003cp\u003eReferences 16\u003c\/p\u003e \u003cp\u003e\u003cb\u003e2. Synthetic Approaches towards Peptidomimetic Design 19\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e2.1 Introduction 19\u003c\/p\u003e \u003cp\u003e2.2 Local Modifications 20\u003c\/p\u003e \u003cp\u003e2.2.1 Single Amino Acid Modifications 23\u003c\/p\u003e \u003cp\u003e2.2.2 Dipeptide Isosteres 26\u003c\/p\u003e \u003cp\u003e2.2.3 Retro-inverso Peptides 29\u003c\/p\u003e \u003cp\u003e2.2.4 N-Methylation of Peptides 30\u003c\/p\u003e \u003cp\u003e2.2.5 Azapeptides 31\u003c\/p\u003e \u003cp\u003e2.2.6 Peptoids 31\u003c\/p\u003e \u003cp\u003e2.3 Global Restrictions through Cyclic Peptidomimetics 32\u003c\/p\u003e \u003cp\u003e2.4 Peptidomimetic Scaffolds 34\u003c\/p\u003e \u003cp\u003e2.5 Conclusions 35\u003c\/p\u003e \u003cp\u003eReferences 35\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePART II Synthetic Methods and Molecules 37\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e3. Peptidomimetic Bioisosteres 39\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e3.1 Introduction 39\u003c\/p\u003e \u003cp\u003e3.2 Peptide Bond Isosteres 40\u003c\/p\u003e \u003cp\u003e3.2.1 Thioamides 41\u003c\/p\u003e \u003cp\u003e3.2.2 Esters 41\u003c\/p\u003e \u003cp\u003e3.2.3 Alkenes and Fluoroalkenes 41\u003c\/p\u003e \u003cp\u003e3.2.4 Transition-State Isosteres 42\u003c\/p\u003e \u003cp\u003e3.3 Side-Chain Isosteres 45\u003c\/p\u003e \u003cp\u003e3.3.1 Guanidine Isosteres in Arginine Peptidomimetics 45\u003c\/p\u003e \u003cp\u003e3.3.2 Isosteres of Aspartic Acid and Glutamic Acid 49\u003c\/p\u003e \u003cp\u003e3.3.3 Tethered α-Amino Acids: Constraining the χ-Space 53\u003c\/p\u003e \u003cp\u003e3.4 Dipeptide Isosteres 59\u003c\/p\u003e \u003cp\u003e3.4.1 δ-Amino Acids 63\u003c\/p\u003e \u003cp\u003e3.5 Tripeptide Isosteres 67\u003c\/p\u003e \u003cp\u003e3.6 Conclusion 68\u003c\/p\u003e \u003cp\u003eReferences 69\u003c\/p\u003e \u003cp\u003e\u003cb\u003e4. Solid-Phase Synthesis and Combinatorial Approaches to Peptidomimetics 75\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e4.1 Introduction 75\u003c\/p\u003e \u003cp\u003e4.2 Solid-Phase Synthesis of Peptidomimetics 76\u003c\/p\u003e \u003cp\u003e4.2.1 Scaffolds from α-Amino Acids 76\u003c\/p\u003e \u003cp\u003e4.2.2 Scaffolds from Amino Aldehyde Intermediates 85\u003c\/p\u003e \u003cp\u003e4.2.3 Pyrrolidine-Containing Scaffolds 89\u003c\/p\u003e \u003cp\u003e4.3 Conclusion 94\u003c\/p\u003e \u003cp\u003eReferences 95\u003c\/p\u003e \u003cp\u003e\u003cb\u003e5. Click Chemistry: The Triazole Ring as a Privileged Peptidomimetic Scaffold 99\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e5.1 Introduction 99\u003c\/p\u003e \u003cp\u003e5.1.1 CuAAC Reaction 100\u003c\/p\u003e \u003cp\u003e5.1.2 Triazole Ring as a Peptidomimetic Isostere 101\u003c\/p\u003e \u003cp\u003e5.2 Triazole-Containing Peptidomimetics Elaborated through ‘Click Chemistry’ 102\u003c\/p\u003e \u003cp\u003e5.2.1 Macrocycles 102\u003c\/p\u003e \u003cp\u003e5.2.2 Oligomers and Foldamers 107\u003c\/p\u003e \u003cp\u003e5.3 Relevant Applications in Drug