Privileged structures in drug discovery : medicinal chemistry and synthesis /: medicinal chemistry and synthesis. (2017)

• Record Type: Book
• Further Information: Note: Larry Yet.
• Authors: Yet, Larry
• Contents: 1 Introduction 1 1.1 The Original Definition of Privileged Structures 1 1.2 The Role of Privileged Structures in the Drug Discovery Process 1 1.3 The Loose Definitions of “Privileged Structures” 2 1.4 Synthesis and Biological Activities of Carbocyclic and Heterocyclic Privileged Structures 2 1.4.1 Synthesis and Biological Activities of Three?] and Four?]Membered Ring Privileged Structures 2 1.4.2 Synthesis and Biological Activities of Five-Membered Ring Privileged Structures 2 1.4.3 Synthesis and Biological Activities of Six-Membered Ring Privileged Structures 4 1.4.4 Synthesis and Biological Activities of Bicyclic 5/5 and 6/5 Ring Privileged Structures 4 1.4.5 Synthesis and Biological Activities of Bicyclic 6/6 and 6/7 Ring Privileged Structures 4 1.4.6 Synthesis and Biological Activities of Tricyclic and Tetracyclic Ring Privileged Structures 4 1.5 Combinatorial Libraries of “Privileged Structures” 4 1.6 Scope of this Monograph 9 References 10 2 Benzodiazepines 15 2.1 Introduction 15 2.2 Marketed BDZ Drugs 15 2.2.1 1, 4-Benzodiazepine Marketed Drugs 15 2.2.2 1, 5-Benzodiazepine Marketed Drugs 16 2.2.3 Linearly Fused BDZ Marketed Drugs 16 2.2.4 Angularly Fused-1, 4-Benzodiazepine Marketed Drugs 17 2.3 Medicinal Chemistry Case Studies 17 2.3.1 Cardiovascular Applications 17 2.3.2 Central Nervous System Applications 19 2.3.3 Gastrointestinal Applications 23 2.3.4 Infectious Diseases Applications 24 2.3.5 Inflammation Applications 25 2.3.6 Metabolic Diseases Applications 27 2.3.7 Oncology Applications 28 2.4 Synthesis of BDZs 30 2.4.1 Condensation of o-Phenylenediamines to 1, 5-Benzodiazepines 31 2.4.1.1 Condensation of o-Phenylenediamines with Ketones 31 2.4.1.2 Condensation of o-Phenylenediamines with α, β-Unsaturated Ketones 33 2.4.1.3 Condensation of o-Phenylenediamines with Alkynes 34 2.4.2 Reductive Condensation of α-Substituted Nitrobenzenes with Ketones and α, β-Unsaturated Ketones 35 2.4.3 Intramolecular Cyclizations to 1, 4-Benzodiazepines 35 2.4.3.1 Intramolecular Cyclizations—Path A 36 2.4.3.2 Intramolecular Cyclizations—Path B 37 2.4.3.3 Intramolecular Cyclizations—Path C 39 2.4.3.4 Intramolecular Cyclizations—Path D 40 2.4.3.5 Intramolecular Cyclizations—Path E 42 2.4.3.6 Intramolecular Cyclizations—Path F 42 2.4.3.7 Intramolecular Cyclizations—Path G 42 2.4.3.8 Intramolecular Cyclizations—Path H 42 2.4.4 Ugi Multicomponent Synthesis 42 2.4.5 Elaboration of 1, 4-Benzodiazepines 44 2.4.6 Pyrrolo[2, 1-c]benzodiazepines 45 2.4.7 Fused BDZ Ring Systems 45 2.4.8 Solid-Phase Synthesis of BDZs 47 References 47 3 1, 4-Dihydropyridines 59 3.1 Introduction 59 3.2 Marketed 1, 4-Dihyropyridine Drugs 59 3.3 Medicinal Chemistry Case Studies 59 3.3.1 Cardiovascular Applications 59 3.3.2 Central Nervous System Applications 61 3.3.3 Infectious Diseases Applications 62 3.3.4 Inflammation Applications 63 3.3.5 Men’s and Women’s Health Issues Applications 64 3.3.6 Metabolic Diseases Applications 65 3.3.7 Oncology Applications 65 3.4 Synthesis of 1, 4-Dihydropyridines 66 3.4.1 Classical Hantzsch Synthesis 66 3.4.2 Modified Hantzsch Conditions 66 3.4.3 1, 4-Disubstituted-1, 4-Dihydropyridines 69 3.4.4 Organometallic Additions to Pyridinium Salts 69 3.4.5 From Imines and Enamino Compounds 71 3.4.6 Multicomponent Synthesis 72 3.4.6.1 Three-Component Synthesis of 1, 4-Dihydropyridines 72 3.4.6.2 Four-Component Synthesis of 1, 4-Dihydropyridines 74 3.4.7 Organocatalytic Synthesis of 1, 4-Dihydropyridines 74 3.4.8 Miscellaneous Preparations 75 3.4.9 Elaboration of 1, 4-Dihydropyridines 76 References 77 4 Biaryls 83 4.1 Introduction 83 4.2 Marketed Biaryl Drugs 83 4.3 Medicinal Chemistry Case Studies 87 4.3.1 Cardiovascular