Chemistry Of Drugs (new Chemistry)

Chemistry of Drugs DAVID E. NEWTON One Last Time . . . for John McArdle, Lee Nolet, Richard Olson, David Parr, David Rowand, Jeff Williams, and John D’Emilio Thanks for the memories! ◆ Chemistry of Drugs Copyright © 2007 by David E. Newton All rights reserved. No part of this book may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage or retrieval systems, without permission in writing from the publisher. For information contact: Facts On File, Inc. An imprint of Infobase Publishing 132 West 31st Street New York NY 10001 Library of Congress Cataloging-in-Publication Data Newton, David E. Chemistry of drugs / David E. Newton. p. cm—(The new chemistry) Includes bibliographical references and index ISBN-10: 0-8160-5276-X ISBN-13: 978-0-8160-5276-9 1. Pharmaceutical chemistry—Juvenile literature. 2. Drugs—Juvenile literature. I. Title RS403.N496 2007 615.'19—dc22 2006030004 Facts On File books are available at special discounts when purchased in bulk quantities for businesses, associations, institutions, or sales promotions. Please call our Special Sales Department in New York at (212) 967-8800 or (800) 322-8755. You can find Facts On File on the World Wide Web at http://www.factsonfile.com Text design by James Scotto-Lavino Illustrations by George Barille /Accurate Art, Inc. Project editing by Dorothy Cummings Printed in the United States of America MP FOF 10 9 8 7 6 5 4 3 2 1 This book is printed on acid-free paper. ◆ CONTENTS Preface Introduction 1 2 UNDERSTANDING THE WAY DRUGS WORK IN THE BODY Early Humans Discover Drugs Types of Drugs How Drugs Work: Disease Prevention How Drugs Work: Altering Mental Processes Otto Loewi (1873–1961) The Future of Drug Design and Development Candace Beebe Pert (1946– ) NATURAL PRODUCTS The Use of Natural Products as Drugs in History Natural Products and the Rise of Modern Chemistry Robert Burns Woodward (1917–1979) Microorganisms as the Source of Drugs Marine Organisms as a Source of Drugs Plant Products as the Source of New Drugs Monroe Wall (1916–2002) and Mansukhlal Wani (1925– ) The Search for New Natural Product Drugs Natural Product Research and Biodiversity Natural Products as Dietary Supplements The Safety of Natural Products as Drugs vii ix 1 1 3 7 10 15 17 18 20 21 23 26 28 30 33 36 38 40 41 47 3 RECOMBINANT DNA AS A NEW SOURCE OF DRUGS Principles of Recombinant DNA Paul Berg (1926– ) The Process of Recombinant DNA Werner Arber (1929– ) Drugs Produced by Recombinant DNA Pharming as a Source of Genetically Modified Drugs Pharming and Transgenic Technology Pros and Cons of Pharming 4 DESIGNER DRUGS What Are Designer Drugs? Illegal Designer Drugs U.S. Drug Enforcement Administration Fentanyl Analogs Phenylethylamine Analogs Methamphetamine MDMA Alexander “Sasha” Shulgin (1925– ) Meperidine Analogs Phencyclidine Analogs GHB and Rohypnol Guesses and Risks 5 RATIONAL DRUG DESIGN: STRUCTURE-ACTIVITY RELATIONSHIPS AND COMBINATORIAL CHEMISTRY Steps in the Development of a New Drug Rational Drug Design Structure-Activity Relationships Elements of Structure-Activity Relationship Drug Design Modifications in Pharmcophores Quantitative Structure-Activity Relationships Louis Plack Hammett (1894–1987) Combinatorial Chemistry Solid-Phase Synthesis R. Bruce Merrifield (1921–2006) 53 54 58 61 64 64 72 74 77 83 85 89 90 92 94 95 96 100 104 106 108 111 114 115 117 118 123 127 131 132 134 136 138 Solution-Phase Synthesis Applications of Combinatorial Chemistry 148 156 CONCLUSION 159 Glossary Further Reading Index 163 169 173 ◆ PREFACE T he subject matter covered in introductory chem