Wilson and Gisvold's Textbook of ANIC MEDICINAL AND PHARMAC ICAL CHEMIS TRY E L E V E N T H E D I T I N Wilson and Gisvold's Textbook of ORGANIC MEDICINAL AND PHARMACEUTICAL CHEMISTRY ELEVENTH EDITION Edited by John H Block, Ph.D., R.Ph Professor of Medicinal Chemistry Department of Pharmaceutical Sciences College of Pharmacy Oregon State University Corvallis Oregon John M Beale, Jr., Ph.D Associate Professor of Medicinal Chemistry and Director of Pharmaceutical Sciences St Louis College of Pharmacy St Louis, Missouri WILLIAMS WILKINS A Wolters Kluwer Company Bahimore • New York • London Philadelphia Buenos Aires • Hong Kong • Sydney Tokyo F4iwr: l)avid B Tiny Managing Lthsar: Matthew J Hauber Markrsing Ma,wger: Samantha S Smith Production &Iitor: Bill Designer: Doug Smock Compositor: Maryland Composition Printer: Quehecor WOrld Copyright 2(8)4 Lippincott Williams & Wilkins 351 Wcct Camden Street Baltimore, MD 21201 530 Walnut Street Philadelphia PA 19106 All rights reserved This book is protected by copyright No part of this book may be reproduced in any lOon or by any means, including photocopying or by any infortnation storage and retrieval system without written permission rrom the copyright owner The publisher is not responsible (as a matter of product liability, negligence, or otherwise) For any injury resulting from any material contained herein This publication contains infonttation relating to general principles ui medical care that should not he construed a.s specific instructions for individual patiettts Manuthcturers' prnduct information and package inserts should he reviewed lOr current information, including contraindicationt dosages, and precautions Prinle'rI in the Uniteg! Stale.s of Anwrieu First Editton, 1949 Second Edition 1954 Third Edition 1956 Filth Edition 1966 Sixth Edition 1971 Seventh Edition, 1977 Eighth Edition 1982 Ninth Edition, 1991 Tenth Edition, 1998 rswrtli Edition, (962 Llbrnry or Congrnas Cataloglng.In.Publkatloit Data Wilson and Gisvold's textbook of organic medicinal and phartnaccutical chemistry.— 11th ed / edited by John H Block John M Beale Jr p cm, Includes bibliographical references attd index ISBN 11-7817-34111-9 I Pharmaceutical chemistry Chemistry Organic I Title: Textbook of organic medicinal and pharmaceutical chemistry II Wilson Charles Owens 1911—2002 10 Gisvold Ole l904- IV Block John H V Ileak John Marlowe IDNLM: I Chemistry Pharmaceutical Chemistry Organic QV 744 W754 2ll(9J RS403 143 2111)4 IS' 19—dc2l 20031)48849 The puhlisher.s have tizade every effort to trace the c'opyri gut itolders for borrowed material If they have inadvertently overlooked any they will be pleased to make the necessary arrangements a: the first opportunity To purchase additional copies of this book, call our customer service departmenl at (800) 638-3030 or fax orders to (301) 824-7390 lniernutional customers should call (301) 714-2324 Visit Lippincols Williams & Wilkins on the Internet: htIp:// www.LWW.com Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to 6:00 pm, EST 05 06 (>7 10 l'he Fkrenth Edüion of Wilson and Gisvold's Texibook of Organic and Medicinal Pharmaceutical Charles Wilson q( Jaiine N !)elgado Chem i stry is' (kYiica:ed Iv the Jaime N Delgado 1932—2001 Delgado served as coeditor for the ninth and tenth editions and was continuing Juime N this role before his death on October 5, 200 Dr Dclgado studied with Ole Gisvold, one of the P rofessor in two founding editors of this textbook, and he was dedicated to maintaining the standards of excellence established by Gisvold and his coeditor Charles Wilson He loved teaching medicinal chemistry to students, and this textbook was a powerful aid to him A graduate of the University of Texas at Austin and the University of Minnesota Jaime Delgado began his teaching career as an assistant professor at the University of Texas College of Pharmacy in 959 He rose through the academic ranks to become professor and head of the Division of Medicinal Chemistry and a leader in research and graduate education He essentially built both the graduate program and the Division from scratch, and his publication of research and scholarly works brought national recognition to the department Although Jaime Delgado became known for his research and scholarship his first love and his greatest legacy were in teaching and advising undergraduate and graduate students The University of Texas at Austin awarded him five major teaching awards and recognized him two times as one of its "best" professors In 1997 he was elected to the Academy of Distinguished Teachers at the university and was honored as a Distinguished Teaching Professor, a permanent academic title Former dean James Doluisio described Dr Delgado's teaching style as "owning the classroom" because of his knowledge communication skills, and deep conviction that pharmacy is a science-based profession His enthusiasm and extemporaneous use of the chalkboard were legendary In addition to his contributions to