Antiviral drug strategies

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Weitere Verfasser: DeClercq, Erik (HerausgeberIn)
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Veröffentlicht: Weinheim Wiley-VCH-Verl. 2011
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adam_text IMAGE 1 CONTENTS LIST OF CONTRIBUTORS XIII PREFACE XVII A PERSONAL FOREWORD XIX 1 OUTLOOK OF THE ANTIVIRAL DRUG ERA, NOW MORE THAN 50 YEARS AFTER DESCRIPTION OF THE FIRST ANTIVIRAL DRUG 1 ERIK DE CLERCQ 1.1 INTRODUCTION: THE PREHISTORY 1 1.2 KEY EVENTS IN ANTIVIRAL DRUG DEVELOPMENT 2 1.3 ANTIVIRAL DRUGS: CURRENT STATE OF THE ART 4 1.4 ANTIVIRAL DRUGS ACTIVE AGAINST HERPESVIRUSES (I.E., HSV, VZV, AND SO ON) 4 1.5 ANTIVIRAL DRUGS ACTIVE AGAINST RETROVIRUSES (HIV) 8 1.6 ANTIVIRAL DRUGS ACTIVE AGAINST HEPATITIS B VIRUS 12 1.7 ANTIVIRAL DRUGS ACTIVE AGAINST DNA VIRUSES AT LARGE 13 1.8 ANTIVIRAL DRUGS FOR INFLUENZA A VIRUS INFECTIONS 14 1.9 ANTIVIRAL DRUGS FOR HEPATITIS C VIRUS 25 1.10 ANTIVIRAL DRUGS FOR POXVIRUSES (I.E., VARIOLA, VACCINIA, AND SO ON) 17 1.11 FURTHER OPTIONS TO TREAT VIRUS INFECTIONS 19 1.12 CONCLUSIONS 19 REFERENCES 20 2 INHIBITION OF HIV ENTRY 29 JOSE A. ESTE 2.1 INTRODUCTION 29 2.2 THE HIV GLYCOPROTEINS 30 2.2.1 STRUCTURE OF THE HIV-1 GLYCOPROTEIN GPL20 30 2.2.2 STRUCTURE OF THE HIV-1 TRANSMEMBRANE GLYCOPROTEIN GP41 31 2.3 MECHANISM OF HIV ENTRY 32 2.3.1 VIRUS ATTACHMENT 32 2.3.2 CORECEPTORS: VIRUS TROPISM AND INFECTIVITY 33 BIBLIOGRAFISCHE INFORMATIONEN HTTP://D-NB.INFO/1007936916 DIGITALISIERT DURCH IMAGE 2 VI CONTENTS 2.3.3 2.3.4 2.4 2.4.1 2.4.1.1 2.4.1.2 2.4.2 2.4.3 2.4.3.1 2.4.3.2 2.4.3.3 2.4.3.4 2.4.4 2.4.5 2.5 VIRUS-CELL FUSION 33 ENDOCYTOSIS OF HIV 33 INHIBITION OF HIV ENTRY 34 INHIBITORS OF VIRUS ATTACHMENT 34 POLYANIONS AS INHIBITORS OF HIV ATTACHMENT 34 SMALL-MOLECULE INHIBITORS OF THE GPL20-CD4 INTERACTION 36 POSTATTACHMENT INHIBITORS 37 CCR5 ANTAGONISTS 38 MARAVIROC 38 VICRIVIROC 39 PRO-140 39 RESISTANCE TO CCR5 ANTAGONISTS 39 CXCR4 ANTAGONISTS 40 INHIBITORS OF HIV FUSION: ENFUVIRTIDE 41 CONCLUDING REMARKS 42 REFERENCES 42 3 TARGETING INTEGRATION BEYOND STRAND TRANSFER: DEVELOPMENT OF SECOND-GENERATION HIV INTEGRASE INHIBITORS 51 ARNOUT R.D. VOET, MARC DE MAEYER, FRAUKE CHRIST, AND ZEGER DEBYSER 3.1 HIV: THE CAUSATIVE AGENT OF AIDS 51 3.1.1 REPLICATION CYCLE OF HIV 51 3.1.2 