Defined by IUPAC (International Union of Pure and Applied Chemistry) as a chemistry-based discipline, also involving aspects of biological, medical and pharmaceutical sciences, Medicinal Chemistry is concerned with the invention, discovery, design, identification and preparation of biologically active compounds; the study of their metabolism, the interpretation of their mode of action at the molecular level and the construction of structure-activity relationships. This definition exemplifies the diversity and complexity of the research activities in Medicinal Chemistry and denotes its interdisciplinary feature.

This e-Book titled Compendium of Medicinal Chemistry brings a series of articles first published in the special issue of Virtual Journal of Chemistry (in Portuguese: Revista Virtual de Química, RVQ, ISSN: 1984-6835, http://www.uff.br/RVQ/index.php/rvq), coordinated in tribute to Professor Antonio Monge, a renowned Medicinal Chemist [Revista Vir­tual de Química 2013, 5 (6), 1051-1208]. Others Medicinal Chemistry's articles published in RVQ from 2009 until 2014 were updated and selected to compose this e-Book. Readers will find fifteen chapters concerning relevant subjects in Medicinal Chemistry field, including: aspects related to innovation in pharmaceuticals; the concept of lead-compound; an introduction in molecular modeling; a review of G-protein coupled receptors; an appraisal of protein tyrosine kinases as targets for anticancer therapy; a review of Alzheimer's Disease; the role of carbohydrates in Medicinal Chemistry; quinoxaline scaffold and its use in the synthesis of bioactive compounds, and so on.

The Compendium of Medicinal Chemistry e-Book is the second of a series of electronic books, bringing together articles published in RVQ (http://www.uff.br/RVQ/index.php/rvq).

We would like to thank all the authors for their scientific contributions and the National Institute of Science and Technology in Drugs and Medicines (INCT-INOFAR, http://www.inct-inofar.ccs.ufrj.br/) for the partnership, support and for sponsored this e-Book.

To all the readers wishes for a productive and stimulating reading,

Dr Lídia Moreira Lima
Federal University of Rio de Janeiro (UFRJ)

Dr Angelo C. Pinto
Federal University of Rio de Janeiro (UFRJ)

SUMÁRIO

Preface

Opportunities and Challenges for Innovation in Pharmaceuticals
Now or Never!
Eliezer J. Barreiro, Angelo C. Pinto
1. Preamble
2. Historic Chronology
3. Pharmaceutical technological innovation: Pasteur's Quadrant
4. The capacity for innovation in the Pharmaceutical Industry (PI)
5. Contemporary innovative pharmaceuticals
6. Contribution of the National Institute of Science and Technology in Drugs and Medicines (INCT-INOFAR)26
7. Final Considerations
8. References

Molecular Modeling Methods for the Study and Design of Bioactive Compounds
An Introduction
Carlos Mauricio R. Sant'Anna
1. Introduction
2. Models
3. Comparative Methods
4. Modeling Bioligand-Protein Complexes
5. Conclusions
6. References

G Protein-Coupled Receptors
Lucas Villas Bôas Hoelz, Pedro Henrique Monteiro Torres, Guilherme Barroso Langoni de Freitas Vinícius Fonseca Leal, Tácio Vinicio Amorim Fernandes, Luiza Rosaria Sousa Dias, Magaly Girão Albuquerque, Joaquim Fernando Mendes da Silva, Pedro Geraldo Pascutti, Ricardo Bicca de Alencastro
1. Introduction
2. Structural Features of GPCRs
3. Activation Mechanism of GPCRs
4. Subsequent Activation of G Proteins
5. Classification Systems of GPCRs
6. Final Considerations
7. References

Protein tyrosine kinases
Challenges in the development of drugs aimed at cancer therapy
Carolina M. Avila, Nelilma C. Romeiro
1. Introduction
2. Structure and Function of Receptor Tyrosine Kinases (RTKs)
3. Structure and Function of Non-Receptor Tyrosine Kinases (NRTKs)
4. Tyrosine Kinase Inhibitors (TKIs)
5. Binding Modes Revealed by 3D Structures of PTKs Obtained by X-ray Diffraction
6. Monoclonal Antibodies as anti-RTKs Drugs
7. Sources of Information on PTKs
8. Conclusions
9. References

