Modern medicinal chemistry:
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| Main Authors: | , |
|---|---|
| Format: | Book |
| Language: | English |
| Published: |
New York u.a.
Horwood
1993
|
| Edition: | 1. publ. |
| Series: | Ellis Horwood series in pharmaceutical technology
|
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | XI, 290 S. graph. Darst. |
| ISBN: | 0135903998 |
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Record in the Search Index
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| adam_text | MODERN MEDICINAL CHEMISTRY JOHN B. TAYLOR, B.SC.,D.I.C.,PI..D., SENIOR
VICE PRESIDENT, CENTRAL RESEARCH, RHONE-POULENC RORER, DAGENHAM RESEARCH
CENTRE, ESSEX AND PETER D. KENNEWELL, B.A.,M.A.,PH.D., SCIENTIFIC
ADJOINT TO THE IMMUNOLOGY GROUP, ROUSSEL LABORATORIES LIMITED, SWINDON,
WILTSHIRE ELLIS IIORWOOD NEW YORK LONDON TORONTO SYDNEY TOKYO SINGAPORE
TABLE OF CONTENTS AUTHORS PREFACE 1 INTRODUCTION 1.1 DEFINITIONS 1.1.1
1.1.2 1.2 1.3 .1.3 .1.4 .1.5 .1.6 .1.7 .1.8 ^RUG 2. .2.2 .2.3
PHARMACOLOGY CLINICAL PHARMACOLOGY MOLECULAR PHARMACOLOGY MICROBIOLOGY
BIOCHEMISTRY PHYSIOLOGY AND MEDICINE PHARMACY MOLECULAR BIOLOGY
DEVELOPMENT HISTORICAL DEVELOPMENT SELECTIVITY ENANTIOSELECTIVITY THE
SCENE TODAY 1.3.1 CLASSIFICATION OF DRUGS 1.3.1.1 CNS OR
PSYCHOPHARMACEUTICAL AGENTS 1.3.1.2 PHARMACODYNAMIC AGENTS 1.3.1.3
CHEMOTHERAPEUTIC AGENTS 1.3.1.4 METABOLIC DISEASES AND ENDOCRINE
FUNCTIONS 1.3.2 INDUSTRY COMMERCIAL ASPECTS 1.3.2.1 THE EVOLUTION OF THE
PHARMACEUTICAL INDUSTRY 1.3.2.2 THE INDUSTRY TODAY 1.3.2.2.1 PRODUCTS
1.3.2.2.2 RESEARCH 1.3.2.2.3 THE DEVELOPMENT OF DRUGS 1.3.2.2.4
ACHIEVEMENTS 3 3 3 3 4 4 5 5 21 24 25 25 25 2_S 26 27 27 27 29 30 30 32
35 VI TABLE OF CONTENTS 1.3.2.2.5 PATENTS 35 1.3.2.2.6 BIOTECHNOLOGY 41
1.3.2.3 INDUSTRY-GOVERNMENT INTERACTIONS 42 1.3.2.4 THE FUTURE 45 1.4
MAJOR PROCESSES OF DRUG ACTION 1.4.1 THE PHARMACEUTICAL PHASE 47 1.4.2
THE PHARMACOKINETIC PHASE 47 1.4.3 THE PHARMACODYNAMIC PHASE 48 2 THE
PHARMACEUTICAL PHASE 49 2.1 INTRODUCTION TO BIOPHARMACEUTICS 49 2.2
PHYSICOCHEMICAL PRINCIPLES 51 2.2.1 CRYSTALLINITY AND POLYMORPHISM IN
DRUG FORMULATION 51 2.2.2 PARTICLE SIZE OF THE DRUG SUBSTANCE 51 2.3
FORMULATION SCIENCE 52 2.3.1 DOSAGE FORMS 52 2.3.2 LIQUID FORMULATIONS
53 2.3.2.1 SOLUTIONS 53 2.3.2.2 SUSPENSIONS 53 2.3.2.3 EMULSIONS 53
2.3.3 SEMISOLID FORMULATIONS 54 2.3.3.1 CREAMS 54 2.3.3.2 OINTMENTS 54