HIGHLY ACTIVE ANTIRETROVIRAL THERAPY 52 3.2 THE INTEGRATION STEP: A COMPLEX MECHANISM WITH DIFFERENT POSSIBILITIES FOR INHIBITION 53 3.2.1 HIV-1 INTEGRASE 53 3.2.1.1 THE STRUCTURAL ORGANIZATION OF HIV-1 INTEGRASE 54 3.2.2 HIV-1 IN AS A TARGET FOR HAART 55 3.2.2.1 INTEGRASE STRAND TRANSFER INHIBITORS 55 3.2.2.2 INTEGRASE BINDING INHIBITORS 57 3.3 DNA BINDING INHIBITORS 59 3.4 MULTIMERIZATION INHIBITORS 60 3.5 TARGETING INTEGRASE COFACTOR INTERACTIONS 62 3.6 CONCLUSION 64 REFERENCES 65 4 FROM SAQUINAVIR TO DARUNAVIR: THE IMPACT OF 10 YEARS OF MEDICINAL CHEMISTRY ON A LETHAL DISEASE 73 MARIE-PIERRE DE BETHUNE, ANIK PEETERS, AND PIET WIGERINCK 4.1 INTRODUCTION 73 4.2 THE HIV PROTEASE AS A TARGET FOR AIDS 73 4.3 THE EARLY PROTEASE INHIBITORS 74 4.4 THE MEDICAL NEED FOR A NEXT -GENERATION PI 78 4.5 HOW CAN WE EXPLAIN THE SUPERIOR ANTIVIRAL ACTIVITY OF DARUNAVIR? 85 IMAGE 3 CONTENTS VII 4.6 CLINICAL DEVELOPMENT OF DARUNAVIR 86 4.7 CONCLUSIONS AND FUTURE DEVELOPMENTS 87 REFERENCES 87 5 ACYCLIC AND CYCLIC NUCLEOSIDE PHOSPHONATES 91 RICHARD L MACKMAN AND TOMAS CIHLAR 91 5.1 INTRODUCTION 91 5.2 NUCLEOSIDE PHOSPHONATE STRATEGY FOR ANTIVIRALS 92 5.3 ACYCLIC NUCLEOSIDE PHOSPHONATES 95 5.3.1 MAIN CLASSES AND THEIR STRUCTURE-ACTIVITY RELATIONSHIPS 95 5.3.1.1 HPMP ANALOGUES 95 5.3.1.2 PME ANALOGUES 95 5.3.1.3 PMP AND FPMP ANALOGUES 97 5.3.2 ADDITIONAL EXAMPLES OF ANTIVIRAL ANPS 98 5.4 CYCLIC NUCLEOSIDE PHOSPHONATES 99 5.4.1 MAIN CLASSES AND THEIR STRUCTURE-ACTIVITY RELATIONSHIPS 100 5.4.1.1 TETRAHYDROFURAN CORE 100 5.4.1.2 CYDOPENTANE AND CYCLOPENTENE CORES 103 5.4.2 EXAMPLES OF CNPS TARGETING VIRAL RNA POLYMERASES 104 5.5 PRODRUGS OF NUCLEOSIDE PHOSPHONATES 107 5.5.1 PHOSPHONOESTERS 107 5.5.2 PHOSPHONOAMIDATES 109 5.6 CLINICAL APPLICATIONS OF ANTIVIRAL NUCLEOSIDE PHOSPHONATES 111 5.6.1 CIDOFOVIR (VISTIDE) 112 5.6.2 ADEFOVIR DIPIVOXIL (HEPSERA) 112 5.6.3 TENOFOVIR DISOPROXIL FUMARATE (VIREAD) 113 5.7 CONCLUSIONS 115 REFERENCES 115 6 HELICASE-PRIMASE INHIBITORS: A NEW APPROACH TO COMBAT HERPES SIMPLEX VIRUS AND VARICELLA ZOSTER VIRUS 129 SUBHAJIT BISWAS AND HUGHJ. FIELD 6.1 INTRODUCTION 129 6.2 THE ROLE OF HELICASE PRIMASE IN THE REPLICATION OF HSV 130 6.3 SELECTIVE INHIBITORS OF HELICASE PRIMASE AS ANTIHERPESVIRUS ANTIVIRALS 131 6.4 HPIS ARE EFFECTIVE IN CELL CULTURE AND IN VIVO 133 6.5 EFFECTS OF HPIS ON THE