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Pt. I General Aspects of Medicinal Chemistry Hugo Kubinyi Kubinyi, Hugo 1
1 A History of Drug Discovery Francois Chast Chast, Francois 3
2 Medicinal Chemistry: Definitions and Objectives, Drug Activity Phases, Drug Classification Systems Peter Imming Imming, Peter 63
3 Measurement and Expression of Drug Effects Jean-Pierre Nowicki Nowicki, Jean-Pierre Bernard Scatton Scatton, Bernard 73
4 Molecular Drug Targets Jean-Pierre Gies Gies, Jean-Pierre Yves Landry Landry, Yves 85
5 Drug Targets, Target identification, Validation and Screening Kenton H. Zavitz Zavitz, Kenton H. Paul L. Bartel Bartel, Paul L. Adrian N. Hobden Hobden, Adrian N. 106
Pt. II Lead Compound Discovery Strategies John R. Proudfoot Proudfoot, John R. 123
6 Strategies in the Search for New Lead Compounds or Original Working Hypotheses Camille G. Wermuth Wermuth, Camille G. 123
7 High-Throughput Screening and Drug Discovery John R. Proudfoot Proudfoot, John R. 144
8 Natural Products as Pharmaceuticals and Sources for Lead Structures David J. Newman Newman, David J. Gordon M. Cragg Cragg, Gordon M. David G. I. Kingston Kingston, David G. I. 159
9 Biology Oriented Synthesis and Diversity Oriented Synthesis in Compound Collection Development Kamal Kumar Kumar, Kamal Stefan Wetzel Wetzel, Stefan Herbert Waldmann Waldmann, Herbert 187
10 In Silico Screening: Hit Finding from Database Mining Thierry Langer Langer, Thierry Sharon D. Bryant Bryant, Sharon D. 210
11 Fragment-Based Drug Discovery Bennett T. Farmer Farmer, Bennett T. Allen B. Reitz Reitz, Allen B. 228
12 Lead-Likeness and Drug-Likeness Alex Polinsky Polinsky, Alex 244
13 Web Alert: Using the Internet for Medicinal Chemistry DavidCavalla Cavalla, David 255
Pt. III Primary Exploration of Structure-Activity Relationships Camille G. Wermuth Wermuth, Camille G. 273
14 Molecular Variations in Homologous Series: Vinylogues and Benzologues Camille G. Wermuth Wermuth, Camille G. 273
15 Molecular Variations Based on Isosteric Replacements Paola Ciapetti Ciapetti, Paola Bruno Giethlen Giethlen, Bruno 290
16 Ring Transformations Christophe Morice Morice, Christophe Camille G. Wermuth Wermuth, Camille G. 343
17 Conformational Restriction and/or Steric Hindrance in Medicinal Chemistry Andre Mann Mann, Andre 363
18 Homo and Heterodimer Ligands the Twin Drug Approach Jean-Marie Contreras Contreras, Jean-Marie Wolfgang Sippl Sippl, Wolfgang 380
19 Application Strategies for the Primary Structure-Activity Relationship Exploration Camille G. Wermuth Wermuth, Camille G. 415
Pt. IV Substituents and Functions: Qualitative and Quantitative Aspects of Structure-Activity Relationships Han van de Waterbeemd Han, van de Waterbeemd 429
20 Substituent Groups Patrick Bazzini Bazzini, Patrick Camille G. Wermuth Wermuth, Camille G. 431
21 The Role of Functional Groups in Drug-Receptor Interactions Laurent Schaeffer Schaeffer, Laurent 464
22 Compound Properties and Drug Quality Christopher A. Lipinski Lipinski, Christopher A. 481
23 Quantitative Approaches to Structure-Activity Relationships Han van de Waterbeemd Han, van de Waterbeemd Sally Rose Rose, Sally 491
Pt. V Spatial Organization, Receptor Mapping and Molecular Modeling David J. Triggle Triggle, David J. 515
24 Overview: The Search for Biologically Useful Chemical Space David J. Triggle Triggle, David J. 517
25 Pharmacological Space Andrew L. Hopkins Hopkins, Andrew L. 521
26 Optical Isomerism in Drugs Camille G. Wermuth Wermuth, Camille G. 533
27 Multi-target Drugs: Strategies and Challenges for Medicinal Chemists Richard Morphy Morphy, Richard Zoran Rankovic Rankovic, Zoran 549
28 Pharmacophore Identification and Pseudo-Receptor Modeling Wolfgang Sippl Sippl, Wolfgang 572
29 3D Quantitative Structure-Property Relationships Thierry Langer Langer, Thierry Sharon D. Bryant Bryant, Sharon D. 587
30 Protein Crystallography and Drug Discovery Jean-Michel Rondeau Rondeau, Jean-Michel Herman Schreuder Schreuder, Herman 605
Pt. VI Chemical Modifications Influencing the Pharmacokinetic Properties Richard B. Silverman Silverman, Richard B. 635
31 Physiological Aspects Determining the Pharmacokinetic Properties of Drugs Koen Boussery Boussery, Koen Frans M. Belpaire Belpaire, Frans M. Johan Van de Voorde Van de Voorde, Johan 637
32 Biotransformation Reactions and Their Enzymes Bernard Testa Testa, Bernard 655
33 Biotransformations Leading to Toxic Metabolites: Chemical Aspect Anne-Christine Macherey Macherey, Anne-Christine Patrick M. Dansette Dansette, Patrick M. 674
34 Drug Transport Mechanisms and their Impact on the Disposition and Effects of Drugs Jean-Michel Scherrmann Scherrmann, Jean-Michel 697
35 Strategies for Enhancing Oral Bioavailability and Brain Penetration Brian C. Shook Shook, Brian C. Paul F. Jackson Jackson, Paul F. 711
36 Designing Prodrugs and Bioprecursors Camille G. Wermuth Wermuth, Camille G. 721
Pt. VII Pharmaceutical and Chemical Means to Solubility and Formulation Problems Michael J. Bowker Bowker, Michael J. 747
37 Preparation of Water-Soluble Compounds Through Salt Formation Michael J. Bowker Bowker, Michael J. P. Heinrich Stahl Stahl, P. Heinrich 749
38 Preparation of Water-Soluble Compounds by Covalent Attachment of Solubilizing Moieties Camille G. Wermuth Wermuth, Camille G. 767
39 Drug Solubilization with Organic Solvents, or Using Micellar Solutions or Other Colloidal Dispersed Systems Michael J. Bowker Bowker, Michael J. P. Heinrich Stahl Stahl, P. Heinrich 786
40 Improvement of Drug Properties by Cyclodextrins Kaneto Uekama Uekama, Kaneto Fumitoshi Hirayama Hirayama, Fumitoshi 813
