Details

Privileged Structures in Drug Discovery


Privileged Structures in Drug Discovery

Medicinal Chemistry and Synthesis
1. Aufl.

von: Larry Yet

164,99 €

Verlag: Wiley
Format: PDF
Veröffentl.: 07.03.2018
ISBN/EAN: 9781118686355
Sprache: englisch
Anzahl Seiten: 560

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Beschreibungen

<p><b>A comprehensive guide to privileged structures and their application in the discovery of new drugs</b><b> </b></p> <p>The use of privileged structures is a viable strategy in the discovery of new medicines at the lead optimization stages of the drug discovery process.  <i>Privileged Structures in Drug Discovery</i> offers a comprehensive text that reviews privileged structures from the point of view of medicinal chemistry and contains the synthetic routes to these structures. In this text, the author—a noted expert in the field—includes an historical perspective on the topic, presents a practical compendium to privileged structures, and offers an informed perspective on the future direction for the field.</p> <p>The book describes the up-to-date and state-of-the-art methods of organic synthesis that describe the use of privileged structures that are of most interest. Chapters included information on benzodiazepines, 1,4-dihydropyridines, biaryls, 4-(hetero)arylpiperidines, spiropiperidines, 2-aminopyrimidines, 2-aminothiazoles, 2-(hetero)arylindoles, tetrahydroisoquinolines,  2,2-dimethylbenzopyrans, hydroxamates, and bicyclic pyridines containing ring-junction nitrogen as privileged scaffolds in medicinal chemistry. Numerous, illustrative case studies document the current use of the privileged structures in the discovery of drugs. This important volume:</p> <ul> <li>Describes the drug compounds that have successfully made it to the marketplace and the chemistry associated with them</li> <li>Offers the experience from an author who has worked in many therapeutic areas of medicinal chemistry</li> <li>Details many of the recent developments in organic chemistry that prepare target molecules</li> <li>Includes a wealth of medicinal chemistry case studies that clearly illustrate the use of privileged structures</li> </ul> <p>Designed for use by industrial medicinal chemists and process chemists, academic organic and medicinal chemists, as well as chemistry students and faculty, <i>Privileged Structures in Drug Discovery </i>offers a current guide to organic synthesis methods to access the privileged structures of interest, and contains medicinal chemistry case studies that document their application.</p>
<p><b>1 Introduction 1</b></p> <p>1.1 The Original Definition of Privileged Structures 1</p> <p>1.2 The Role of Privileged Structures in the Drug Discovery Process 1</p> <p>1.3 The Loose Definitions of “Privileged Structures” 2</p> <p>1.4 Synthesis and Biological Activities of Carbocyclic and Heterocyclic Privileged Structures 2</p> <p>1.4.1 Synthesis and Biological Activities of Three?] and Four?]Membered Ring Privileged Structures 2</p> <p>1.4.2 Synthesis and Biological Activities of Five-Membered Ring Privileged Structures 2</p> <p>1.4.3 Synthesis and Biological