Drug selectivity: an evolving concept in medicinal chemistry
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| Other Authors: | , |
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| Format: | Book |
| Language: | English |
| Published: |
Weinheim
Wiley-VCH
[2018]
|
| Series: | Methods and principles in medicinal chemistry
Volume 72 |
| Subjects: | |
| Online Access: | http://www.wiley-vch.de/publish/dt/books/ISBN978-3-527-33538-1/ Inhaltsverzeichnis |
| Physical Description: | xvi, 519 Seiten Illustrationen, Diagramme (teilweise farbig) |
| ISBN: | 9783527335381 3527335382 |
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MARC
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| 245 | 1 | 0 | |a Drug selectivity |b an evolving concept in medicinal chemistry |c edited by Norbert Handler and Helmut Buschmann |
| 264 | 1 | |a Weinheim |b Wiley-VCH |c [2018] | |
| 264 | 4 | |c © 2018 | |
| 300 | |a xvi, 519 Seiten |b Illustrationen, Diagramme (teilweise farbig) | ||
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| 653 | |a Cell & Molecular Biology | ||
| 653 | |a Chemie | ||
| 653 | |a Chemistry | ||
| 653 | |a Drug Discovery & Development | ||
| 653 | |a Life Sciences | ||
| 653 | |a Medical Science | ||
| 653 | |a Medizin | ||
| 653 | |a Pharmacology & Pharmaceutical Medicine | ||
| 653 | |a Pharmakologie u. Pharmazeutische Medizin | ||
| 653 | |a Wirkstoffforschung u. -entwicklung | ||
| 653 | |a Zell- u. Molekularbiologie | ||
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Record in the Search Index
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| adam_text | CONTENTS
PREFACE
XIII
A PERSONAL FOREWORD
XV
PART I INTRODUCTION
1
1 POLYPHARMACOLOGY IN DRUG DISCOVERY
3
OSCAR MENDEZ-LUCIO, J. JESUS NAVEJA, HUGO VITE-CARITINO,
FERNANDO D. PRIETO-MARTMEZ, AND JOSE L MEDINA-FRANCO
1.1 POLYPHARMACOLOGY 3
1.2 MULTITARGET VERSUS TARGET-SPECIFIC DRUGS 5
1.2.1 *MASTER KEY COMPOUNDS* 5
1.2.2 SAFETY PANELS 8
1.3 POLYPHARMACOLOGY AND RELATED CONCEPTS IN DRUG DISCOVERY 11
1.3.1 DRUG REPURPOSING 11
1.3.2 COMBINATION OF DRUGS 12
1.3.3 IN VIVO
TESTING 12
1.4 POLY PHARMACOLOGY (AND POLYPHARMACY): CASE STUDIES 13
1.4.1 POLYPHARMACOLOGY IN EPIGENETICS 13
1.4.2 CHARTING THE EPIGENETIC RELEVANT CHEMICAL SPACE 14
1.4.3 POLYPHARMACY FOR THE TREATMENT OF HIV INFECTIONS 15
1.5 COMPUTATIONAL STRATEGIES TO EXPLORE POLYPHARMACOLOGY 15
1.5.1 CHEMOGENOMICS: INTERSECTION OF CHEMICAL AND BIOLOGICAL SPACES 16
1.5.2 STRUCTURE-MULTIPLE ACTIVITY RELATIONSHIPS 17
1.5.3 PROTEOCHEMOMETRIC MODELING 19