ESTABLISHMENT AND REACTIVATION FROM LATENCY 134 6.6 HPIS: THE BIOCHEMICAL BASIS FOR THE PROPOSED MECHANISM OFACTION 134 6.7 HSV ACQUIRED RESISTANCE TO HPIS 135 6.8 PATTERNS OF CROSS-RESISTANCE 136 6.9 FURTHER INSIGHT INTO MODE OF HPI INTERACTION WITH THE HSV HP COMPLEX FROM THE STUDY OF RESISTANCE MUTATIONS 139 IMAGE 4 VIII CONTENTS 6.10 THE FREQUENCY AND ORIGIN OF HPI-RESISTANCE MUTATIONS 140 6.11 UL5 LYS356ASN: A MUTATION CONFERRING HIGH RESISTANCE TO HPI 141 6.12 THE ORIGIN OF RESISTANCE MUTATIONS AT HIGH FREQUENCY 142 6.13 CONCLUSIONS 142 REFERENCES 144 7 CYCLOPHILIN INHIBITORS 147 CREGOIRE VUAGNIAUX, ARNAUD HAMEL, RAFAEL CRABBE, HERVI C. PORCHET, AND JEAN-MAURICE DUMONT 7.1 INTRODUCTION 147 7.2 CYCLOPHILIN OVERVIEW 148 7.3 CYCLOPHILIN INHIBITORS CURRENTLY IN CLINICAL DEVELOPMENT 148 7.3.1 CHEMICAL STRUCTURE 149 7.3.2 CYPA PPIASE INHIBITION AND LACK OF IMMUNOSUPPRESSIVE ACTIVITY 149 7.4 CYCLOPHILIN AND HIV 149 7 .4.1 CYCLOPHILIN INHIBITORS AGAINST HIV-1 151 7.4.1.1 IN VITRO ANTI-HIV-1 ACTIVITY 151 7.4.1.2 RESISTANCE PROFILE 152 7.4.1.3 IN VIVO ACTIVITY 152 7.4.1.4 PUTATIVE MECHANISM OF ACTION OF CYCLOPHILIN INHIBITORS AGAINST HIV-1 152 7.4.1.5 CLINICAL ACTIVITY OF DEBIO 025 AGAINST HIV-1 153 7.4.2 NO ACTIVITY AGAINST SIMIAN IMMUNODEFICIENCY VIRUS 154 7.4.3 ACTIVITY AGAINST HIV-2 154 7.5 CYCLOPHILIN AND HEPATITIS C 155 7.5.1 PUTATIVE ROLE OF CYCLOPHILIN IN HCV REPLICATION 155 7.5.2 ACTIVITY OF CYCLOPHILIN INHIBITORS IN HCV 157 7.5.3 RESISTANCE PROFILE 158 7.6 CLINICAL RESULTS IN HCV 159 7.6.1 DEBIO 025 159 7.6.1.1 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY IN HIV-1/HCV COINFECTED OR HIV-1 MONOINFECTED PATIENTS 159 7.6.1.2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, ESCALATING DOSE RANGING STUDY OF DEBIO 025 IN COMBINATION WITH PEGASYS IN TREATMENT-NAIVE PATIENTS WITH CHRONIC HEPATITIS 259 7.6.2 STUDY OF DEBIO 025 IN COMBINATION WITH PEG-IFN X2 AND RIBAVIRIN IN CHRONIC HCV GENOTYPE 1 NONRESPONDING PATIENTS 262 7.6.3 ADVERSE EVENTS 267 7.6.4 NIM811 AND SCY635 167 7.7 ACTIVITY AGAINST OTHER VIRUSES 167 7.8 NEW NONCYCLOSPORINE CYCLOPHILIN INHIBITORS 268 7.8.1 PEPTIDES AND PEPTIDOMIMETICS 268 7.8.2 CSA BIS-UREA DERIVATIVES 269 7.8.3 DIMEDONE-IIKE MOLECULES 269 IMAGE 5 CONTENTS IX 7.8.4 QUINOXALINE DERIVATIVES 169 7.8.5 DIARYLUREA DERIVATIVES 270 7.8.6 OTHER ACYLUREA DERIVATIVES 