Activities of Six-Membered Ring Privileged Structures 4</p> <p>1.4.4 Synthesis and Biological Activities of Bicyclic 5/5 and 6/5 Ring Privileged Structures 4</p> <p>1.4.5 Synthesis and Biological Activities of Bicyclic 6/6 and 6/7 Ring Privileged Structures 4</p> <p>1.4.6 Synthesis and Biological Activities of Tricyclic and Tetracyclic Ring Privileged Structures 4</p> <p>1.5 Combinatorial Libraries of “Privileged Structures” 4</p> <p>1.6 Scope of this Monograph 9</p> <p>References 10</p> <p><b>2 Benzodiazepines 15</b></p> <p>2.1 Introduction 15</p> <p>2.2 Marketed BDZ Drugs 15</p> <p>2.2.1 1,4-Benzodiazepine Marketed Drugs 15</p> <p>2.2.2 1,5-Benzodiazepine Marketed Drugs 16</p> <p>2.2.3 Linearly Fused BDZ Marketed Drugs 16</p> <p>2.2.4 Angularly Fused-1,4-Benzodiazepine Marketed Drugs 17</p> <p>2.3 Medicinal Chemistry Case Studies 17</p> <p>2.3.1 Cardiovascular Applications 17</p> <p>2.3.2 Central Nervous System Applications 19</p> <p>2.3.3 Gastrointestinal Applications 23</p> <p>2.3.4 Infectious Diseases Applications 24</p> <p>2.3.5 Inflammation Applications 25</p> <p>2.3.6 Metabolic Diseases Applications 27</p> <p>2.3.7 Oncology Applications 28</p> <p>2.4 Synthesis of BDZs 30</p> <p>2.4.1 Condensation of o-Phenylenediamines to 1,5-Benzodiazepines 31</p> <p>2.4.1.1 Condensation of o-Phenylenediamines with Ketones 31</p> <p>2.4.1.2 Condensation of o-Phenylenediamines with α,β-Unsaturated Ketones 33</p> <p>2.4.1.3 Condensation of o-Phenylenediamines with Alkynes 34</p> <p>2.4.2 Reductive Condensation of α-Substituted Nitrobenzenes with Ketones and α,β-Unsaturated Ketones 35</p> <p>2.4.3 Intramolecular Cyclizations to 1,4-Benzodiazepines 35</p> <p>2.4.3.1 Intramolecular Cyclizations—Path A 36</p> <p>2.4.3.2 Intramolecular Cyclizations—Path B 37</p> <p>2.4.3.3 Intramolecular Cyclizations—Path C 39</p> <p>2.4.3.4 Intramolecular Cyclizations—Path D 40</p> <p>2.4.3.5 Intramolecular Cyclizations—Path E 42</p> <p>2.4.3.6 Intramolecular Cyclizations—Path F 42</p> <p>2.4.3.7 Intramolecular Cyclizations—Path G 42</p> <p>2.4.3.8 Intramolecular Cyclizations—Path H 42</p> <p>2.4.4 Ugi Multicomponent Synthesis 42</p> <p>2.4.5 Elaboration of 1,4-Benzodiazepines 44</p> <p>2.4.6 Pyrrolo[2,1-c]benzodiazepines 45</p> <p>2.4.7 Fused BDZ Ring Systems 45</p> <p>2.4.8 Solid-Phase Synthesis of BDZs 47</p> <p>References 47</p> <p><b>3 1,4-Dihydropyridines 59</b></p> <p>3.1 Introduction 59</p> <p>3.2 Marketed 1,4-Dihyropyridine Drugs 59</p> <p>3.3 Medicinal Chemistry Case Studies 59</p> <p>3.3.1 Cardiovascular Applications 59</p> <p>3.3.2 Central Nervous System Applications 61</p> <p>3.3.3 Infectious Diseases Applications 62</p> <p>3.3.4 Inflammation Applications 63</p> <p>3.3.5 Men’s and Women’s Health Issues Applications 64</p> <p>3.3.6 Metabolic Diseases Applications 65</p> <p>3.3.7 Oncology Applications 65</p> <p>3.4 Synthesis of 1,4-Dihydropyridines 66</p> <p>3.4.1 Classical Hantzsch Synthesis 66</p> <p>3.4.2 Modified Hantzsch Conditions 66</p> <p>3.4.3 1,4-Disubstituted-1,4-Dihydropyridines 69</p> <p>3.4.4 Organometallic Additions to Pyridinium Salts 69</p> <p>3.4.5 From Imines and Enamino Compounds 71</p> <p>3.4.6 