1.5.4 TARGET FISHING 19
1.5.5 DATA MINING OF SIDE EFFECTS AND INTERACTIONS FOR DRUG
REPURPOSING 20
1.5.6 SYSTEMS PHARMACOLOGY 21
1.5.7 POLYPHARMACOLOGY FINGERPRINTS 21
1.6 SUMMARY CONCLUSIONS 21
ACKNOWLEDGMENTS 22
REFERENCES 22
PART II SELECTIVITY OF MARKETED DRUGS
31
2 KINASE INHIBITORS
33
PENG WU, MICHAEL GIVSKOV, AND THOMAS E. NIELSEN
2.1 OVERVIEW 33
2.2 KINASE PROFILING 38
2.3 DEFINITION AND QUANTIFICATION OF SELECTIVITY LEVELS 40
2.4 SELECTIVITY OF APPROVED KINASE INHIBITORS 43
2.4.1 NON-COVALENT TYPE I AND TYPE II SMKIS 45
2.4.2 ALLOSTERIC SMKIS 47
2.4.3 LIPID KINASE INHIBITOR 48
2.4.4 COVALENT INHIBITORS 48
2.5 CONCLUSION AND PERSPECTIVE 48
ACKNOWLEDGMENT 49
REFERENCES 49
3 REPOSITIONING OF DRUG - NEW INDICATIONS FOR MARKETED
DRUGS
55
REN KONG AND STEPHEN T. WONG
3.1 INTRODUCTION 55
3.2 NEW USES FROM ADVERSE EFFECTS 57
3.2.1 DAPOXETINE FOR PREMATURE EJACULATION 57
3.2.2 SILDENAFIL FOR ERECTILE DYSFUNCTION 58
3.3 NEW USES BASED ON KNOWN MECHANISM OF ACTION 58
3.3.1 DULOXETINE FOR STRESS URINARY INCONTINENCE (SUI) 58
3.3.2 THALIDOMIDE FOR ERYTHEMA NODOSUM LEPROSUM (ENL) AND MULTIPLE
MYELOMA 59
3.4 NEW USES FROM GENOME, NETWORK, AND SIGNAL PATHWAY ANALYSIS 59
3.4.1 IDENTIFICATION OF SUNITINIB AND DASATINIB FOR BREAST CANCER BRAIN
METASTASIS 59
3.5 NEW USES BASED ON NEW TARGET IDENTIFICATION (OFF-TARGET EFFECTS) 62
3.5.1 ANTIDEPRESSANT DRUG, AMOXAPINE, FOR ALLEVIATING CANCER DRUG
TOXICITY OF IRINOTECAN 62
3.6 COMPUTATIONAL AND SYSTEMATIC DRUG REPOSITIONING 64
3.6.1 METHODS BASED ON KNOWLEDGE OF SIDE EFFECTS 64
3.6.2 METHODS BASED ON TRANSCRIPTOMICS DATA (TRANSCRIPTIONAL PROFILE) 65
3.6.3 METHODS BASED ON GENOME-WIDE ASSOCIATION STUDY (GWAS) 66
3.6.4 METHODS BASED ON NETWORK AND PATHWAYS ANALYSIS 66
3.6.5 METHODS BASED ON OFF-TARGET EFFECTS 67
3.7 PERSPECTIVE 68
ACKNOWLEDGMENT 73
REFERENCES 73
4
DISCOVERY TECHNOLOGIES FOR DRUG REPURPOSING
79
NAIEM T ISSA, STEPHEN W. BYERS, AND SIVANESAN DAKSHANAMURTHY
4.1 INTRODUCTION 79
4.2 BIOLOGICAL DRUG SCREENING METHODS 79
4.2.1 PHENOTYPIC SCREENING 79
4.2.1.1 ANIMAL-BASED SCREENING 80
4.2.1.2 CELL-BASED SCREENING 80
4.2.2 TARGET-BASED SCREENING 81
4.3 IN SILICO TOOLS FOR DRUG REPURPOSING 82
4.3.1 DOCKING 82
4.3.2 CHEMOINFORMATICS 83
4.3.3 PROTEIN BINDING SITE 84
4.3.4 COMBINING DRUG-CENTRIC WITH PROTEIN-CENTRIC APPROACHES 86
4.3.5 NETWORK PHARMACOLOGY 86
4.3.6 MINING OF BIG DATA 88
4.4 CONCLUSION 89
REFERENCES 90
PART III UNSELECTIVE DRUGS IN DRUG DISCOVERY
101
5 PERSONALIZED MEDICINE
103
CHRISTIAN NOE AND VOLKER BAUMANN