272 7.9 CONCLUSION 173 REFERENCES 273 8 ALKOXYALKYL ESTER PRODRUGS OF ANTIVIRAL NUCLEOSIDE PHOSPHATES AND PHOSPHONATES 282 JAMES R. BEADLE AND KARL Y. HOSTETLER 8.1 INTRODUCTION 281 8.2 ENHANCING THE ORAL ACTIVITY OF ANTIVIRAL COMPOUNDS: OVERVIEW OF THE DEVELOPMENT OF ALKOXYALKYL ESTERIFICATION APPROACH 282 8.3 ALKYLGLYCEROL AND ALKOXYALKYL PRODRUGS OF PHOSPHONOFORMATE: ENHANCED ANTIVIRAL ACTIVITY AND SYNERGISM WITH AZT 285 8.4 ALKOXYALKYL ESTERS OF NUCLEOSIDE 5 -MONOPHOSPHATES 285 8.5 ORAL PRODRUGS OF ACYCLIC NUCLEOSIDE PHOSPHONATES 189 8.5.1 CIDOFOVIR 189 8.5.1.1 ACTIVITY AGAINST POXVIRUSES IN VITRO 189 8.5.1.2 ACTIVITY AGAINST OTHER DOUBLE-STRANDED DNA VIRUSES IN VITRO 190 8.5.1.3 EFFICACY OF ALKOXYALKYL ESTERS OF ANPS IN ANIMAL MODELS OF DISEASE 192 8.5.2 ALKOXYALKYL ESTERS OF (S)-HPMPA 292 8.5.3 ALKOXYALKYL ESTERS OF TENOFOVIR (HDP-(K)-PMPA) 196 8.5.4 HEXADECYLOXYPROPYL ADEFOVIR AND PRODRUGS OF OTHER ANPS AND ANTIVIRALS 197 8.6 INTRAOCULAR DELIVERY OF ANTIVIRAL PRODRUGS FOR TREATMENT OR PREVENTION OF CYTOMEGALOVIRUS RETINITIS 298 8.6.1 L-O-OCTADECYL-SN-GLYCERO-3-PHOSPHONOFORMATE (ODG-PFA) 198 8.6.2 HEXADECYLOXYPROPYL GANCICLOVIR 5 -MONOPHOSPHATE (HDP-P-GCV) 299 8.6.3 HEXADECYLOXYPROPYL ESTERS OF CYCLIC CIDOFOVIR AND CYCLIC (S)-HPMPA 200 8.7 CONCLUSION 202 REFERENCES 202 9 MARIBAVIR: A NOVEL BENZIMIDAZOLE RIBONUCLEOSIDE FOR THE PREVENTION AND TREATMENT OF CYTOMEGALOVIRUS DISEASES 209 KAREN K. BIRON 9.1 CYTOMEGALOVIRUS DISEASES: UNMET CHALLENGES 209 9.2 MARIBAVIR ANTIVIRAL ACTIVITY 210 9.3 MARIBAVIR MECHANISMS OF ACTION AND RESISTANCE 212 9.4 PREDINICAL STUDIES 214 9.5 CLINICAL DEVELOPMENT OF MARIBAVIR: EARLY PHASE I 225 9.6 CLINICAL DEVELOPMENT IN A TRANSPLANT POPULATION 228 IMAGE 6 X CONTENTS 9.7 SUMMARY AND CONDUSIONS REFERENCES 222 220 10 ANTI-HCMV COMPOUNDS 227 CRACIELA ANDREI AND ROBERT SNOECK 10.1 INTRODUCTION 227 10.2 ANTI-HCMV DRUGS IN CLINICAL USE 229 10.2.1 CLASSES OF ANTI-HCMV DRUGS 229 10.2.2 TOXIDTY ASSOCIATED WITH APPROVED ANTI-HCMV DRUGS 231 10.2.3 RESISTANCE TO ANTI-HCMV ANTIVIRALS 233 10.3 NEED FOR NEW ANTI-HCMV DRUGS 234 10.4 NOVEL VIRAL TARGETS 235 10.4.1 VIRAL ENTRY INHIBITORS 235 10.4.1.1 SS-PEPTIDES 235 10.4.1.2 DENDRIMERS 235 10.4.1.3 AMPHIPATHIC DNA POLYMERS 237 10.4.1.4 THIOUREA DERIVATIVES 237 10.4.1.5 PHOSPHOROTHIOATE-MODIFIED OLIGONUCLEOTIDES 237 10.4.2 