teaching at the University of Texas, Dr Delgado traveled extensively in Mexico and South America to present lectures on pharmaceutical education Jaime Delgado's first contributions 10 the Textbook of Organic Medicinal (111(1 Phannaceutical Chemistry were made as a chapter author in the seventh and eighth editions Much of the material he presented came from his lecture notes Although he was proud of these contributions, which were expanded in the ninth and tenth editions, he considered his role as coeditor in the latter editions one of the highlights of his distinguished career Jaime was a true gentleman and a pleasure to have as a collaborator He will he greatly missed by the editors, authors4 and professional staff for the Textbook William A Reiners Charles Wilson 1911—2002 A s the chapters for the eleventh edition were being sent to the publisher I was notified that my colleague and friend Charles Wilson had died shortly Christmas I-Ic was a product of the Pacific Northwest having received all of his degrees from the University of Washington His first teaching job was at the now discontinued pharmacy school at George Washington University and then he moved to the University of Minnesota Charles along with other medicinal chemistry faculty at the University of Minnesota saw the need for textbooks that presented modern medicinal chemistry In 1949 he and Professor Ole Gisvold edited Organic chemistry in Pharmacy, which became the first edition of the Textbook of Medicinal and Pharmaceutical che,nix:rv Continuing in this tradition Charles and Professor Tailo Some assumed the authorship of Roger'.c Inorganic Pharmaceutical Chemistry, which included eight editions before its discontinuance Finally Charles and Professor Tony Jones started the American Drug Index series Charles continued his publishing activities after moving to the University of Texas and then assumed the position of Dean of Oregon State University's School ol Pharmacy, where he oversaw a major expansion of its faculty and physical plant Although a medicinal chemist Charles devoted considerable time to his chosen pharmacy profession students, and communily Charles was an active member of the American Pharmaceutical Association as well as the pharmacy associations in each state where he lived In addition, he was a registered pharmacist in each state where he taught: Washington Minnesota, Texas Oregon, and the District or Columbia Charles chaired national committees and sections of the American Pharmaceutical Association and the American Association of Colleges of Pharmacy Related to these, his loyalty to students included organizing student branches of the American Pharmaceutical Association al George Washington University the University of Minnesota and the University of Texas He was actively involved in the local American Red Cross blood program and took the lead in developing the hugely successful student centered blood drives at Oregon State University In 1960, Charles and his wife, Vaughn helped launch the AFS (American Field Service) in Corvallis, an international high-school exchange program He volunteered for Meals on Wheels for over 30 years after his retirement We certainly miss this fine gentleman and leader of pharmacy education and the pharmacy profession John H Block PREFACE For almost six decades, Wilson and Gisvo!d s Textbook of Organic Medicinal and Pharmaceutical chemistry has been a standard in the literature of medicinal chemistry Generations of students and faculty have depended on this textbook not only for undergraduate courses in medicinal chemistry but also as a supplement for graduate studies Moreover, students in other health sciences have found certain chapters useful at one time or another The current editors and authors worked on the eleventh edition with the objective of continuing the tradition of a modem textbook for undergraduate studerns and also for graduate students who need a general review of medicinal chemistry Because the chapters include a blend of chemical and pharmacological principles necessary for understanding structure—activity relationships and molecular mechanisms of drug action, the book should be useful in supporting courses in medicinal chemistry and in complementing pharmacology courses II is our goal that the eleventh edition follow in the footsteps of the tenth edition and reflect the dynamic changes occurring in medicinal chemistry Recognizing that the search for new drugs involves both synthesis and screening of large numbers of compounds, there is a new chapter on combinatorial chemistry that includes a discussion on how the process is automated The power of mainframe computing now is on the medicinal chemist's desk A new chapter describes techniques of molecular modeling and computational chemistry With a significant percentage of the general population purchasing altemativc medicines, there is a new chapter on herbal medicines that describes the chemical content of many of these products The previous edition