5.1 ROOTS OF PERSONALIZED MEDICINE 103
5.2 THE RETURN OF THE ACTIVE PHARMACEUTICAL INGREDIENTS (APIS) 104
5.3 SYSTEMS PHARMACOLOGY 105
5.4 THE PATIENT IN THE FOCUS OF RESEARCH 107
5.5 PERSONALIZED THERAPY 107
5.6 GENE THERAPY 108
5.7 REGENERATIVE MEDICINE 110
5.8 INDIVIDUALIZED MEDICINES 110
5.9 STRATIFIED MEDICINES 112
5.10 DRUG SELECTIVITY 113
5.11 SMART INNOVATION 114
5.12 ELECTRONIC HEALTH 115
5.13 DOCTOR AND PATIENT 115
5.14 THE COMPETENT PATIENT 116
5.15 CONCLUSION 117
REFERENCES 117
6 DRUG DISCOVERY STRATEGIES FOR THE GENERATION OF MULTITARGET
LIGANDS AGAINST NEGLECTED TROPICAL DISEASES
135
ANNACHIARA GANDINI, FEDERICA PRATI, ELISA ULIASSI, AND MARIA L BOLOGNESI
6.1 INTRODUCTION 135
6.2 DRUG DISCOVERY FOR NTDS: THE PAST, THE PRESENT, AND THE
FUTURE 136
6.3 SEARCH FOR NEW ANTI-TRYPANOSOMATID MTDL HITS: A PHENOTYPIC
APPROACH 138
6.4 SEARCH FOR NEW ANTI-TRYPANOSOMATID MTDL HITS: A TARGET-BASED
APPROACH 141
6.5 SEARCH FOR NEW ANTI-TRYPANOSOMATID MTDL HITS: A DRUG TARGETING
APPROACH 146
6.6
SEARCH FOR NEW ANTI-TRYPANOSOMATID MTDL HITS: A COMBINED
TARGET/TARGETING APPROACH 149
6.7 CONCLUSIONS 151
REFERENCES 152
7 DESIGNING APPROACHES TO MULTITARGET DRUGS
161
LUCA COSTANTINO AND DANIELA BARLOCCO
7.1 INTRODUCTION 161
7.2 TARGET-BASED APPROACHES FOR MULTITARGET DRUG DESIGN 163
7.2.1 DESIGNING APPROACHES FOR STRUCTURALLY RELATED TARGETS 163
7.2.1.1 FRAGMENT-BASED APPROACH 163
7.2.2 DESIGNING APPROACHES FOR STRUCTURALLY UNRELATED TARGETS 166
7.2.2.1 CRYSTALLOGRAPHY/SAR 166
7.2.22 MOLECULAR DOCKING/PHARMACOPHORE MATCHING 167
7.3 LIGAND-BASED APPROACHES FOR MULTITARGET DRUG DESIGN 170
7.3.1 DESIGNING APPROACHES FOR STRUCTURALLY RELATED TARGETS 170
7.3.1.1 FRAGMENT-BASED APPROACH 170
7.3.1.2 MACHINE LEARNING 171
7.3.1.3 SAR AROUND A LEAD 173
7.3.1.4 PHARMACOPHORE-BASED APPROACH 176
7.3.2 DESIGNING-IN APPROACHES FOR STRUCTURALLY UNRELATED TARGETS 180
7.3.2.1 FRAGMENT-BASED APPROACH 180
7.3.22 PHARMACOPHORE-BASED APPROACH 180
7.32.3 SAR AROUND A LEAD 181
7.3.2.4 MINING LITERATURE DATA 183
7.4 DESIGNING APPROACHES BASED ON PHENOTYPIC ASSAYS 186
7.5 CONCLUSIONS 189
REFERENCES 2 91
8
THE LINKER APPROACH: DRUG CONJUGATES
207
DANIEL MERK AND MANFRED SCHUBERT-ZSILAVECZ
8.1 INTRODUCTION 207
8.1.1 TARGETED DELIVERY 209
8.2 DRUG CONJUGATES 209
8.2.1 SMALL MOLECULE DRUG CONJUGATES 209
8.2.1.1 CHANCES AND CHALLENGES 209
8.2.1.2 EXAMPLES 210
8.2.2 ANTIBODY-DRUG CONJUGATES/PROTEIN-DRUG CONJUGATES 217
8.2.2.1 CHANCES AND CHALLENGES 218
8.2.22 EXAMPLES 219
8.2.3 POLYMER-DRUG CONJUGATES 223