INHIBITORS OF VIRAL GENOME REPLICATION 238 10.4.2.1 DNA POLYMERASE INHIBITORS 238 10.4.2.2 HELICASE/PRIMASE INHIBITORS 245 10.4.2.3 INHIBITORS OF PROTEIN-PROTEIN INTERACTIONS 246 10.4.3 VIRAL GENE EXPRESSION INHIBITORS 248 10.4.3.1 SMALL INTERFERING RNAS 248 10.4.4 INHIBITORS OF VIRION ASSEMBLY AND EGRESS 248 10.4.4.1 INHIBITORS OF DNA CLEAVAGE/PACKAGING 248 10.4.4.2 UL97 PROTEIN KINASE (PUL97) INHIBITORS 252 10.4.4.3 VIRAL PROTEASE INHIBITORS 256 10.4.5 ADDITIONAL NEW INHIBITORS OF HCMV 256 10.4.5.1 AGONIST FOR HCMV-ENCODED CHEMOKINE RECEPTORS 256 10.4.6 HCMV INHIBITORS WITH A MECHANISM OF ACTION NOT FULLY UNRAVELED 258 10.4.6.1 CMV423 258 10.4.6.2 BERBERINE CHLORIDE, ARYLSULFONE DERIVATIVES, IIPOPHILIC ALKYL FURANO PYRIMIDINE DIDEOXY NUDEOSIDES, AND 4 -BENZOYL-UREIDO-TSAO DERIVATIVES 258 10.4.6.3 LEFLUNOMIDE 259 10.4.6.4 ARTESUNATE 260 10.5 CELLULAR TARGETS 260 10.5.1 INHIBITORS OF CYDIN-DEPENDENT KINASES 261 10.5.2 INHIBITORS OF CYCLOOXYGENASE 2 262 10.5.3 PROTEASOME INHIBITORS 263 10.6 CONCLUSIONS 265 REFERENCES 266 IMAGE 7 CONTENTS XI 11 LETHAL MUTAGENESIS AS AN UNCONVENTIONAL APPROACH TO COMBAT HIV 283 PINAR LYIDOGAN AND KAREN S. ANDERSON 11.1 INTRODUCTION 283 11.2 VIRAL FITNESS AND INTRINSIC MUTAGENESIS IN RNA VIRUSES AND RETROVIRUSES 284 11.3 FUNDAMENTALS OF LETHAL MUTAGENESIS 286 11.4 MUTAGENIC PHARMACEUTICALS AS ANTIVIRAL AGENTS 288 11.4.1 RIBAVIRIN 288 11.4.2 5-OH-DC 290 11.4.3 5-AZC 292 11.5 KP-1212: FROM BENCH TO CLINIC 292 11.6 CHALLENGES AND ADVANTAGES OF LETHAL MUTAGENESIS COMPARED TO CONVENTIONAL STRATEGIES 294 11.7 CONDUDING REMARKS AND FUTURE PERSPECTIVES 296 REFERENCES 298 12 RECENT PROGRESS IN THE DEVELOPMENT OF HCV PROTEASE INHIBITORS 307 NAGRAJ MANI, BHISETTI C. RAO, TARA L KIEFFER, AND ANN D. KWONG 12.1 INTRODUCTION 307 12.2 HCV THERAPY 307 12.2.1 THE ROLE OF HCV PROTEASE 308 12.2.2 HCV PROTEASE INHIBITOR DESIGN 310 12.2.3 SIMILARITIES AND DIFFERENCES IN HCV PROTEASE INHIBITORS 310 12.2.4 ANTIVIRAL POTENCY AND THE EMERGENCE OF RESISTANCE 326 12.3 MECHANISM OF RESISTANCE AND CROSS-RESISTANCE TO NS3 PROTEASE INHIBITORS 316 12.3.1 PATTERN OF RESISTANCE TO COVALENT LINEAR PROTEASE INHIBITORS 316 12.3.2 PATTERN OF RESISTANCE TO NONCOVALENT PROTEASE INHIBITORS 318 12.3.3 CROSS-RESISTANCE BETWEEN LINEAR AND MACROCYCLIC HCV PROTEASE INHIBITORS 328 12.4 ANTIVIRAL POTENCY AND