41 Chemical and Physicochemical Approaches to Solve Formulation Problems Camille G. Wermuth Wermuth, Camille G. 841
Pt. VIII Development of New Drugs: Legal and Economic Aspects Bryan G. Reuben Reuben, Bryan G. 855
42 Discover a Drug Substance, Formulate and Develop It to a Product Bruno Galli Galli, Bruno Bernard Faller Faller, Bernard 857
43 Drug Nomenclature R. G. Balocco Mattavelli Mattavelli, R. G. Balocco J. C. Dong Dong, J. C. S. Lasseur Lasseur, S. S. Kopp Kopp, S. 867
44 Legal Aspects of Product Protection: What a Medicinal Chemist Should Know About Patent Protection Maria Souleau Souleau, Maria 878
45 The Consumption and Production of Pharmaceuticals Bryan G. Reuben Reuben, Bryan G. 894
Index 923
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Felix Valenzuela
reviewed Practice of Medicinal Chemistry on May 06, 2013
Practice of Medicinal Chemistry
I have always enjoyed and benefited from Gazzaniga's works, both those written with Michael Sperry and those like Nature's Mind which he has done on his own. I fully expected to love this book as well, but it typifies all that is the worst in supposedly scientific exploration. What is good about this, and all his books, is that he presents studies that show where emotions, thinking, and language are localized in the human brain.
Because this book concerns itself specifically with the uniqueness of the human brain, he cites research showing what parts of the brain are activated when certain knowledge or emotions are elicited. This much is fine. However, his conclusion is always that since the human brain shows such activation, that means it is unique, that no other animal shows such activation. Unfortunately, he does not cite any research that shows that other animals' brains don't show localized arousal when stimulated by given tasks. He seems not to have heard of the ethological and cognitive studies of non-human animals despitee their timeliness and prevalence.
Moreover, he, with no justification whatsoever, makes blanket statements like "dogs feel sympathy but they don't feel pity." How does he or anyone else know this? Dogs don't have words to express emotions, but their body language, vocalizations and behavior do express their feelings and often their thought processes. Since these behaviors are consistent throughout dogdom, we can justifiably interpret certain behaviors as evincing certain feelings. Gazzaniga says that dogs don't feel guilt or shame. They act guilty only to avoid being punished. However, dogs display markedly different stances and eye contact when they are afraid, when they are trying to placate a human (as when a beaten dog crawls on its stomach, with tail and head lowered), and when they have been caught misbehaving.
I have even had dogs act as if they didn't do what they did do. One example, a dog of mine was forbidden to get on the sofa, but did when I was at work. When she heard my key in the lock, she jumped off the sofa, and crawled under it, so when I entered the room, she would be coming from underneath the sofa, yawning and stretching. Not only did I hear her jump, but she left fur on the sofa and the sofa cushion was still warm to my touch. If I then said, "What did you do?" she would adopt the guilty stance, curled body, head lowered, peering out from lowered eyes as she maintained eye contact and moved slowly in a semicircle in front of me. Those behaviors only occur when a dog has knowingly violated rules. Isn't that guilt? Couldn't it also be shame? If not, what is it? It never occurs under other circumstances, and all of my dogs have behaved the same way only when they got caught violating rules.
It is interesting that Gazzaniga lists a variety of disciplines concerned with brain functioning, but omits linguistics. Yet, linguists were pioneers in such studies since they were and are concerned with how the brain processes and produces language. My own work in schizophrenic speech (see my Understanding Psychotic Speech caused major changes in psychiatry because I showed that a dysfunction in brain processes, not Freudian constructs, were responsible for the specific language deviations characteristic of this population.
Had Gazzaniga acknowledged linguistics, as well as neurolinguistics, he would have had the definitive answer to the uniqueness of the human brain. Linguists have known for more than a century that what makes humans human is language (see Chapter 1 in my book Language the Social Mirror, 4th ed.. Note, I wrote "language," not "communication"
Language is the specific multilayered, rule-governed, context-bound system which allows all humans speaking in any language to produce a potentially infinite number of utterances, and to convey the past,present, future, the possible, the impossible, the invisible as well as the visible, the concrete as well as the abstract. Moreover, unlike animal communication and paralinguistic human communication, languages change when the environment changes. All languages also allow individuals to change language, such as Dylan Thomas's the sweethearting cribs or Shakespeare's But me no buts. Of course, if Gazzaniga had looked at linguistics or neurolinguistics, he wouldn't have had a book to write. He also wouldn't have been able to claim that all language resides in the left hemisphere, the refutation of which I will spare you.
What makes this book especially reprehensible is that Gazzaniga knows better. This is a poorly researched potboiler.
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