Multicomponent Synthesis 72</p> <p>3.4.6.1 Three-Component Synthesis of 1,4-Dihydropyridines 72</p> <p>3.4.6.2 Four-Component Synthesis of 1,4-Dihydropyridines 74</p> <p>3.4.7 Organocatalytic Synthesis of 1,4-Dihydropyridines 74</p> <p>3.4.8 Miscellaneous Preparations 75</p> <p>3.4.9 Elaboration of 1,4-Dihydropyridines 76</p> <p>References 77</p> <p><b>4 Biaryls 83</b></p> <p>4.1 Introduction 83</p> <p>4.2 Marketed Biaryl Drugs 83</p> <p>4.3 Medicinal Chemistry Case Studies 87</p> <p>4.3.1 Cardiovascular Applications 87</p> <p>4.3.2 Central Nervous System Applications 89</p> <p>4.3.3 Infectious Diseases Applications 95</p> <p>4.3.4 Inflammation Applications 98</p> <p>4.3.5 Men’s and Women’s Health Issues Applications 102</p> <p>4.3.6 Metabolic Diseases Applications 103</p> <p>4.3.7 Oncology Applications 109</p> <p>4.4 Synthesis of Biaryls 114</p> <p>4.4.1 Transition Metal-Catalyzed Cross‑Coupling Synthesis 114</p> <p>4.4.1.1 Suzuki–Miyaura Cross-Coupling Reactions with Boronic Acids 114</p> <p>4.4.1.2 Suzuki–Miyaura Cross-Coupling Reactions with Boronate Esters 114</p> <p>4.4.1.3 Metal-Catalyzed Homocoupling Reactions 121</p> <p>4.4.1.4 Uhlmann Coupling Reactions 122</p> <p>4.4.1.5 Kumada–Tamao–Corriu Cross-Coupling Reactions 123</p> <p>4.4.1.6 Negishi Cross-Coupling Reactions 124</p> <p>4.4.1.7 Hiyama Cross-Coupling Reactions 124</p> <p>4.4.1.8 Stille Cross-Coupling Reactions 125</p> <p>4.4.1.9 Miscellaneous Cross-Coupling Reactions 126</p> <p>4.4.1.10 Metal-Catalyzed Functional Group Removal Cross-Coupling Reaction 127</p> <p>4.4.2 C„ŸH Functionalization Reactions 127</p> <p>4.4.2.1 Oxidative Coupling Reactions 127</p> <p>4.4.2.2 Direct C„ŸH Arylations 127</p> <p>4.4.2.3 C„ŸH Functionalization with Directing Groups 127</p> <p>4.4.3 Cycloaddition Reactions 132</p> <p>4.4.3.1 [3+3] Cycloaddition Reactions 132</p> <p>4.4.3.2 [4+2] Cycloaddition Reactions 132</p> <p>4.4.3.3 [2+2+2] Cycloaddition Reactions 133</p> <p>4.4.3.4 Tandem Cycloaddition Reactions 133</p> <p>4.4.4 Biaryl Phenol Syntheses 133</p> <p>4.4.5 Miscellaneous Syntheses 134</p> <p>References 135</p> <p><b>5 4-(Hetero)Arylpiperidines 155</b></p> <p>5.1 Introduction 155</p> <p>5.2 Marketed 4-(Hetero)Arylpiperidine Drugs 155</p> <p>5.3 Medicinal Chemistry Case Studies 159</p> <p>5.3.1 Cardiovascular Applications 159</p> <p>5.3.2 Central Nervous System Applications 159</p> <p>5.3.3 Infectious Diseases Applications 168</p> <p>5.3.4 Inflammation Applications 169</p> <p>5.3.5 Men’s and Women’s Health Applications 174</p> <p>5.3.6 Metabolic Diseases Applications 175</p> <p>5.3.7 Oncology Applications 177</p> <p>5.4 Synthesis of 4-(Hetero)Arylpiperidines 179</p> <p>5.4.1 Preparation from 4-Piperidinones 179</p> <p>5.4.2 Preparation from 4-Prefunctionalized-3-alkenylpiperidines 180</p> <p>5.4.3 Preparation from Negishi Cross-Coupling of 3-Zincated Piperidines 180</p> <p>5.4.4 Preparation from 4-Funtionalized Piperidines 181</p> <p>5.4.5 Conjugated Addition to Unsaturated Piperidines 181</p> <p>5.4.6 Miscellaneous Syntheses 183</p> <p>References 185</p> <p><b>6 Spiropiperidines 194</b></p> <p>6.1 Introduction 194</p> <p>6.2 Marketed Spiropiperidine