The Evolution of Drug Discovery

Foreword
Preface and Acknowledgment

EVOLUTION OF DRUG DISCOVERY
Antiquity
Great Periods of Drug Discovery
Vaccines

THE FIRST SYNTHETIC DRUGS AND THE BIRTH OF CHEMOTHERAPY
Aspirin, Phenacetin, and Paracetamol
Discovery of Pyrazolones
Cocaine and Local Anesthetics
Barbiturates and Related Compounds
Fathers of Chemotherapy

FROM CASUAL OBSERVATIONS TO SYSTEMATIC SEARCH
From Antihistamines to Antipsychotics and Antidepressants: The Origins of Psychopharmacology
Benzodiazepines
Structural Variations on Sulfanilamide
Azoles as a Source of Antibacterials, Antifungals, and Antihelmintics
The Long Fight Against Cancer
Sildenafil - The First Inhibitor of Rectile Dysfunction

NATURE AS A SOURCE OF DRUGS: DRUGS FROM NATURAL PRODUCTS
Plant Sources: Derivatives and Related Drugs (Selected Examples)
Animal Sources: Derivatives and Related Drugs
Drugs from Microbiological Sources
Drugs from Marine Origin: The Contribution of the Sea to the Therapeutic Arsenal

RATIONALIZING THE DRUG DISCOVERY PROCESS
Early Rational Drug Discovery Approaches: L-Dopa and L-Alpha-Methyldopa
Receptor-Based Drug Discovery
Antimetabolites in the Fight Against Bacteria, Viruses, and Cancer
Cyclooxygenase(COX) Inhibitors

STRUCTURE-BASED DRUG DISCOVERY
Searching for the Ideal Antihypertensive Agent: Renin-Angiotensin-Aldosterone System (RAAS)
HIV Protease Inhibitors
Drugs Effective Against the Influenza Virus (the Flu)
Fight Against Cancer
New Avenues for the Development of Antidiabetic Agents. Dipeptidyl-Peptidase-IV Inhibitors: Sitagliptin and Vildaglptin

BIOPHARMACEUTICALS
Monoclonal Antibodies (MAbs)
Recombinant DNA Technology (Genetic Engineering)
Some Recombinant Protein Drugs
Protein-Polyethyleneglycol (PEG) Conjugates (Protein PEGylation)

DRUG DISCOVERY IN THE POSTGENOMIC ERA: CONCLUDING REMARKS
Chemical/Genomic Strategy
Summary

Enrique Ravina studied pharmacy at the University of Santiago de Compostela, Spain, where he obtained his PhD in 1969 and was appointed Professor of Organic Chemistry in 1975. Since 1981 he is Professor of Medicinal/Pharmaceutical Chemistry at the same University. He is a member of the Spanish Royal Academy of Pharmacy, a founding member of the Spanish Society of Medicinal Chemistry and a member of the American Chemical Society. Professor Ravina has over 120 publications to his name in the field of chemistry of drugs, especially in the area of antipsychotic and cardiovascular potential drugs, including a book, book chapters, as well as a co-inventor of the world patent "6-phenyldihydropyrrolopyrimidinedione derivatives".

E. Ravina, University of Santiago de Compostela, Spain