2.3.3.3 GELS 55 2.3.4 SOLID FORMULATIONS 55 2.3.4.1 TABLETS 55 2.3.4.2
CAPSULES 57 2.3.4.3 MOULDED PRODUCTS 58 2.4 ROUTES OF ADMINISTRATION OF
MEDICINES 58 2.4.1 INTRODUCTION 58 2.4.2 ORAL 59 2.4.2.1 DRUGS ACTING
LOCALLY WITHIN THE GI TRACT 59 2.4.2.2 DRUGS ACTING SYSTEMICALLY 60
2.4.3 PARENTERAL ADMINISTRATION 60 2.4.3.1 INTRAVENOUS 61 2.4.3.2 OTHER
PARENTERAL ROUTES 61 2.4.4 RECTAL ADMINISTRATION 62 2.4.5 VAGINAL AND
UTERINE ADMINISTRATION 62 2.4.6 NASAL 63 24.7 BUCCAL AND SUBLINGUAL
ADMINISTRATION 63 2.4.8 TRANSDERMAL ADMINISTRATION 64 2.4.9 PULMONARY 64
2.4.10 SUMMARY ^ 2.5 CONTROLLED RELEASE DOSAGE FORMS 67 25.1
INTRODUCTION 67 TABLE OF CONTENTS VII 2.5.2 GI TRACT DELIVERY SYSTEM 67
2.5.2.1 RATIONALE 67 2.5.2.2 MATRIX DEVICES 68 2.5.2.3 GASTRIC RETENTION
DEVICES 68 2.5.2.4 BIOADHESIVES 69 2.5.3 TRANSDERMAL DELIVERY SYSTEMS 69
2.5.3.1 INTRODUCTION 69 2.5.3.2 SKIN STRUCTURE AND FUNCTION 69 2.5.3.3
ADVANTAGES AND DISADVANTAGES OF TRANSDERMAL 69 DRUG DELIVERY 2.5.3.4
EXAMPLES OF DRUG APPLICATIONS 71 3 PHARMACOKINETIC PHASE 72 3.1
INTRODUCTION 72 3.2 ABSORPTION PROCESSES 72 3.2.1 INTRODUCTION 72 3.2.2
GASTROINTESTINAL ABSORPTION 73 3.2.2.1 PHYSIOLOGY OF THE GI TRACT 73
3.2.2.2 FACTORS AFFECTING ABSORPTION 75 3.2.3 RECTAL ABSORPTION 78 3.2.4
TRANSDERMAL ABSORPTION 79 3.2.5 INTRANASAL ABSORPTION 81 3.2.6 BUCCAL
ABSORPTION 81 3.2.7 VAGINAL ABSORPTION 82 3.2.8 LUNG ABSORPTION 82 3.3
DISTRIBUTION 83 3.3.1 GENERAL PRINCIPLES 83 3.3.1.1 AFFINITY 84 3.3.1.2
PHYSIOLOGICAL FACTORS AFFECTING AFFINITY 84 3.3.1.3 THE DISTRIBUTION
COMPARTMENT 86 3.3.2 CRITICAL FACTORS AFFECTING DISTRIBUTION 86 3.3.2.1
BLOOD FLOW 86 3.3.2.2 PROTEIN BINDING 88 3.3.2.3 MEMBRANE TRANSFER 89
3.3.3 DISTRIBUTIONS OF SPECIFIC INTEREST 90 3.3.3.1 CENTRAL NERVOUS
SYSTEM 90 3.3.3.2 THE BACTERIAL MEMBRANE 91 3.4 CLEARANCE 93 3.4.1
GENERAL PRINCIPLES 93 3.4.1.1 PHYSIOLOGICAL AND KINETIC ASPECTS 93
3.4.1.2 PHARMACOKINETIC CONSIDERATIONS 95 3.4.2 CRITICAL FACTORS
AFFECTING HEPATIC CLEARANCE 96 3.4.2.1 PHYSIOLOGICAL ASPECTS 96 3.4.2.2
METABOLIC AND BILIARY CLEARANCE 97 3.4.3 CRITICAL FACTORS AFFECTING
RENAL CLEARANCE 97 VIII TABLE OF CONTENTS 3.4.3.1 PHYSIOLOGICAL FACTORS
^7 3.4.3.2 PHYSICOCHEMICAL FACTORS ^ 3.5 SITES OF DRUG METABOLISM 3.5.1
LIVER 3.5.2 GASTROINTESTINAL TRACT 3.5.3 KIDNEY 3.5.4 LUNG 3.5.5
OTHER TISSUES 3.6 BIOTRANSFORMATION 3.6.1 INTRODUCTION XG1 3.6.2
PRODRUGS 102 3.6.3 HARD AND SOFT DRUGS W ~ 3.6.4 BIOACTIVATION 106