8.2.3.1 CHANCES AND CHALLENGES 223
8.2.32 EXAMPLES 226
8.3 LINKER CHEMISTRY 229
8.3.1 DEMANDS ON A LINKER OR HOW TO LINK DRUGS 229
8.3.2 LINKER TYPES 231
8.4 CONCLUSION AND FUTURE PERSPECTIVE 233
REFERENCES 236
9
MERGED MULTIPLE LIGANDS
247
HONGMING CHEN, UDO BAUER, AND OLA ENGKVIST
9.1 INTRODUCTION 247
9.2 COMPUTATIONAL METHODS UTILIZED IN DESIGNING MMLS 248
9.2.1 BIOACTIVITY DATA SOURCES 248
9.2.2 UTILIZING KNOWN POLYPHARMACOLOGY TO IDENTIFY MMLS 248
9.2.3 APPLYING QSAR MODELS TO IDENTIFYING AND OPTIMIZING MMLS 249
9.2.4 MMLS DEVELOPED BASED ON FRAGMENTS 250
9.2.5 UTILIZING PROTEIN CRYSTAL STRUCTURES IN IDENTIFYING MMLS 250
9.3 EXAMPLES OF MEDICINAL CHEMISTRY EFFORTS OF DESIGNING MMLS IN DRUG
DISCOVERY PROJECTS 251
9.3.1 MMLS IN ONCOLOGY 251
9.3.2 MML TARGETING FOR NEURODEGENERATIVE DISEASE 255
9.3.2.1 MMLS FOR THE TREATMENT OF ALZHEIMER S DISEASE 256
9.3.2.2 MML FOR THE TREATMENT OF PARKINSON S DISEASE 257
9.3.3 MML FOR THE TREATMENT OF DEPRESSION 261
9.3.4 MMLS FOR THE TREATMENT OF CARDIOVASCULAR DISEASES 262
9.3.5 MML FOR THE TREATMENT OF DIABETES AND RELATED METABOLIC
DISEASES 264
9.3.6 MML FOR THE TREATMENT OF INFLAMMATION AND PAIN 267
9.4 CONCLUSIONS AND FUTURE OUTLOOK 269
REFERENCES 269
10 PHARMACOPHORE GENERATION FOR MULTIPLE LIGANDS
275
NORBERT HANDLER
10.1 INTRODUCTION 275
10.2 LIGAND-BASED PHARMACOPHORE MODELING 276
10.3 STRUCTURE-BASED PHARMACOPHORE MODELING 278
10.4 PHARMACOPHORE-BASED VIRTUAL SCREENING 279
10.5 PHARMACOPHORE-BASED
DE NOVO DESIGN 280
10.6 LIMITATIONS FOR PHARMACOPHORE MODELING 282
10.7 PRACTICAL STRATEGY FOR PHARMACOPHORE-BASED DISCOVERY OF MULTIPLE
LIGANDS 283
10.8 LINKED FLUOROQUINOLONE-FLAVONOID HYBRIDS AS POTENT ANTIBIOTICS
AGAINST DRUG-RESISTANT MICROORGANISMS 285
10.9 AF-PHENYLQUINAZOLIN-4-AMINE HYBRIDS AS DUAL INHIBITORS OF VEGFR-2
AND HDAC 286
10.10 DUAL INHIBITORS OF PHOSPHOLIPASE A2 AND HUMAN LEUKOTRIENE A4
HYDROLASE AS ANTI-INFLAMMATORY DRUGS 287
10.11 DUAL ANTAGONISTS OF THE BRADYKININ B2 AND B2 RECEPTORS BASED ON A
POSTULATED COMMON PHARMACOPHORE FROM EXISTING NON-PEPTIDE
ANTAGONISTS 290
10.12 DUAL-ACTING PEPTIDOMIMETICS WITH OPIOID AGONIST-NEUROKININ-1
ANTAGONIST EFFECT 292
10.13 NOVEL DUAL-ACTING COMPOUNDS TARGETING THE ADENOSINE A2A RECEPTOR
AND ADENOSINE TRANSPORTER FOR NEUROPROTECTION 292
10.14 AMINOBENZIMIDAZOLES AS DUAL-ACTING BUTYRYLCHOLINESTERASE
INHIBITORS
AND /
Z
CB2R LIGANDS TO COMBAT NEURODEGENERATIVE DISORDERS 295
10.15 DUAL ACETYLCHOLINESTERASE INHIBITORS-HISTAMINE H3 RECEPTOR
ANTAGONISTS FOR TREATING ALZHEIMER S DISEASE 297