Drugs 194</p> <p>6.3 Medicinal Chemistry Case Studies 195</p> <p>6.3.1 Cardiovascular Applications 195</p> <p>6.3.2 Central Nervous System Applications 197</p> <p>6.3.3 Infectious Diseases Applications 203</p> <p>6.3.4 Inflammation Applications 205</p> <p>6.3.5 Men’s and Women’s Health Applications 210</p> <p>6.3.6 Metabolic Diseases Applications 211</p> <p>6.3.7 Oncology Applications 216</p> <p>6.4 Synthesis of Spiropiperidines 218</p> <p>6.4.1 Quinolinylspiropiperidines 218</p> <p>0003364809.INDD 7 12/18/2017 9:40:53 PM</p> <p>viii Contents</p> <p>6.4.2 Azaspiro[5.5]alkane Systems 218</p> <p>6.4.3 Diazaspiro[5.5]alkane Derivatives 221</p> <p>6.4.4 1,4-Benzodioxinylspiropiperidines 222</p> <p>6.4.5 Spirobenzooxazinylspiropiperidines 223</p> <p>6.4.6 (Iso)Quinolinylspiropiperidines 223</p> <p>6.4.7 Indenospiropiperidines 225</p> <p>6.4.8 Indolin(on)ylspiropiperidines 225</p> <p>6.4.9 Cyclohexadienonylspiropiperidines 226</p> <p>6.4.10 Cyclopenta[b]pyrrolospiropiperidines 226</p> <p>6.4.11 Chromanylspiropiperidines 226</p> <p>6.4.12 (Iso)Benzofuran(on)ylspiropiperidines 227</p> <p>6.4.13 Indenospiropiperidines 227</p> <p>References 228</p> <p><b>7 2-Aminopyrimidines 237</b></p> <p>7.1 Introduction 237</p> <p>7.2 Marketed 2-Aminopyrimidine Drugs 237</p> <p>7.3 Medicinal Chemistry Case Studies 239</p> <p>7.3.1 Cardiovascular Applications 239</p> <p>7.3.2 Central Nervous System Applications 241</p> <p>7.3.3 Infectious Diseases Applications 245</p> <p>7.3.4 Inflammation Applications 248</p> <p>7.3.5 Metabolic Diseases Applications 254</p> <p>7.3.6 Miscellaneous Applications 255</p> <p>7.3.7 Oncology Applications 256</p> <p>7.4 Synthesis of 2-Aminopyrimidines 267</p> <p>7.4.1 Aminations with 2-Halo or 2,4-Dihalopyrimidines 267</p> <p>7.4.2 Cross-Coupling Reactions with 2-Aminopyrimidines 270</p> <p>7.4.3 Aminations with 2-Sulfonylpyrimidines 270</p> <p>7.4.4 Cyclizations with Guanidines 272</p> <p>References 272</p> <p><b>8 2-Aminothiazoles 284</b></p> <p>8.1 Introduction 284</p> <p>8.2 Marketed 2-Aminothiazole Drugs 284</p> <p>8.3 Medicinal Chemistry Case Studies 286</p> <p>8.3.1 Cardiovascular Diseases Applications 286</p> <p>8.3.2 Central Nervous System Applications 288</p> <p>8.3.3 Infectious Diseases Applications 292</p> <p>8.3.4 Inflammation Applications 296</p> <p>8.3.5 Metabolic Diseases Applications 299</p> <p>8.3.6 Oncology Applications 301</p> <p>8.3.7 Miscellaneous Applications 305</p> <p>8.4 Synthesis of 2-Aminothiazoles 306</p> <p>8.4.1 Hantzsch Synthesis from α-Functionalized Ketones and Thioureas 306</p> <p>8.4.2 Hantzsch Synthesis from Ketones and Thioureas 306</p> <p>8.4.3 Synthesis from α-Haloketones and Thiocyanates 308</p> <p>8.4.4 Synthesis from Vinyl Azides and Thiocyanates 308</p> <p>8.4.5 Synthesis from Amidines and Thiocyanates 309</p> <p>8.4.6 Synthesis from Alkenyl and Alkynyl Compounds with Thiocyanates or Thioureas 309</p> <p>8.4.7 Miscellaneous Syntheses 309</p> <p>8.4.8 Elaboration of 2-Aminothiazoles 311</p> <p>References 311</p> <p><b>9 2-(Hetero)Arylindoles 321</b></p> <p>9.1 Introduction 321</p> <p>9.2 Marketed 2-Arylindole Drugs 321</p> <p>9.3 Medicinal Chemistry Case