Applications 87 4.3.2 Central Nervous System Applications 89 4.3.3 Infectious Diseases Applications 95 4.3.4 Inflammation Applications 98 4.3.5 Men’s and Women’s Health Issues Applications 102 4.3.6 Metabolic Diseases Applications 103 4.3.7 Oncology Applications 109 4.4 Synthesis of Biaryls 114 4.4.1 Transition Metal-Catalyzed Cross‑Coupling Synthesis 114 4.4.1.1 Suzuki–Miyaura Cross-Coupling Reactions with Boronic Acids 114 4.4.1.2 Suzuki–Miyaura Cross-Coupling Reactions with Boronate Esters 114 4.4.1.3 Metal-Catalyzed Homocoupling Reactions 121 4.4.1.4 Uhlmann Coupling Reactions 122 4.4.1.5 Kumada–Tamao–Corriu Cross-Coupling Reactions 123 4.4.1.6 Negishi Cross-Coupling Reactions 124 4.4.1.7 Hiyama Cross-Coupling Reactions 124 4.4.1.8 Stille Cross-Coupling Reactions 125 4.4.1.9 Miscellaneous Cross-Coupling Reactions 126 4.4.1.10 Metal-Catalyzed Functional Group Removal Cross-Coupling Reaction 127 4.4.2 C„ŸH Functionalization Reactions 127 4.4.2.1 Oxidative Coupling Reactions 127 4.4.2.2 Direct C„ŸH Arylations 127 4.4.2.3 C„ŸH Functionalization with Directing Groups 127 4.4.3 Cycloaddition Reactions 132 4.4.3.1 [3+3] Cycloaddition Reactions 132 4.4.3.2 [4+2] Cycloaddition Reactions 132 4.4.3.3 [2+2+2] Cycloaddition Reactions 133 4.4.3.4 Tandem Cycloaddition Reactions 133 4.4.4 Biaryl Phenol Syntheses 133 4.4.5 Miscellaneous Syntheses 134 References 135 5 4-(Hetero)Arylpiperidines 155 5.1 Introduction 155 5.2 Marketed 4-(Hetero)Arylpiperidine Drugs 155 5.3 Medicinal Chemistry Case Studies 159 5.3.1 Cardiovascular Applications 159 5.3.2 Central Nervous System Applications 159 5.3.3 Infectious Diseases Applications 168 5.3.4 Inflammation Applications 169 5.3.5 Men’s and Women’s Health Applications 174 5.3.6 Metabolic Diseases Applications 175 5.3.7 Oncology Applications 177 5.4 Synthesis of 4-(Hetero)Arylpiperidines 179 5.4.1 Preparation from 4-Piperidinones 179 5.4.2 Preparation from 4-Prefunctionalized-3-alkenylpiperidines 180 5.4.3 Preparation from Negishi Cross-Coupling of 3-Zincated Piperidines 180 5.4.4 Preparation from 4-Funtionalized Piperidines 181 5.4.5 Conjugated Addition to Unsaturated Piperidines 181 5.4.6 Miscellaneous Syntheses 183 References 185 6 Spiropiperidines 194 6.1 Introduction 194 6.2 Marketed Spiropiperidine Drugs 194 6.3 Medicinal Chemistry Case Studies 195 6.3.1 Cardiovascular Applications 195 6.3.2 Central Nervous System Applications 197 6.3.3 Infectious Diseases Applications 203 6.3.4 Inflammation Applications 205 6.3.5 Men’s and Women’s Health Applications 210 6.3.6 Metabolic Diseases Applications 211 6.3.7 Oncology Applications 216 6.4 Synthesis of Spiropiperidines 218 6.4.1 Quinolinylspiropiperidines 218 0003364809.INDD 7 12/18/2017 9:40:53 PM viii Contents 6.4.2 Azaspiro[5.5]alkane Systems 218 6.4.3 Diazaspiro[5.5]alkane Derivatives 221 6.4.4 1, 4-Benzodioxinylspiropiperidines 222 6.4.5 Spirobenzooxazinylspiropiperidines 223 6.4.6 (Iso)Quinolinylspiropiperidines 223 6.4.7 Indenospiropiperidines 225 6.4.8 Indolin(on)ylspiropiperidines 225 6.4.9 Cyclohexadienonylspiropiperidines 226 6.4.10 Cyclopenta[b]pyrrolospiropiperidines 226 6.4.11 Chromanylspiropiperidines 226 6.4.12 (Iso)Benzofuran(on)ylspiropiperidines 227 6.4.13
• Edition: 1st
• Publisher Details: Hoboken, New Jersey : John Wiley & Sons, Inc
• Publication Date: 2017
• Extent: 1 online resource
• Subjects: 615.19; Drug development
• Languages: English
• ISBNs: 9781118686331
• Related ISBNs: 9781118686355
• Notes: Note: Description based on CIP data; resource not viewed.
• Access Rights: Legal Deposit; Only available on premises controlled by the deposit library and to one user at any one time; The Legal Deposit Libraries (Non-Print Works) Regulations (UK).
• Access Usage: Restricted: Printing from this resource is governed by The Legal Deposit Libraries (Non-Print Works) Regulations (UK) and UK copyright law currently in force.