10.16 IDENTIFICATION OF POTENTIAL DUAL AGONISTS OF FXR AND TGR5 USING
E-PHARMACOPHORE-BASED VIRTUAL SCREENING 299
10.17 ARYLBORONIC ACIDS AS DUAL-ACTING FAAH AND TRPV1 LIGANDS 301
10.18 DUAL TYPE II INHIBITORS OF TGFSS-ACTIVATED KINASE 1 (TAK1) AND
MITOGEN-ACTIVATED PROTEIN KINASE 2 (MAP4K2) 304
10.19 CONCLUSION AND OUTLOOK 307
REFERENCES 307
11 CELLULAR ASSAYS
313
YE FANG
11.1 INTRODUCTION 313
11.2 CELL-BASED MOLECULAR ASSAYS 314
11.2.1 LIGAND BINDING ASSAYS 314
11.2.2 CHEMOPROTEOMIC-BASED ASSAYS 315
11.2.3 SIGNALING ASSAYS 317
11.2.4 AUTOMATED PATCH CLAMPING 318
11.2.5 PROTEIN-PROTEIN INTERACTION ASSAYS 319
11.2.6 PROTEIN TRAFFICKING ASSAYS 319
11.2.7 CHEMOGENOMIC-BASED ASSAYS 320
11.3 CELL PHENOTYPIC ASSAYS 321
11.3.1 REPORTER GENE ASSAYS 322
11.3.2 HIGH CONTENT IMAGING ASSAYS 323
11.3.3 LABEL-FREE CELL PHENOTYPIC ASSAYS 324
11.4 SUMMARY 326
11.5 CURRENT AND FUTURE PERSPECTIVES 326
REFERENCES 327
PART IV THERAPEUTIC AREAS FOR DESIGNED MULTIPLE
LIGANDS
335
12 DEVELOPING SEROTONERGIC ANTIDEPRESSANTS ACTING ON MORE
THAN THE SEROTONIN TRANSPORTER
337
GERARD J. MAREK
12.1 5-HT TRANSPORTER-BASED MULTIPLE LIGANDS FOR DEPRESSION 337
12.2 BEYOND SSRIS: STRATEGIES TO IMPROVE UPON SSRI ANTIDEPRESSANT
ACTIVITY 338
12.3 ROSTER OF SEROTONERGIC TARGETS FOR DRUG DEVELOPED OUTSIDE OF THE
SEROTONIN TRANSPORTER (SERT) 339
12.4 PREVIOUSLY APPROVED ANTIDEPRESSANTS WITH MULTIPLE SEROTONERGIC
MOLECULAR TARGETS 340
12.5 TESTED AND FAILED/TECHNICALLY DIFFICULT DUAL-ACTING SEROTONERGIC
COMPOUNDS 347
12.6 TECHNICAL CHALLENGES TO DEVELOPING NEW CHEMICAL ENTITIES WITH
MULTIPLE MECHANISMS OF ACTION 348
12.7 CLINICAL EXPERIMENTS WITH SSRIS AND 5-HT1A
AGONISTS/ANTAGONISTS 350
12.8 CLINICAL EXPERIMENTS WITH SSRIS AND DRUGS POSSESSING 5-HT2A
RECEPTOR BLOCKADE 353
12.9 NON-SERT SEROTONERGIC TARGETS MIRED IN PHASE 2/3 355
12.10 CONCLUSIONS AND OUTLOOK 356
LIST OF ABBREVIATIONS 357
REFERENCES 357
13 MULTIPLE LIGANDS TARGETING THE ANGIOTENSIN SYSTEM FOR
HYPERTENSION
369
AGUSTIN CASIMIRO-GARCIA
13.1 RECENT ADVANCES IN THE STRUCTURAL BASIS FOR AT1 RECEPTOR LIGAND
BINDING 370
13.2 DESIGN OF DUAL ATX AND ENDOTHELIN A RECEPTOR ANTAGONISTS 372
13.3 DESIGN OF DUAL ATX RECEPTOR ANTAGONIST/PPARY PARTIAL AGONISTS 377
13.4 DESIGN OF DUAL AT1 RECEPTOR BLOCKER/NO-RELEASING AGENTS 382
13.5 DESIGN OF DUAL ATX RECEPTOR BLOCKER/ANTIOXIDANT ACTIVITY
AGENTS 384
13.6 DESIGN OF AT: RECEPTOR ANTAGONISTS WITH ADDITIONAL ACTIVITY IN
OTHER
PATHWAYS 387
13.7 SUMMARY 388
REFERENCES 389
14 MULTIPLE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-BASED
