Antiviral drug strategies
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Schriftenreihe: | Methods and principles in medicinal chemistry
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245 | 1 | 0 | |a Antiviral drug strategies |c ed. by Erik DeClercq |
250 | |a 1. Aufl. | ||
264 | 1 | |a Weinheim |b Wiley-VCH-Verl. |c 2011 | |
300 | |a 1 Online-Ressource (XX, 406 S.) |b Ill., graph. Darst. | ||
336 | |b txt |2 rdacontent | ||
337 | |b c |2 rdamedia | ||
338 | |b cr |2 rdacarrier | ||
490 | 1 | |a Methods and principles in medicinal chemistry |v 50 | |
500 | |a Literaturangaben | ||
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650 | 0 | 7 | |a Viruzid |0 (DE-588)4139555-4 |2 gnd |9 rswk-swf |
650 | 0 | 7 | |a Virostatikum |0 (DE-588)4063598-3 |2 gnd |9 rswk-swf |
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689 | 0 | 2 | |a Arzneimittelentwicklung |0 (DE-588)4143176-5 |D s |
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700 | 1 | |a DeClercq, Erik |4 edt | |
830 | 0 | |a Methods and principles in medicinal chemistry |v 50 |w (DE-604)BV035418617 |9 50 | |
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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
|
any_adam_object | 1 |
author2 | DeClercq, Erik |
author2_role | edt |
author2_variant | e d ed |
author_facet | DeClercq, Erik |
building | Verbundindex |
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classification_rvk | VS 8750 |
collection | ZDB-35-WIC ebook |
ctrlnum | (OCoLC)780106038 (DE-599)DNB1007936916 |
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dewey-hundreds | 600 - Technology (Applied sciences) |
dewey-ones | 615 - Pharmacology and therapeutics |
dewey-raw | 615.19 |
dewey-search | 615.19 |
dewey-sort | 3615.19 |
dewey-tens | 610 - Medicine and health |
discipline | Chemie / Pharmazie Medizin |
edition | 1. Aufl. |
format | Electronic eBook |
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genre | (DE-588)4143413-4 Aufsatzsammlung gnd-content |
genre_facet | Aufsatzsammlung |
id | DE-604.BV039861286 |
illustrated | Illustrated |
indexdate | 2024-07-10T00:12:53Z |
institution | BVB |
isbn | 9783527326969 9783527635955 9783527635979 |
language | English |
oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-024720829 |
oclc_num | 780106038 |
open_access_boolean | |
owner | DE-355 DE-BY-UBR DE-861 |
owner_facet | DE-355 DE-BY-UBR DE-861 |
physical | 1 Online-Ressource (XX, 406 S.) Ill., graph. Darst. |
psigel | ZDB-35-WIC ebook FHR_PDA_WIC UBG_PDA_WIC ZDB-35-WIC FRO_PDA_WIC |
publishDate | 2011 |
publishDateSearch | 2011 |
publishDateSort | 2011 |
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 |