Studies 321</p> <p>9.3.1 Cardiovascular Applications 321</p> <p>9.3.2 Central Nervous System Applications 322</p> <p>9.3.3 Infectious Diseases Applications 323</p> <p>9.3.4 Inflammation Applications 325</p> <p>9.3.5 Men’s and Women’s Health Applications 326</p> <p>9.3.6 Metabolic Diseases Applications 328</p> <p>9.3.7 Miscellaneous Applications 328</p> <p>9.3.8 Oncology Applications 328</p> <p>9.4 Synthesis of 2-(Hetero)Arylindoles 332</p> <p>9.4.1 Functionalization to the Preformed Indole System 332</p> <p>9.4.1.1 2-Functionalized Metallated Indoles with Aryl Halides (Strategy 1) 332</p> <p>9.4.1.2 2-Halogenated or 2-Triflated Indoles with Functionalized Arenes (Strategy 1) 332</p> <p>9.4.1.3 Direct Arylation of Indole with Functionalized Arenes (Strategy 2) 334</p> <p>9.4.1.4 Direct Oxidative Coupling of Indoles with (Hetero)Arenes (Strategy 3) 334</p> <p>9.4.2 Fischer Indole Synthesis 334</p> <p>9.4.3 Bischler–Mohlau Indole Synthesis 334</p> <p>9.4.4 Metal-Catalyzed Approach with Alkynes 334</p> <p>9.4.4.1 Intramolecular Cyclizations of o-Alkynylanilines (Strategy A) 336</p> <p>9.4.4.2 Intramolecular Cyclizations of o-Alkynylanilines with Other Groups (Strategy B) 336</p> <p>9.4.4.3 Intramolecular Cyclizations of o-Haloanilines with Alkynes (Strategy C) 337</p> <p>9.4.4.4 Intramolecular Cyclizations of o-Alkynylhaloarenes with Primary Amines (Strategy D) 340</p> <p>9.4.4.5 Miscellaneous Transition Metal-Catalyzed Reactions 340</p> <p>9.4.4.6 Reductive Cyclizations of o-Nitroalkynylarenes 342</p> <p>9.4.5 Intracmolecular Reductive Cyclizations of o-Nitro (or Azido)alkenylarenes 342</p> <p>9.4.6 Cyclizations of Arylamido and Arylimine Precursors 343</p> <p>9.4.7 Cyclizations of o-Vinylaminoarenes 344</p> <p>9.4.8 Cyclizations with N-Arylenamines or N-Arylenaminones 344</p> <p>9.4.9 Multicomponent Synthesis 345</p> <p>9.4.10 Radical Cyclization Reactions 346</p> <p>9.4.11 Miscellaneous Cyclizations with o-Substituted Anilines 346</p> <p>References 348</p> <p><b>10 Tetrahydroisoquinolines 356</b></p> <p>10.1 Introduction 356</p> <p>10.2 Marketed THIQ Drugs 356</p> <p>10.3 Medicinal Chemistry Case Studies 357</p> <p>10.3.1 Cardiovascular Applications 357</p> <p>10.3.2 Central Nervous System Applications 359</p> <p>10.3.3 Infectious Diseases Applications 365</p> <p>10.3.4 Inflammation Applications 366</p> <p>10.3.5 Men’s and Women’s Health Applications 369</p> <p>10.3.6 Metabolic Diseases Applications 369</p> <p>10.3.7 Miscellaneous Applications 370</p> <p>10.3.8 Oncology Applications 372</p> <p>10.4 Synthesis of THIQs 376</p> <p>10.4.1 Pictet–Spengler Reactions 376</p> <p>10.4.1.1 Classical Pictet–Spengler Reactions 376</p> <p>10.4.1.2 Pictet–Spengler Reactions with Masked Carbonyl Compounds 377</p> <p>10.4.1.3 Modified Pictet–Spengler Reactions 377</p> <p>10.4.1.4 Pictet–Spengler-Type Reactions 377</p> <p>10.4.1.5 Pictet–Spengler Synthesis of Tic 378</p> <p>10.4.2 Transition Metal-Catalyzed Reactions 379</p> <p>10.4.2.1 Intramolecular α-Arylation Reactions 379</p> <p>10.4.2.2 Intramolecular Cyclizations of N-Propargylbenzylamines 379</p> <p>10.4.2.3 Intramolecular Heck Cyclizations 379</p> <p>10.4.2.4 