LIGANDS
397
DMYTRO KUKHTAR, MIQUEL MULERO, RAUL BELTRAN-DEBON, CRISTINA VAILS,
GERARD PUJADAS, AND SANTIAGO GARCIA-VALLVE
14.1 INTRODUCTION 397
14.2 DUAL AND PAN PPAR AGONISTS 404
14.3 OTHER MULTIPLE LIGANDS THAT ACT THROUGH PPARS 415
14.3.1 ANGIOTENSIN II RECEPTOR BLOCKERS/PPARY AGONISTS 415
14.3.2 COX INHIBITORS/PPARY AGONISTS 421
14.3.3 PROTEIN TYROSINE PHOSPHATASE IB INHIBITORS/PPAR AGONISTS 423
14.3.4 LLSS-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITORS/PPAR
AGONISTS 423
14.4 CONCLUSIONS 424
ACKNOWLEDGMENTS 424
LIST OF ABBREVIATIONS 424
REFERENCES 424
15 ANTIBIOTICS
433
JEAN-PHILIPPE SURIVET AND PHILIPPE PANCHAUD
15.1 DESIGN OF SINGLE-PHARMACOPHORE MOLECULES ACTING ON MULTIPLE
TARGETS 434
DUAL INHIBITORS OF BACTERIAL DNA GYRASE AND TOPOISOMERASE IV 434
15.1.1
15.1.1.1 DUAL INHIBITORS TARGETING THE BINDING SITE OF FLUOROQUINOLONES
435
15.1.1.2 (NON-FLUOROQUINOLONE) DUAL INHIBITORS OF DNA TOPOISOMERASES 439
15.1.1.3 DESIGNED MULTITARGET-DIRECTED LIGANDS ADDRESSING THE
ATP-BINDING
POCKET 445
15.1.2 MULTITARGET INHIBITORS OF PEPTIDOGLYCAN BIOSYNTHESIS 451
15.1.3 MULTITARGET INHIBITORS OF TYPE II FATTY ACID SYNTHASES 454
15.2 DESIGN OF HYBRID MOLECULES: DUAL PHARMACOPHORES ACTING ON
MULTIPLE TARGETS 456
15.2.1 CEPHALOSPORIN-BASED HYBRID MOLECULES 457
15.2.2 FLUOROQUINOLONE-OXAZOLIDINONE HYBRID DRUGS 459
15.2.3 FLUOROQUINOLONE-AMINOURACIL HYBRID DRUGS 461
15.2.4 FLUOROQUINOLIZINE-RIFAMYCIN HYBRID DRUGS 462
15.2.5 HYBRID MOLECULES: LIMITATIONS AND PERSPECTIVES 463
15.3 EMERGING ANTIBACTERIAL DRUGS ALLOWING MULTITARGET-DIRECTED LIGAND
DESIGN 464
15.4 CONCLUSION 465
REFERENCES 466
16 MULTIPLE LIGANDS IN NEURODEGENERATIVE DISEASES
477
JULIEN LALUT, CHRISTOPHE ROCHAIS, AND PATRICK DALLEMAGNE
16.1 INTRODUCTION 477
16.2 MOLECULAR BASES OF
ALZHEIMER
*
S
DISEASE 478
16.2.1 AMYLOID PLAQUES 478
16.2.1.1 THE ORIGIN OF ASS PEPTIDE FORMATION 478
16.2.1.2 AMYLOID PLAQUE AGGREGATION 480
16.2.2 THE AMYLOID CASCADE HYPOTHESIS 480
16.2.3 NEUROFIBRILLARY TANGLES 481
16.2.4 OXIDATIVE STRESS, NEUROINFLAMMATION, AND METAL TOXICITY 481
16.3 MTDLS DEVELOPED FOR THE TREATMENT OF ALZHEIMER S DISEASE 483
16.3.1 MTDLS BASED ON ACETYLCHOLINESTERASE INHIBITION 483
16.3.1.1 MULTI-SITE ACHE INHIBITORS AND ANTIOXIDANTS 485
16.3.1.2 MULTI-SITE ACHE INHIBITORS AND METAL CHELATORS 485
16.3.1.3 MULTI-SITE ACHE AND MAO INHIBITORS 486
16.3.2 MULTI-SITE ACHE INHIBITORS AND SEROTONIN 5-HT4 RECEPTOR
AGONIST 486
16.3.2.1 MULTI-SITE ACHE AND M2 MUSCARINIC RECEPTOR INHIBITORS 491