3.6.4.1 REACTIVE METABOLITES I06 3.6.4.2 SITES OF ACTION L07 3.7
METABOLIC PATHWAYS ^9 3.7.1 INTRODUCTION 109 3.7.2 PHASE I OR
FUNCTIONALISATION REACTIONS 19 3.7.2.1 OXIDATIONS 109 3.7.2.2
REDUCTIONS N 0 3.7.2.3 HYDROLYSIS II0 3.7.3 PHASE II OR CONJUGATION
REACTIONS 1 0 3.7.3.1 GLUCURONIC ACID CONJUGATION HO 3.7.3.2
GLUTATHIONE CONJUGATION 1 3.7.3.3 AMINO ACID CONJUGATION I 3 3.7.3.4
ACETYLATION 113 3.7.3.5 METHYLATION 114 3.7.3.6 SUIPHATION 115 4 THE
PHARMACODYNAMIC PHASE 117 4.1 INTRODUCTION 117 4.2 CELL STRUCTURES 117
4.3 THE CELL MEMBRANE 120 4.3.1 MEMBRANE LIPIDS 121 4.3.2 MEMBRANE
PROTEINS 123 4.3.3 MEMBRANE CARBOHYDRATES 124 4.4 RECEPTOR THEORIES 125
4 TYPES OF HINDING IN DRUG RECEPTOR INTERACTIONS 131 4.5.1 COVAFENT
BONDS 131 4.5.2 ELECTROSTATIC INTERACTION 132 4.5.3 CHARGE
REDISTRIBUTION 134 4.5.4 VAN DER WAALS FORCES 134 4.5.5 ENTROPY-BASED
FORCES 134 4.6 THE USE OF RADIO-LABELLED LIGANDS 134 4.7 ISOLATION OF
RECEPTORS 138 TABLE OF CONTENTS IX 4.7.1 SEPARATION OF SPECIFIC
RECEPTORS FROM MEMBRANES 138 4.7.2 PURIFICATION OF TARGET PROTEIN 139
4.7.3 THE USE OF MOLECULAR BIOLOGY 140 4.8 PRIMARY AND SECONDARY
MESSENGERS 140 4.8.1 PRIMARY MESSENGERS 141 4.8.1.1 THE NEURON 141
4.8.1.2 ELECTRICAL TRANSMISSION IN NEURONS 143 4.8.1.3 THE ORGANISATION
OF THE NERVOUS SYSTEM 144 4.8.1.4 NEUROTRANSMITTERS 147 4.8.1.5 OTHER
TRANSMITTERS 152 4.8.1.6 NEUROMODULATORS 154 4.8.2 SECONDARY MESSENGERS
154 4.9 INTRACELLULAR PROTEINACEOUS RECEPTORS 159 4.10 DNA AS A RECEPTOR
160 4.11 ENZYMES 162 4.11.1 DEFINITIONS 163 4.11.2 ISOENZYMES AND
ISOFUNCTIONAL ENZYMES 164 4.11.3 ENZYME CATALYSIS 165 4.11.3.1 KINETICS
165 4.11.3.2 GRAPHICAL REPRESENTATION 168 4.11.3.3 THE NATURE OF
ENZYMATIC CATALYSIS 169 4.11.4 COOPERATIVITY AND ALLOSTERISM 172 4.11.5
ENZYME INHIBITION 177 4.11.5.1 TYPES OF INHIBITION 178 4.11.5.1.1
REVERSIBLE INHIBITION 178 REVERSIBLE INHIBITORS: TRANSITION STATE 181
ANALOGUES REVERSIBLE INHIBITORS: MULTISUBSTRATE 182 ANALOGUES
IRREVERSIBLE ENZYME INHIBITORS 185 IRREVERSIBLE ENZYME INHIBITORS:
ACTIVE 187 SITE DIRECTED INHIBITORS IRREVERSIBLE ENZYME INHIBITORS: 188
MECHANISM-BASED INHIBITORS 4.11.6 RESISTANCE AND TOLERANCE 189 4.11.7
SPECIFIC ENZYMES 190 4.11.7.1 OXYGENASCS 190 4.11.7.2 REDUCTASES 191
4.11.7.3 HYDROLASCS 193 4.11.7.4 PEPTIDASCS 194 4.11.7.5 THE ENZYMES IN
CHOLESTEROL SYNTHESIS 196 4.11.7.6 CELL WALL BIOSYNTHESIS 197 4.11.7.7
ENZYMES AFFECTING DNA REPLICATION 198 4.11.8 CATALYTIC ANTIBODIES 200