Intramolecular Nucleophilic Additions 379</p> <p>10.4.2.5 One-Pot Multistep Metal-Catalyzed Cyclization Reactions 380</p> <p>10.4.3 Multicomponent Synthesis of THIQs 382</p> <p>10.4.4 Synthesis of 3-Aryltetrahydroisoquinolines 382</p> <p>10.4.5 Synthesis of 4-Aryltetrahydroisoquinolines 383</p> <p>10.4.6 Miscellaneous Intramolecular Cyclizations 386</p> <p>10.4.7 Asymmetric Reduction of 1-Substituted-3,4-</p> <p>Dihydroisoquinolines 387</p> <p>10.4.7.1 Iridium-Catalyzed Hydrogenations of Dihydroisoquinolines, Isoquinoline Salts, and Isoquinolines 388</p> <p>10.4.7.2 Ruthenium- and Rhodium-Catalyzed Reductions of Dihydroisoquinolines 389</p> <p>10.4.7.3 Asymmetric Additions to Dihydroisoquinolines, Dihydroisoquinoline</p> <p>Salts, and Dihydroisoquinoline N-Oxides 389</p> <p>10.4.7.4 Asymmetric Intramolecular Cyclizations 391</p> <p>10.4.7.5 Asymmetric Intramolecular Cyclizations with Chiral Sulfoxides 391</p> <p>10.4.7.6 Miscellaneous Asymmetric Preparations 392</p> <p>10.4.8 Arylations of THIQs 393</p> <p>10.4.9 C„ŸH Functionalization of THIQs 395</p> <p>10.4.9.1 Direct C-1 (Hetero)Arylations of THIQs 395</p> <p>10.4.9.2 Oxidative C-1 CDC Reactions 395</p> <p>10.4.9.3 Oxidative C-1 CDC with β-Ketoesters 396</p> <p>10.4.9.4 Oxidative C-1 CDC with Ketones 397</p> <p>10.4.9.5 Oxidative C-1 CDC with Indoles 397</p> <p>10.4.9.6 Oxidative C-1 CDC with Aliphatic Nitro Compounds 398</p> <p>10.4.9.7 Oxidative C-1 CDC with Alkynes 399</p> <p>10.4.9.8 Oxidative C-1 CDC with Alkenes 399</p> <p>10.4.9.9 Oxidative C-1 Cross-Dehydrogenative Phosphonations 400</p> <p>10.4.9.10 Miscellaneous Oxidative C-1 CDC Reactions 400</p> <p>References 401</p> <p><b>11 2,2-Dimethylbenzopyrans 414</b></p> <p>11.1 Introduction 414</p> <p>11.2 Marketed 2,2-Dimethylopyran Drugs 414</p> <p>11.3 Medicinal Chemistry Case Studies 415</p> <p>11.3.1 Cardiovascular Applications 415</p> <p>11.3.2 Central Nervous System Applications 416</p> <p>11.3.3 Infectious Diseases Applications 418</p> <p>11.3.4 Inflammation Applications 419</p> <p>11.3.5 Metabolic Diseases Applications 419</p> <p>11.3.6 Oncology Applications 419</p> <p>11.3.7 Cannabinoid Receptors 421</p> <p>11.4 Synthesis of 2,2-Dimethylbenzopyrans 423</p> <p>11.4.1 Annulations of Phenol Derivatives with Unsaturated Systems 423</p> <p>11.4.1.1 Annulations of Phenol Derivatives with Simple Alkenes 423</p> <p>11.4.1.2 Annulations of Phenol Derivatives with α,β-Unsaturated Systems 424</p> <p>11.4.1.3 Annulations of Phenol Derivatives with Nitroalkenes 424</p> <p>11.4.1.4 Annulations of Phenol Derivatives with Allylic Alcohols 424</p> <p>11.4.1.5 Annulations of Phenol Derivatives with Propargyl Alcohols 425</p> <p>11.4.2 Replacement of the Methyl Group of 2,2-Dimethylbenzopyrans 425</p> <p>11.4.3 Functionalization of 2,2,-Dimethylbenzopyrans 426</p> <p>11.4.4 Fused 2,2-Dimethylbenzopyran Ring Systems 428</p> <p>11.4.5 Solid-Phase Synthesis of 2,2-Dimethylbenzopyrans 428</p> <p>References 429</p> <p><b>12 Hydroxamates 435</b></p> <p>12.1 Introduction 435</p> <p>12.2 Marketed Hydroxame Drugs 435</p> <p>12.3 Medicinal Chemistry Case Studies 436</p> <p>12.3.1 Central Nervous System Applications 