Advances in Antiviral Drug Design (eBook)

Cover 1
Contents 6
List of Contributors 8
Preface 10
Chapter 1. Status Presens of Antiviral Drugs And Strategies: Part I: DNA Viruses and Retroviruses 14
Abstract 14
I. Introduction 14
II. Parvoviruses 15
III. Polyomaviruses 15
IV. Papillomaviruses 16
V. Adenoviruses 17
VI. alpha-Herpesviruses (HSV-1, HSV-2, VZV) 17
VII. beta-Herpesviruses (CMV, HHV-6, HHV-7) 19
VIII. gamma-Herpesviruses (EBV, HHV-8) 21
IX. Poxviruses (variola, vaccinia, monkeypox, molluscum contagiosum, orf ƒ) 22
X. Hepadnaviruses (HBV) 24
XI. Retroviruses (HIV) 27
XII. Conclusion 53
Acknowledgements 59
References 59
Chapter 2. Status presens of antiviral drugs and strategies: Part II: RNA VIRUSES (EXCEPT RETROVIRUSES) 72
Abstract 72
I. Introduction 72
II. Picornaviruses (entero- and rhinoviruses) 73
III. Alpha- and flaviviruses (yellow fever, dengue, west nile, ƒ) 75
IV. Hepaciviruses (HCV) 76
V. Coronaviruses (SARS) 83
VI. Orthomyxoviruses (influenza A, B) 86
VII. Paramyxoviruses (parainfluenza, measles, mumps, RSV, hMPV, Nipah, ƒ) 88
VIII. Arena-, bunya-, rhabdo- and filoviruses 96
IX. Reoviruses 109
X. Conclusion 110
References 110
Chapter 3. Methylenecyclopropane Analogues of Nucleosides as Anti-herpes Agents 126
Abstract 126
I. Introduction 126
II. Design 129
III. Synthesis 132
IV. Antiviral activity 147
Acknowledgements 172
References 173
Chapter 4. Synthesis and antiviral evaluation of broad spectrum, orally active analogs of cidofovir and other acyclic nucleoside phosphonates 180
I. Introduction 180
II. Synthesis of hexadecyloxypropyl and related esters of cidofovir 181
III. Antiviral evaluation and spectrum of activity 184
IV. Structure activity relationships 186
V. Cellular metabolism 188
VI. Oral pharmacokinetics and tissue distribution 189
VII. Antiviral activity in animal models of viral diseases 191
VIII. Alkoxyalkyl esters of (S)-HPMPA and other acyclic nucleoside phosphonates 194
IX. Conclusions 195
Acknowledgements 195
References 196
Chapter 5. CCR5 antagonistsCCR5 antagonists for the treatment ofHIV infection and AIDS 198
I. Introduction 198
II. Inhibition of HIV entry 199
III. CCR5 as a drug target 201
IV. The discovery of novel CCR5 antagonists 203
V. Molecular mechanisms 212
VI. Resistance to CCR5 antagonists in vitro and in the clinic 214
VII. Conclusions 215
References 217
Chapter 6. The medicinal chemistry of the DATADATA and DAPYDAPY series of HIV-1HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIsNNRTIs) 226
Abstract 226
I. Introduction 227
II. The diaryltriazine (DATA) series 229
III. The diarylpyrimidine (DAPY) series 235
IV. Conclusion 252
Acknowledgements 252
References 252
Index 256