Alzheimer's Disease
Characterization, progress and implications of the neuro-inflammatory process
Flávia Pereira Dias Viegas, Kris Simone Tranches Dias, Maria Cecília Rodrigues Simões, Miguel Divino da Rocha, Maísa Rosa Castelli, Marcella Soares Moreira, Claudio Viegas Junior
1. Introduction
2. Characterization, socioeconomic impact and progress of Alzheimer's disease
3. Acetylcholinesterase Inhibitors and therapeutic arsenal available for the treatment of AD
4. Influence of the neuroinflammatory process on the outbreak and progress of AD
5. Conclusions
6. References

The Growing Importance of Carbohydrates in Medicinal Chemistry
Christiane M. Nogueira, Bárbara R. Parmanhan, Patrícia P. Farias, Arlene G. Corrêa
1. Introduction
2. Antibacterial Agents
3. Antiviral Agents
4. Antineoplastic Agents
5. Antiprotozoal Agents
6. Antifungal Agents
7. Other Agents
8. References

Beirut Reaction and its Application in the Synthesis of Quinoxaline-N,N'-Dioxides Bioactive Compounds
Lídia M. Lima, Daniel N. do Amaral
1. Definition, application and mechanism
2. Quinoxaline-N,N'-dioxide derivatives
3. Miscellaneous
4. References

Lapachol and ß-Lapachone
Two Natural Naphthoquinones with Great Importance in Medicinal Chemistry
Fernando C. Silva, Vitor F. Ferreira
1. Introduction
2. Quinones
3. Naphthoquinones
4. Lapachol (1)
5. ß-Lapachone (2)
6. Conclusion and Final Comments
7. References

MCH-R1 Antagonists as Potential Anti-obesity Drugs. Design Strategies and Structure-activity Relationship
Gildardo Rivera, Antonio Moreno, Virgilio Bocanegra-García
1. Introduction
2. Melanin-concentrating hormone (MCH)
3. MCH-R1 Antagonists
4. Conclusions
5. References

Toxoplasmosis
Perspectives on the study of new therapeutic targets
Daiana T. Mancini, Letícia C. Assis, Giovanna C. Gajo, Tanos C. C. França, Elaine F. F. da Cunha, Teodorico C. Ramalho
1. Toxoplasmosis
2. Methods
3. Results and discussion
4. Conclusions
5. References

Quinoxaline and Arylaminoalcohol Derivatives as Antiplasmodial and Leishmanicidal Agents
A Review of our First Ten Years in the Field
Miguel Quiliano, Ignacio Aldana
1. Introduction
2. Malaria
3. Leishmaniasis
4. Conclusions and Outlook
5. References

Quinoxaline 1,4-di-N-oxide Derivatives
Interest in the Treatment of Chagas Disease
Elsa Moreno-Viguri, Silvia Pérez-Silanes
1. Introduction
2. Background
3. Ten years of research
4. Complementary assays
5. Conclusions
6. Referências

Understanding the Solid Forms of 5E-phenylethenylbenzofuroxan with Different in vivo anti-T. cruzi Activity
Sara B. Honorato, Williams Porcal, Alicia Merlino, Javier Ellena, Hugo Cerecetto, Alejandro P. Ayala, Mercedes González
1. Introduction
2. Experimental
3. Results
4. Discussion
5. Conclusion
6. References

Pharmaceutical Innovation
A University Experience
Antonio Monge
1. Introduction
2. Work approaches
3. Final Considerations

The paradigm of the lead compound in Medicinal Chemistry
Eliezer J. Barreiro
1. Innovation in drugs: The process of rational planning
2. The main modern paradigm of medicinal chemistry: The discovery of the lead prototype
3. New lead compounds discovered in LASSBio
4. References