4.11.9 RNA AS ENZYMES 201 4.11 4.11 4.11 4.11 4.11 .5. .5. .5. .5. .5.
1.2 1.3 1.4 1.5 1.6 X TABLE OF CONTENTS 203 5 DRUG DISCOVERY PROCESSES
5.1 INTRODUCTION ZT 5.2 SOURCES OF LEAD STRUCTURES 2W 5.2.1 CLINICAL AND
PHARMACOLOGICAL SIDE EFFECTS 204 5.2.2 RANDOM SCREENING 5.2.3 NATURAL
SOURCE OF DRUGS 208 5.2.3.1 PLANTS 208 5.2.3.2 MICROBES 2 5.2.3.3
MARINE SOURCES 215 5.3 MACROMOLECULAR TARGETS FOR DRUG DESIGN 217 -
5.3.1 PROTEINS AS TARGETS 218 5.3.1.1 MOLECULAR BIOLOGY AND THE
PRODUCTION OF PROTEINS 219 5.3.1.2 DETERMINATION OF PROTEIN STRUCTURE
226 5.3.1.2.1 X-RAY CRYSTALLOGRAPHY 226 5.3.1.2.2 NUCLEAR MAGNETIC
RESONANCE SPECTROSCOPY 229 5.3.1.2.3 THE PREDICTION OF SECONDARY AND
TERTIARY 232 STRUCTURES OF PROTEINS FROM THEIR AMINO ACID SEQUENCES
5.3.2 DNA AS A MACROMOLECULAR TARGET 234 5.3.2.1 ANTI-SENSE
OLIGONUCLEOTIDES 237 5.4 COMPUTATIONAL CHEMISTRY 238 5.4.1 QUANTUM
MECHANICS 238 5.4.2 MOLECULAR MECHANICS 240 5.4.3 MOLECULAR DYNAMICS 242
5.5 COMPUTER GRAPHICS 243 5.6 MODELLING DRUG-RECEPTOR INTERACTIONS 245
5.7 DRUG DESIGN METHODS 247 5.7.1 RECEPTOR FITTING 247 5.7.1.1
HAEMOGLOBIN 247 5.7.1.2 THYROID HORMONE-PREALBUMIN INTERACTIONS 248
5.7.1.3 INHIBITION OF PHOSPHOLIPASE A 2 249 5.7.1.4 THE INHIBITION OF
DIHYDROFOLATE REDUCTASE 251 5.7.2 GRID 253 5.7.3 AUTOMATED SITE-DIRECTED
DRUG DESIGN 254 5.8 APPLICATIONS OF DRUG DESIGN TECHNIQUES 256 5.9
OPTIMISATION OF LEAD STRUCTURES 259 5.9.1 HISTORICAL 259 5.9.2 LINEAR
FREE ENERGY RELATIONSHIPS 262 5.9.2.1 PARTITION COEFFICIENTS 262 5.9.2.2
ELECTRONIC EFFECTS 265 5.9.2.3 STERIC EFFECTS 267 5.9.3 USE OF THE
HANSCH APPROACH 269 5.9.3.1 TOPLISS APPROACH 272 5.9.3.2 BATCH SELECTION
METHODS 274 5.9.4 THE FREE WILSON METHOD 275 TABLE OF CONTENTS XI 5.9.5
SELECTED PATTERN RECOGNITION TECHNIQUES 278 5.9.5.1 STATISTICAL METHODS
278 5.9.5.2 DISTANCE MAPPING 279 REFERENCES 281 SELECTED BIBLIOGRAPHY
284 INDEX 286
|
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| illustrated | Illustrated |
| indexdate | 2024-07-09T17:26:29Z |
| institution | BVB |
| isbn | 0135903998 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-005871528 |
| oclc_num | 30894258 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR |
| owner_facet | DE-355 DE-BY-UBR |
| physical | XI, 290 S. graph. Darst. |
| publishDate | 1993 |
| publishDateSearch | 1993 |
| publishDateSort | 1993 |
| publisher | Horwood |
| record_format | marc |
