Principles of Organic Medicinal Chemistry Is Concerned with Chemistry, Synthesis, Struc- Ture Activity Relationships, Properties and Uses of Drugs of Carbon Compounds

This page intentionally left blank Copyright © 2005, New Age International (P) Ltd., Publishers Published by New Age International (P) Ltd., Publishers All rights reserved. No part of this ebook may be reproduced in any form, by photostat, microfilm, xerography, or any other means, or incorporated into any information retrieval system, electronic or mechanical, without the written permission of the publisher. All inquiries should be emailed to [email protected] ISBN (13) : 978-81-224-2485-0 PUBLISHING FOR ONE WORLD NEW AGE INTERNATIONAL (P) LIMITED, PUBLISHERS 4835/24, Ansari Road, Daryaganj, New Delhi - 110002 Visit us at www.newagepublishers.com PREFACE Principles of Organic Medicinal Chemistry is concerned with chemistry, synthesis, structure activity relationships, properties and uses of drugs of carbon compounds. This book has primarily been written with the aim of meeting the needs and interests of undergraduate and graduate pharmacy course according to syllabi of various Indian Universities. The book is a concise form covering all newer drugs will help the readers to a great extent. Though several books are available on medicinal chemistry, the material in most of them is present in a diffused form or highly specialized. In the ever expanding knowledge of the chemistry of drugs it is very difficult to go through the various textbooks, journals, and pharmacopoeias. The major objective of writing this book is to present the information in a lucid, condensed and cohesive form, to cater specially the needs of undergraduate and graduate students of pharmacy. It is impossible to express my indebtedness to those authors of various books, articles and monographs mentioned in bibliography, which became a major source of information for writing this text. I wish to recall my gratitude to Sri Y.V. Anjaneyulu, Chairman, Chalapathi Education Society, Guntur, members of Siddhartha Academy, Vijayawada, staff members of Chalapathi Institute of Pharmaceutical Sciences, Guntur, and Principal and staff members of KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada for their kind cooperation. I am also wish to acknowledge indebtedness to all who have assisted with the completion of the book. The cooperation of publishers, Messrs New Age International (P) Limited and publishers is very much appreciated in bringing out this book. The contribution that I received by sus- tained cooperation of my wife and daughter cann’t be ignored. I have made every effort to avoid printing errors. However, despite best efforts, some might have crept in inadvertently. I shall be oblished if these are brought to my notice. Con- structive suggestions, comments and criticism on the subject matter of the book will be grate- fully acknowledged, as they will certainly help to improve future editions of the book. It is hoped that the book will be received favorably as an effective text book by both students and teachers of pharmacy, science and medical scientists. Author C-8—N-CHEMI\TITLE.PM5 3 This page intentionally left blank CONTENTS 1. Introduction to medicinal chemistry ........................................................................... 1 2. General priciples of drug action ................................................................................... 3 3. Physico chemical properties of organic medicinal agents ........................................ 14 4. Chemistry of prodrugs ................................................................................................ 31 5. Drug metabolism ......................................................................................................... 41 6. General anesthetics .................................................................................................... 52 7. Sedative-hypnotic drugs ............................................................................................. 61 8. Psychoactive drugs...................................................................................................... 77 9. Antiepileptic agents .................................................................................................. 102 10. Cholinergic and anticholinergic drugs .................................................................... 121 11. Adrenergic drugs ....................................................................................................... 149 12. Adrenoreceptor blocking drugs ................................................................................ 170 13. Skeletal muscle relaxants ........................................................................................ 180 14. Antihistamines .......................................................................................................... 184 15. Narcotic analgesics ................................................................................................... 211 16. Narcotic antagonists ................................................................................................. 225 17. Antitussives ............................................................................................................... 229 18. Non-steroidal antiinflammatory drugs ................................................................... 232 19. Local anesthetics ....................................................................................................... 249 20. Diuretics .................................................................................................................... 259 21. Hypoglycemic agents ................................................................................................ 270 22. Thyroid and antithyroid drugs................................................................................. 282 Practice Questions ..................................................................................................... 290 References .................................................................................................................. 315 Index .......................................................................................................................... 317 C-8—N-CHEMI\TITLE.PM5 4 This page intentionally left blank Introduction to Medicinal 1 Chemistry The subject of medicinal chemistry explains the design and production of compounds that can be used for the prevention, treatment or cure of human and animal diseases. Medicinal chemistry includes the study of already existing drugs, of their biological properties and their structure-activity relationships. Medicinal chemistry was defined by IUPAC specified commission as “it concerns the discovery, the development, the identification and the interpretation of the mode of action of biologically active compounds at the molecular level”. Medicinal chemistry covers the following stages: (i) In the first stage new active substances or drugs are identified and prepared from natural sources, organic chemical reactions or biotechnological processes. They are known as lead molecules. (ii) The second stage is optimization of lead structure to improve potency, selectivity and to reduce toxicity. (iii) Third stage is development stage, which involves optimization of synthetic route for bulk production and modification of pharmacokinetic and pharmaceutical properties of active substance to render it clinically useful. Medicinal chemistry is the application of chemical research techniques to the synthesis of pharmaceuticals. During the early stages of medicinal chemistry development, scientists were primarily concerned with the isolation of medicinal agents found in plants. Today, scientists in this field are also equally concerned with the creation of new synthetic compounds as drugs. Medicinal chemistry is almost always geared toward drug discovery and development. Medicinal chemists apply their chemistry training to the process of synthesizing new pharmaceuticals. They also work on improving the process by which other pharmaceuticals are made. Most chemists work with a team of scientists from different disciplines, including biologists, toxicologists, pharmacologists, theoretical chemists, microbiologists, and biopharmacists. Together this team uses sophisticated analytical techniques to synthesize and test new drug products and to develop the most cost-effective and eco-friendly means of production. 1 2 General Principles of Drug Action DEFINITION OF DRUGS A very broad definition of a drug would include “all chemicals other than food that affect living processes.” If the affect helps the body, the drug is a medicine. However, if a drug causes a harmful effect on the body, the drug is a poison. The same chemical can be a medicine and a poison depending on conditions of use and the person using it. Another definition would be “medicinal agents used for diagnosis, prevention, treatment of symptoms, and cure of diseases.” Contraceptives would be outside of this definition unless pregnancy was considered a disease. All drugs have the potential for producing more than one response. Some adverse drug responses which are unavoidable are appearing at therapeutic doses are termed as side effects. Incontrast, adverse drug effects appearing at extreme drug doses are described as toxic effects. CLASSIFICATION OF DRUGS Drugs can be classified according to various criteria: 1. By origin—sources of drugs Drugs may be obtained from 1. Plants 2. Animals 3. Minerals or 4. Microorganisms. The drugs may also be semisynthetic or synthetic compounds. The sources of drugs are summa-

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