16.3.2.2 ACHE INHIBITORS WITH A COMPLEX PHARMACOLOGICAL PROFILE 492
16.3.3 MTDLS TARGETING OTHER ACTIVITIES RELEVANT FOR THE TREATMENT OF
AD 496
16.3.3.1 MTDLS MODULATING Y-SECRETASE AND PPARY 496
16.3.3.2 MTDL BACE1 INHIBITORS/METAL CHELATORS 497
16.3.3.3 MTDLS INHIBITING MUSCARINIC AND O L RECEPTORS 498
16.4 PARKINSON S DISEASE 501
16.5 CONCLUSION 502
REFERENCES 503
INDEX 509
|
| any_adam_object | 1 |
| author2 | Handler, Norbert Buschmann, Helmut 1960- |
| author2_role | edt edt |
| author2_variant | n h nh h b hb |
| author_GND | (DE-588)17258373X |
| author_facet | Handler, Norbert Buschmann, Helmut 1960- |
| building | Verbundindex |
| bvnumber | BV044733065 |
| classification_rvk | VS 5350 VS 5900 |
| ctrlnum | (OCoLC)1020771332 (DE-599)DNB1132349257 |
| dewey-full | 540 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 540 - Chemistry and allied sciences |
| dewey-raw | 540 |
| dewey-search | 540 |
| dewey-sort | 3540 |
| dewey-tens | 540 - Chemistry and allied sciences |
| discipline | Chemie / Pharmazie |
| format | Book |
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| genre | (DE-588)4143413-4 Aufsatzsammlung gnd-content |
| genre_facet | Aufsatzsammlung |
| id | DE-604.BV044733065 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T08:00:40Z |
| institution | BVB |
| institution_GND | (DE-588)16179388-5 |
| isbn | 9783527335381 3527335382 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-030129094 |
| oclc_num | 1020771332 |
| open_access_boolean | |
| owner | DE-11 DE-19 DE-BY-UBM DE-20 |
| owner_facet | DE-11 DE-19 DE-BY-UBM DE-20 |
| physical | xvi, 519 Seiten Illustrationen, Diagramme (teilweise farbig) |
| publishDate | 2018 |
| publishDateSearch | 2018 |
| publishDateSort | 2018 |
| publisher | Wiley-VCH |
| record_format | marc |
| series | Methods and principles in medicinal chemistry |
| series2 | Methods and principles in medicinal chemistry |
| spelling | Drug selectivity an evolving concept in medicinal chemistry edited by Norbert Handler and Helmut Buschmann Weinheim Wiley-VCH [2018] © 2018 xvi, 519 Seiten Illustrationen, Diagramme (teilweise farbig) txt rdacontent n rdamedia nc rdacarrier Methods and principles in medicinal chemistry Volume 72 Arzneimittelentwicklung (DE-588)4143176-5 gnd rswk-swf Pharmazeutische Chemie (DE-588)4132158-3 gnd rswk-swf Biowissenschaften Cell & Molecular Biology Chemie Chemistry Drug Discovery & Development Life Sciences Medical Science Medizin Pharmacology & Pharmaceutical Medicine Pharmakologie u. Pharmazeutische