| series2 | Ellis Horwood series in pharmaceutical technology |
| spelling | Taylor, John B. Verfasser aut Modern medicinal chemistry John B. Taylor and Peter D. Kennewell 1. publ. New York u.a. Horwood 1993 XI, 290 S. graph. Darst. txt rdacontent n rdamedia nc rdacarrier Ellis Horwood series in pharmaceutical technology Biopharmacie Chimie pharmaceutique Chimie pharmaceutique ram Medische chemie gtt Pharmacocinétique ram Préparations pharmaceutiques pharmacocinétique pharmacologie Chemistry, Pharmaceutical Pharmaceutical chemistry Pharmacokinetics Pharmacology Pharmazeutische Chemie (DE-588)4132158-3 gnd rswk-swf Pharmazeutische Chemie (DE-588)4132158-3 s DE-604 Kennewell, Peter D. Verfasser aut GBV Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=005871528&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Taylor, John B. Kennewell, Peter D. Modern medicinal chemistry Biopharmacie Chimie pharmaceutique Chimie pharmaceutique ram Medische chemie gtt Pharmacocinétique ram Préparations pharmaceutiques pharmacocinétique pharmacologie Chemistry, Pharmaceutical Pharmaceutical chemistry Pharmacokinetics Pharmacology Pharmazeutische Chemie (DE-588)4132158-3 gnd |
| subject_GND | (DE-588)4132158-3 |
| title | Modern medicinal chemistry |
| title_auth | Modern medicinal chemistry |
| title_exact_search | Modern medicinal chemistry |
| title_full | Modern medicinal chemistry John B. Taylor and Peter D. Kennewell |
| title_fullStr | Modern medicinal chemistry John B. Taylor and Peter D. Kennewell |
| title_full_unstemmed | Modern medicinal chemistry John B. Taylor and Peter D. Kennewell |
| title_short | Modern medicinal chemistry |
| title_sort | modern medicinal chemistry |
| topic | Biopharmacie Chimie pharmaceutique Chimie pharmaceutique ram Medische chemie gtt Pharmacocinétique ram Préparations pharmaceutiques pharmacocinétique pharmacologie Chemistry, Pharmaceutical Pharmaceutical chemistry Pharmacokinetics Pharmacology Pharmazeutische Chemie (DE-588)4132158-3 gnd |
| topic_facet | Biopharmacie Chimie pharmaceutique Medische chemie Pharmacocinétique Préparations pharmaceutiques pharmacocinétique pharmacologie Chemistry, Pharmaceutical Pharmaceutical chemistry Pharmacokinetics Pharmacology Pharmazeutische Chemie |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=005871528&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT taylorjohnb modernmedicinalchemistry AT kennewellpeterd modernmedicinalchemistry |