Discovery 110\u003c\/p\u003e \u003cp\u003e5.3.1 AChE Inhibitors 110\u003c\/p\u003e \u003cp\u003e5.3.2 HIV Protease Inhibitors 111\u003c\/p\u003e \u003cp\u003e5.3.3 MMP Inhibitors 114\u003c\/p\u003e \u003cp\u003e5.3.4 Integrin Ligands 115\u003c\/p\u003e \u003cp\u003e5.4 Conclusions 118\u003c\/p\u003e \u003cp\u003eAcknowledgements 119\u003c\/p\u003e \u003cp\u003eReferences 119\u003c\/p\u003e \u003cp\u003e\u003cb\u003e6. Peptoids 123\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e6.1 Introduction and Basics of Peptoids 123\u003c\/p\u003e \u003cp\u003e6.2 Synthetic Methods 126\u003c\/p\u003e \u003cp\u003e6.3 Macrocyclic Peptoids 129\u003c\/p\u003e \u003cp\u003e6.4 Conformational Analysis of Folded Peptoids 130\u003c\/p\u003e \u003cp\u003e6.5 Application of Peptoids as Antimicrobial Peptidomimetics 132\u003c\/p\u003e \u003cp\u003e6.6 Conclusions 134\u003c\/p\u003e \u003cp\u003eReferences 134\u003c\/p\u003e \u003cp\u003e\u003cb\u003e7. Sugar Amino Acids 137\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e7.1 Introduction 137\u003c\/p\u003e \u003cp\u003e7.2 α-SAAs 138\u003c\/p\u003e \u003cp\u003e7.2.1 Furanoid α-SAAs 138\u003c\/p\u003e \u003cp\u003e7.2.2 Pyranoid α-SAAs 142\u003c\/p\u003e \u003cp\u003e7.3 β-SAAs 144\u003c\/p\u003e \u003cp\u003e7.3.1 Furanoid β-SAAs 144\u003c\/p\u003e \u003cp\u003e7.3.2 Pyranoid β-SAAs 147\u003c\/p\u003e \u003cp\u003e7.4 γ-SAAs 148\u003c\/p\u003e \u003cp\u003e7.5 δ-SAAs 150\u003c\/p\u003e \u003cp\u003e7.5.1 Furanoid δ-SAAs 150\u003c\/p\u003e \u003cp\u003e7.5.2 Pyranoid δ-SAAs 154\u003c\/p\u003e \u003cp\u003e7.6 Representative Applications in Medicinal Chemistry 159\u003c\/p\u003e \u003cp\u003e7.7 Conclusions 162\u003c\/p\u003e \u003cp\u003eReferences 162\u003c\/p\u003e \u003cp\u003e\u003cb\u003e8. Cyclic -Amino Acids as Proline Mimetics 165\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e8.1 Introduction 165\u003c\/p\u003e \u003cp\u003e8.2 Cyclic α-Amino Acids 166\u003c\/p\u003e \u003cp\u003e8.2.1 3-Substituted Proline Derivatives 167\u003c\/p\u003e \u003cp\u003e8.2.2 4-Substituted Proline Derivatives 168\u003c\/p\u003e \u003cp\u003e8.2.3 5-Substituted Proline Derivatives 169\u003c\/p\u003e \u003cp\u003e8.2.4 Other Heterocyclic Proline Analogues 171\u003c\/p\u003e \u003cp\u003e8.3 Bicyclic α-Amino Acids 174\u003c\/p\u003e \u003cp\u003e8.3.1 β\/γ-Ring Junction 175\u003c\/p\u003e \u003cp\u003e8.3.2 α\/γ-Ring Junction 178\u003c\/p\u003e \u003cp\u003e8.3.3 γ\/δ-Ring Junction 179\u003c\/p\u003e \u003cp\u003e8.3.4 α\/δ-Ring Junction 180\u003c\/p\u003e \u003cp\u003e8.3.5 β\/δ-Ring Junction 182\u003c\/p\u003e \u003cp\u003e8.3.6 N\/β-Ring Junction 183\u003c\/p\u003e \u003cp\u003e8.3.7 Pipecolic-Based Bicyclic α-Amino Acids 183\u003c\/p\u003e \u003cp\u003e8.3.8 Morpholine-Based Bicyclic α-Amino Acids 187\u003c\/p\u003e \u003cp\u003e8.4 Conclusions 189\u003c\/p\u003e \u003cp\u003eReferences 189\u003c\/p\u003e \u003cp\u003e\u003cb\u003e9. -Turn Peptidomimetics 191\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e9.1 Introduction 191\u003c\/p\u003e \u003cp\u003e9.2 Definition and Classification of β-Turns 192\u003c\/p\u003e \u003cp\u003e9.3 Conformational Analysis 194\u003c\/p\u003e \u003cp\u003e9.4 β-Turn Peptidomimetics 196\u003c\/p\u003e \u003cp\u003e9.4.1 Proline Analogues in β-Turn Peptidomimetics 197\u003c\/p\u003e \u003cp\u003e9.4.2 δ-Amino Acids as Reverse-Turn Inducers 200\u003c\/p\u003e \u003cp\u003e9.4.3 Molecular Scaffolds as β-Turn Peptidomimetics 209\u003c\/p\u003e \u003cp\u003e9.5 Conclusions 214\u003c\/p\u003e \u003cp\u003eReferences 215\u003c\/p\u003e \u003cp\u003e\u003cb\u003e10. Peptidomimetic Foldamers 219\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e10.1 Introduction 219\u003c\/p\u003e \u003cp\u003e10.2 Classification 220\u003c\/p\u003e \u003cp\u003e10.3 Peptoids 221\u003c\/p\u003e \u003cp\u003e10.4 β-Peptides: First Systematic Conformational Studies 221\u003c\/p\u003e \u003cp\u003e10.5 Hybrid Foldamers 226\u003c\/p\u003e \u003cp\u003e10.6 From Structural to Functional Foldamers 227\u003c\/p\u003e \u003cp\u003e10.6.1 Peptoids as Foldameric Antimicrobial Peptidomimetics 227\u003c\/p\u003e \u003cp\u003e10.6.2 Foldamers Targeting Bcl-xL Antiapoptotic Proteins 227\u003c\/p\u003e \u003cp\u003e10.7 Conclusions 228\u003c\/p\u003e \u003cp\u003eReferences 228\u003c\/p\u003e \u003cp\u003e\u003cb\u003ePART III Applications in Medicinal Chemistry 231\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e11. Case Study 1: Peptidomimetic HIV Protease Inhibitors 233\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e11.1 Introduction 233\u003c\/p\u003e \u003cp\u003e11.2 The HIV-1 Virus 233\u003c\/p\u003e \u003cp\u003e11.2.1 HIV-1 Protease 234\u003c\/p\u003e \u003cp\u003e11.3 Antiretroviral Therapy 238\u003c\/p\u003e \u003cp\u003e11.4 Drug Resistance 239\u003c\/p\u003e \u003cp\u003e11.4.1 Mechanisms of Resistance to Protease Inhibitors 239\u003c\/p\u003e \u003cp\u003e11.5 HIV-1 Protease Inhibitors 240\u003c\/p\u003e \u003cp\u003e11.5.1 Transition-State Analogues 240\u003c\/p\u003e \u003cp\u003e11.5.2 Peptidomimetic Drugs 241\u003c\/p\u003e \u003cp\u003e11.5.3 Next-Generation Cyclic Peptidomimetic Inhibitors 245\u003c\/p\u003e \u003cp\u003e11.6 Conclusions 255\u003c\/p\u003e \u003cp\u003eAcknowledgements 255\u003c\/p\u003e \u003cp\u003eReferences 256\u003c\/p\u003e \u003cp\u003e\u003cb\u003e12. Case Study 2: Peptidomimetic Ligands for  Integrin 259\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e12.1 Introduction 259\u003c\/p\u003e \u003cp\u003e12.2 Peptide-Based Peptidomimetic Integrin Ligands 262\u003c\/p\u003e \u003cp\u003e12.3 Scaffold-Based Peptidomimetic Integrin Ligands 270\u003c\/p\u003e \u003cp\u003e12.4 Conclusions 280\u003c\/p\u003e \u003cp\u003eReferences 280\u003c\/p\u003e \u003cp\u003eIndex 283\u003c\/p\u003e","brand":"John Wiley \u0026 Sons Inc","offers":[{"title":"Default Title","offer_id":49528867455319,"sku":"9781119950608","price":117.95,"currency_code":"GBP","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0817\/1739\/5799\/files\/9781119950608.jpg?v=1731873338","url":"https:\/\/bookcurl.com\/products\/peptidomimetics-in-organic-and-medicinal-chemistry-9781119950608","provider":"Book Curl","version":"1.0","type":"link"}