Medizin Wirkstoffforschung u. -entwicklung Zell- u. Molekularbiologie (DE-588)4143413-4 Aufsatzsammlung gnd-content Arzneimittelentwicklung (DE-588)4143176-5 s Pharmazeutische Chemie (DE-588)4132158-3 s DE-604 Handler, Norbert edt Buschmann, Helmut 1960- (DE-588)17258373X edt Wiley-VCH (DE-588)16179388-5 pbl Erscheint auch als Online-Ausgabe, ePDF 978-3-527-67441-1 Erscheint auch als Online-Ausgabe, ePub 978-3-527-67440-4 Erscheint auch als Online-Ausgabe, Mobi 978-3-527-67439-8 Erscheint auch als Online-Ausgabe, oBook 978-3-527-67438-1 Methods and principles in medicinal chemistry Volume 72 (DE-604)BV035418617 72 X:MVB http://www.wiley-vch.de/publish/dt/books/ISBN978-3-527-33538-1/ DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030129094&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Drug selectivity an evolving concept in medicinal chemistry Methods and principles in medicinal chemistry Arzneimittelentwicklung (DE-588)4143176-5 gnd Pharmazeutische Chemie (DE-588)4132158-3 gnd |
| subject_GND | (DE-588)4143176-5 (DE-588)4132158-3 (DE-588)4143413-4 |
| title | Drug selectivity an evolving concept in medicinal chemistry |
| title_auth | Drug selectivity an evolving concept in medicinal chemistry |
| title_exact_search | Drug selectivity an evolving concept in medicinal chemistry |
| title_full | Drug selectivity an evolving concept in medicinal chemistry edited by Norbert Handler and Helmut Buschmann |
| title_fullStr | Drug selectivity an evolving concept in medicinal chemistry edited by Norbert Handler and Helmut Buschmann |
| title_full_unstemmed | Drug selectivity an evolving concept in medicinal chemistry edited by Norbert Handler and Helmut Buschmann |
| title_short | Drug selectivity |
| title_sort | drug selectivity an evolving concept in medicinal chemistry |
| title_sub | an evolving concept in medicinal chemistry |
| topic | Arzneimittelentwicklung (DE-588)4143176-5 gnd Pharmazeutische Chemie (DE-588)4132158-3 gnd |
| topic_facet | Arzneimittelentwicklung Pharmazeutische Chemie Aufsatzsammlung |
| url | http://www.wiley-vch.de/publish/dt/books/ISBN978-3-527-33538-1/ http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030129094&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| volume_link | (DE-604)BV035418617 |
| work_keys_str_mv | AT handlernorbert drugselectivityanevolvingconceptinmedicinalchemistry AT buschmannhelmut drugselectivityanevolvingconceptinmedicinalchemistry AT wileyvch drugselectivityanevolvingconceptinmedicinalchemistry |