CLINICAL EFFICACY OF HCV PROTEASE INHIBITORS 319 12.4.1 TELAPREVIR 329 12.4.2 BOCEPREVIR 320 12.4.3 SAFETY PROFILE OF PROTEASE INHIBITORS 321 12.5 FUTURE DIRECTIONS 321 REFERENCES 322 13 ANTIVIRAL RNAI: HOW TO SILENCE VIRUSES 329 KARIN J. VON EIJE AND BEN BERKHOUT 13.1 THE DISCOVERY OF RNA INTERFERENCE 329 13.2 THERAPEUTIC APPLICATION OF THE RNAI MECHANISM 329 13.3 MAMMALIAN VIRUSES AND THE RNAI MECHANISM 331 IMAGE 8 XII CONTENTS 13.4 BASIC DESIGN OF AN RNAI THERAPY AGAINST VIRUSES 332 13.5 SELECTING OPTIMAL TARGETS 332 13.6 PREVENTION OF VIRAL ESCAPE 334 13.7 MULTIPLEXING SIRNAS 335 13.8 DELIVERY ISSUES 335 13.9 POTENTIAL RISKS OF AN RNAI THERAPY 336 13.10 EXAMPLE OF AN ACUTE INFECTION: RSV 337 13.11 EXAMPLE OF A CHRONIC INFECTION: HIV-1 337 13.12 FUTURE PERSPECTIVE 338 REFERENCES 340 14 NEURAMINIDASE INHIBITORS AS ANTI-INFLUENZA AGENTS 352 WILLARD LEW, MICHAEL Z. WANG, XIAOWU CHEN, JAMES F. ROONEY, AND CHOUNG KIM 14.1 INTRODUCTION 351 14.2 INFLUENZA NEURAMINIDASE AS A DRUG TARGET 353 14.3 NEURAMINIDASE ACTIVE SITE AND INHIBITOR BINDING 354 14.4 SMALL-MOLECULE INHIBITORS OF INFLUENZA NEURAMINIDASE 355 14.4.1 ZANAMIVIR (RELENZA) AND RELATED COMPOUNDS 355 14.4.2 LANINAMIVIR (CS-8958): A LONG-ACTING NEURAMINIDASE INHIBITOR 358 14.4.3 OSELTAMIVIR (TAMIFLU) 359 14.5 MECHANISM OF RESISTANCE 364 14.6 INFLUENZA NEURAMINIDASE INHIBITORS BASED ON OTHER SCAFFOLDS 364 14.6.1 PERAMIVIR (BCX-1812, RWJ-270201) 364 14.6.2 ABT-675 366 14.7 CLINICAL USE OF NEURAMINIDASE INHIBITORS 367 14.8 CONDUDING REMARKS 369 REFERENCES 370 15 FROM TIBO TO RILPIVIRINE: THE CHRONICLE OF THE DISCOVERY OF THE IDEAL NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR 377 ERIK DE CLERCQ 15.1 INTRODUCTION 377 15.2 THE TIBO DERIVATIVES 378 15.3 FROM LOVIRIDE TO RILPIVIRINE 380 15.4 RILPIVIRINE: HOW DOES IT ACT? 382 15.5 CLINICAL PROOF OF CONCEPT 383 15.6 PHARMACOKINETICS AND DRUG-DRUG INTERACTIONS 383 15.7 POTENCY AND RESILIENCE TO NNRTI RESISTANCE 384 15.8 CONDUSION 385 REFERENCES 385 INDEX 391
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id DE-604.BV039861286
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indexdate 2024-07-10T00:12:53Z
institution BVB
isbn 9783527326969
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language English
oai_aleph_id oai:aleph.bib-bvb.de:BVB01-024720829