436</p> <p>12.3.2 Infectious Diseases Applications 436</p> <p>12.3.3 Inflammation Applications 439</p> <p>12.3.4 Men’s and Women’s Health Applications 452</p> <p>12.3.5 Metabolic Diseases Applications 453</p> <p>12.3.6 Oncology Applications 453</p> <p>12.4 Synthesis of Hydroxamates 466</p> <p>12.4.1 Synthesis of Hydroxamates from Carboxylic Acids 466</p> <p>12.4.2 Synthesis of Hydroxamates from Carboxylic Acid Derivatives 466</p> <p>12.4.2.1 Synthesis of Hydroxamates from Esters 466</p> <p>12.4.2.2 Synthesis of Hydroxamates from Acid Chlorides 468</p> <p>12.4.2.3 Synthesis of Hydroxamates from Oxazolidinones 468</p> <p>12.4.3 Miscellaneous Syntheses of Hydroxamates 469</p> <p>12.4.4 Solid-Phase Synthesis of Hydroxamates 469</p> <p>References 470</p> <p><b>13 Bicyclic Pyridines Containing Ring-Junction Nitrogen 481</b></p> <p>13.1 Introduction 481</p> <p>13.2 Marketed Bicyclic Ring-Junction Pyridine Drugs 481</p> <p>13.3 Medicinal Chemistry Case Studies 482</p> <p>13.3.1 Cardiovascular Applications 482</p> <p>13.3.2 Central Nervous System Applications 483</p> <p>13.3.3 Gastrointestinal Applications 487</p> <p>13.3.4 Infectious Diseases Applications 488</p> <p>13.3.5 Inflammation Applications 491</p> <p>13.3.6 Metabolic Diseases Applications 493</p> <p>13.3.7 Miscellaneous Applications 494</p> <p>13.3.8 Oncology Applications 494</p> <p>13.4 Synthesis of Pyrazolo[1,5-a]pyridines 498</p> <p>13.4.1 [3+2] Dipolar Cycloadditions 498</p> <p>13.4.2 Intramolecular Cyclizations 499</p> <p>13.4.3 From N-Aminopyridinium Ylides 500</p> <p>13.4.4 From 2-Substituted Pyridines 500</p> <p>13.4.5 Thermal and Radical Cyclizations 500</p> <p>13.5 Synthesis of Imidazo[1,5-a]pyridines 501</p> <p>13.5.1 From 2-Methylaminopyridines 501</p> <p>13.5.2 From 2-Methylaminopyridine Amides 502</p> <p>13.5.3 From 2-Methylaminopyridine Thioamides or Thioureas 503</p> <p>13.5.4 From Pyridine-2-Carbaldehydes (Picolinaldehydes) 503</p> <p>13.5.5 From 2-Cyanopyridines 503</p> <p>13.5.6 From Pyridine-2-Esters 504</p> <p>13.5.7 From Di-2-Pyridyl Ketones 504</p> <p>13.5.8 From Pyridotriazoles 504</p> <p>13.5.9 Miscellaneous Syntheses 504</p> <p>13.5.10 Chemical Elaborations of Imidazo[1,5-a]pyridines 505</p> <p>13.6 Synthesis of Imidazo[1,2-a]pyridines 507</p> <p>13.6.1 Ugi Three-Component Reactions 507</p> <p>13.6.1.1 Classical Ugi Three-Component Reactions of 2-Aminopyridines, Aldehydes, and (Iso)Nitriles 507</p> <p>13.6.1.2 Modified Ugi Three-Component Reactions 507</p> <p>13.6.2 From 2-Aminopyridines and Carbonyl Compounds 509</p> <p>13.6.2.1 From 2-Aminopyridines and Methyl Ketones 509</p> <p>13.6.2.2 From 2-Aminopyridines and β-Ketoesters 509</p> <p>13.6.2.3 From 2-Aminopyridines and Miscellaneous Ketones 510</p> <p>13.6.2.4 From Pyridines and 2-Aminopyridines with α-Haloketones or α-Haloaldehydes 511</p> <p>13.6.3 From 2-Aminopyridines and Alkynes 512</p> <p>13.6.3.1 From 2-Aminopyridines and Alkynes 512</p> <p>13.6.3.2 From 2-Aminopyridines, Alkynes, and Aldehydes 513</p> <p>13.6.4 From 2-Aminopyridines and α,β-Unsaturated Systems 513</p> <p>13.6.5 From 2-Aminopyridines and Nitroolefins 515</p> <p>13.6.6 Cyclizations from 