Molecular Connectivity in Chemistry and Drug Research

Medicinal Chemistry, Volume 14: Molecular Connectivity in Chemistry and Drug Research is a 10-chapter text that focuses on the molecular connectivity approach for quantitative evaluation of molecular structure of drugs. Molecular connectivity is a nonempirical derivation of numerical value that encode within them sufficient information to relate to many physicochemical and biological properties.
This book outlines first the development of molecular connectivity approach, followed by considerable chapters on its application to evaluation of physicochemical properties of drugs. Other chapters explore the application of molecular connectivity to structure-activity studies in medicinal chemistry. The final chapters provide some reflections, challenges, and potential areas of investigation of molecular connectivity.
Advanced undergraduate or graduate students in medicinal chemistry or pharmacology, practicing scientists, and theoretical chemists will find this book invaluable.

Contenu

Preface

Acknowledgments

Chapter One Structure and Properties

I. Structural Influences on Physicochemical Properties

II. Applications of Structure Definition

III. The Chemical Bond Model

IV. Additive and Constitutive Properties

V. The Need for Quantitative Molecular Connectivity

VI. Conclusion

References

Chapter Two Elements of Graph Theory and Topological Indices

I. Definitions and Terms in Graph Theory

II. Some Relationships in Graph Theory

III. The Topological Matrix

IV. Use of the Topological Matrix in Chemistry

V. Search for a Topological Index

VI. Evaluation of Topological Methods of Structure Representation

References

Chapter Three Molecular Connectivity

I. Analysis of the Randic Scheme as Originally Proposed

II. Formal Exposition of the Connectivity Method

III. Enumeration and Evaluation of mXt Indices

IV. Further Development of the Connectivity Method

Symbols

References

Chapter Four Molecular Properties and Connectivity

I. Heat of Atomization and Formation

II. Molar Refraction and Molar Polarizability

III. Gas Equation Empirical Constants

IV. Diamagnetic Susceptibility

V. Summary

References

Chapter Five Molar Properties and Molecular Connectivity

I. Intermolecular Forces Influenced by Intrinsic Structure

II. Heat of Vaporization

III. Boiling Point

IV. Liquid Density

V. Water Solubility of Organic Liquids

VI. Partition Coefficient

VII. Summary

References

Chapter Six Connectivity and Nonspecific Biological Activity

I. Drug-Receptor Phenomena

II. Anesthetic Gases

III. Nonspecific Local Anesthetic Activity

IV. Nonspecific Narcotic Activity

V. The Question of Nonspecific Drug Action

References

Chapter Seven Substituent Group Structure-Activity Relationships

I. Alcohol Narcosis of Barnacle Larvae

II. Cytochrome Conversion by Phenols

III. Enzyme Inhibitors

IV. Microbial Inhibition

V. Vapor Toxicities

VI. Sweet-Tasting Nitroanilines

VII. Summary

References

Chapter Eight Multiple Chi Terms Relating to Biological Activity

I. The Parabolic Relationship and Partition Coefficient

II. The Use of a Quadratic Expression in Chi

III. Alternative to Quadratic Expressions in SAR

IV. Summary

References

Chapter Nine Use of Physical Property Terms with Connectivity Functions

I. Inhibition of Aspergilus niger

II. The Toxicity of Diethyl Phenyl Phosphates

III. Inhibition of A. niger by Substituted Phenols

IV. Chlorosis in Lemna minor by Phenols

V. Inhibition of T. mentagrophytes

VI. Summary

References

Chapter Ten Reflections on the Nature and Future of Connectivity

I. The Formulation of

II. Interpretation of Terms

III. Comparison of Shape Characteristics

IV. Challenging Problems

V. Future Work

VI. Approaches to the Use of Connectivity in Drug Design

VII. Final Summary

References

Appendix A

I. Tables of m t Terms

II. Calculation of 1 v values from 1

III. Sample Calculation of 1 v from Tables I and II Using the S Terms from Tables III-VI

IV. Calculation of 1 from 1 v for Substituted Benzenes and Related Compounds

V. Sample Calculations of 1 from 1 v

Appendix

Index