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physical 1 Online-Ressource (XX, 406 S.) Ill., graph. Darst.
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publishDate 2011
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publisher Wiley-VCH-Verl.
record_format marc
series Methods and principles in medicinal chemistry
series2 Methods and principles in medicinal chemistry
spelling Antiviral drug strategies ed. by Erik DeClercq
1. Aufl.
Weinheim Wiley-VCH-Verl. 2011
1 Online-Ressource (XX, 406 S.) Ill., graph. Darst.
txt rdacontent
c rdamedia
cr rdacarrier
Methods and principles in medicinal chemistry 50
Literaturangaben
Arzneimittelentwicklung (DE-588)4143176-5 gnd rswk-swf
Viruzid (DE-588)4139555-4 gnd rswk-swf
Virostatikum (DE-588)4063598-3 gnd rswk-swf
(DE-588)4143413-4 Aufsatzsammlung gnd-content
Viruzid (DE-588)4139555-4 s
Virostatikum (DE-588)4063598-3 s
Arzneimittelentwicklung (DE-588)4143176-5 s
DE-604
DeClercq, Erik edt
Methods and principles in medicinal chemistry 50 (DE-604)BV035418617 50
https://onlinelibrary.wiley.com/doi/book/10.1002/9783527635955 Verlag Volltext
DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=024720829&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis
spellingShingle Antiviral drug strategies
Methods and principles in medicinal chemistry
Arzneimittelentwicklung (DE-588)4143176-5 gnd
Viruzid (DE-588)4139555-4 gnd
Virostatikum (DE-588)4063598-3 gnd
subject_GND (DE-588)4143176-5
(DE-588)4139555-4
(DE-588)4063598-3
(DE-588)4143413-4
title Antiviral drug strategies
title_auth Antiviral drug strategies
title_exact_search Antiviral drug strategies
title_full Antiviral drug strategies ed. by Erik DeClercq
title_fullStr Antiviral drug strategies ed. by Erik DeClercq
title_full_unstemmed Antiviral drug strategies ed. by Erik DeClercq
title_short Antiviral drug strategies
title_sort antiviral drug strategies
topic Arzneimittelentwicklung (DE-588)4143176-5 gnd
Viruzid (DE-588)4139555-4 gnd
Virostatikum (DE-588)4063598-3 gnd
topic_facet Arzneimittelentwicklung
Viruzid
Virostatikum
Aufsatzsammlung
url https://onlinelibrary.wiley.com/doi/book/10.1002/9783527635955
http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=024720829&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA
volume_link (DE-604)BV035418617
work_keys_str_mv AT declercqerik antiviraldrugstrategies