2-Aminopropargylpyridines 515</p> <p>13.6.7 Cyclizations from Pyridyl Enamines(ones) 517</p> <p>13.6.8 From Other Heterocycles 517</p> <p>13.6.9 Miscellaneous Syntheses 518</p> <p>13.6.10 Chemical Elaboration of Imidazo[1,2-a]pyridines 520</p> <p>13.6.10.1 Cross-Coupling Reactions of Pre-functionalized Imidazo[1,2-a]pyridines 520</p> <p>13.6.10.2 C„ŸH Functionalization of Imidazo[1,2-a]pyridines 521</p> <p>13.6.11 Fused Imidazo[1,2-a]pyridine Ring Systems 523</p> <p>References 525</p> <p>Index</p>
<p> <strong>Larry Yet, PhD,</strong> is an Assistant Professor in the Department of Chemistry at the University of South Alabama. He has authored or coauthored more than 40 publications, is an inventor on several non-provisional and issued patents, and has written multiple invited book chapters and review articles in synthetic organic and medicinal chemistry.
<p> <strong>A comprehensive guide to privileged structures and their application in the discovery of new drugs </strong> <p> The use of privileged structures is a viable strategy in the discovery of new medicines at the lead optimization stages of the drug discovery process. <em>Privileged Structures in Drug Discovery</em> offers a comprehensive text that reviews privileged structures from the point of view of medicinal chemistry and contains the synthetic routes to these structures. In this text, the author—a noted expert in the field—includes an historical perspective on the topic, presents a practical compendium to privileged structures, and offers an informed perspective on the future direction for the field. <p> The book describes the up-to-date and state-of-the-art methods of organic synthesis that describe the use of privileged structures that are of most interest. Chapters included information on benzodiazepines, 1,4-dihydropyridines, biaryls, (hetero)arylpiperidines, spiropiperidines, 2-aminopyrimidines, 2-aminothiazoles, 2-(hetero)arylindoles, tetrahydroisoquinolines, 2,2-dimethylbenzopyrans, hydroxamates, and bicyclic pyridines containing ring-junction nitrogen as privileged scaffolds in medicinal chemistry. Numerous, illustrative case studies document the current use of the privileged structures in the discovery of drugs. This important volume: <ul> <li>Describes the drug compounds that have successfully made it to the marketplace and the chemistry associated with them</li> <li>Offers the experience from an author who has worked in many therapeutic areas of medicinal chemistry</li> <li>Details many of the recent developments in organic chemistry that prepare target molecules</li> <li>Includes a wealth of medicinal chemistry case studies that clearly illustrate the use of privileged structures</li> </ul> <br> <p> Designed for use by industrial medicinal chemists and process chemists, academic organic and medicinal chemists, as well as chemistry students and faculty, <em>Privileged Structures in Drug Discovery</em> offers a current guide to organic synthesis methods to access the privileged structures of interest, and contains medicinal chemistry case studies that document their application.

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