had new chapters on drug latentiation and prodrugs, immunizing biologicals diagnostic imaging agents, and biotechnology Expansion of chapters from the tenth edition includes the antiviral chapter that contains the newest drugs that have changed the way HIV is treated Dramatic progress in the application of molecular biology to the production of pharmaceutical agents has produced such important molecules as modified human insulins, granulocyte colony-stimulating factors, erythropoietins, and interferons all products of cloned and, sometimes, modified human genes The chapter on biotechnology describes these exciting applications Recent advances in understanding the immune system at the molecular level have led to new agents that suppress or modify the immune response, producing new treatments for autoimmune diseases including rheumatoid arthritis, Crohn's disease, and multiple sclerosis Techniques of genetic engineering now allow the preparation of pure surface antigens as vaccines while totally eliminating the pathogenic organisms from which they are derived The editors welcome the new contributors to the eleventh edition: Doug Henry Phillip Bowen, Stephen i Cutler Kent Walsh, Philip Proteau and Michael J Deimling The editors extend thanks to all of the authors who have cooperated in the preparation of the current edition Collectively, the authors represent many years of teaching and research experience in medicinal chemistry Their chapters include summaries of current research trends that lead the reader to the original literature Documentation and references continue to be an important feature of the book We continuc to be indebted to Professors Charles Wilson and Ole Gisvold the originators of the book and editors of five editions Professor Robert Doerge who joined Professors Wilson and Gisvold for the sixth and seventh editions and single-hundedly edited the eighth edition, and Professors Jaime Dclgado and William Remers who edited the ninth and tenth editions They and the authors have contributed significantly to the education of countless pharmacists, medicinal chemists, and other pharmaceutical scientists John H Block John M Beale Jr 1st 2nd 3rd 4th 5th 1949 1954 1956 1962 1966 Wilson and Gisvold (Organic C'he,,,istrv in Pharmacy) Wilson and Gisvold Wilson Wilson and Gisvold Wilson 6th 7th 8th 9th 1977 1982 10th 1998 1971 1991 Wilson Gisvold, and Doerge Wilson Gisvold and Doerge Doerge Delgado and Remers Delgado and Remers VI, *4 A ———1 CONTRIBUTORS JOHN M BEALE, JR., STEPHEN J CUTLER, PH.D PH.D EUGENE I ISAACSON, PH.D Associate Professor of Medicinal Chemistry and Director of Professor of Medicinal Chemistry Professor Emeritus of Medicinal School of Pharmacy Mercer University Atlanta, Georgia Chemistry Department of Pharmaceutical Pharmaceutical Sciences St Louis College of Pharmacy St Louis, Missouri JOHN R.PH H BLOCK, PH.D., Professor of Medicinal Chemistry Department ol Pharmaceutical Sciences College of Pharmacy Oregon State University Corvallis Oregon PHILLIP BOWEN, PH.D Professor of Chemistry and Director Center for Biomolecular Structure and Dynamics Computational Chemistry Building Cedar Street University of Georgia Athens Georgia C RANDALL CLARK, PH.D Professor of Medicinal Chemistry Department of Pharmacal Sciences School of Pharmacy Auburn University Auburn Alabama GEORGE PH.D H COCOLAS, Professor of Medicinal Chemistry and Dean School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill North Carolina HORACE G CUTLER, PH.D MICHAEL J DEIMLING, R.PH., PH.D Professor of Pharmacology and Chair Department of Pharmaceutical Sciences School of Pharmacy Southwestern Oklahoma State University Weatherford, Oklahoma JACK DERUITER, PH.D Atlanta Georgia RODNEY L JOHNSON, PH.D Professor of Medicinal Chemistry Department of Medicinal Chemistry University of Minnesota Minneapolis Minnesota Professor of Medicinal Chemistry Department of Pharmacal Sciences School of Pharmacy Auburn University Auburn Alabama JACK N HALL, M.S., R.PH., BCNP Clinical Lecturer Department of Radiology/Nuclear Medicine College of Medicine University of Arizona University of Arizona Health Sciences Center Tucson Arizona DOUGLAS R HENRY Advisory Scientist MDL Information Systems Inc San Leandro, California THOMAS J HOLMES, JR., PH.D Associate Professor School of Pharmacy Campbell University Buies Creek, North Carolina Senior Research Professor Director of the Nutuml Products Discovery Group Southern School of Pharmacy \lcrccr University Sciences College of Pharmacy Idaho State University Pocatello Idaho TIM B HUNTER, M.D DANIEL A KOECHEL, PH.D Professor Emeritus—Pharmacology Department of Pharmacology Medical College of Ohio Toledo Ohio GUSTAVO R ORTEGA, R.PH., PH.D Professor of Medicinal Chemistry Department of Pharmaceutical Sciences School of Pharmacy Southwestern Oklahoma State University Weatherford Oklahoma PHILIP J PROTEAU, PH.D Associate Professor of Medicinal Chemistry College of Pharmacy Oregon State University Corvallis Oregon WILLIAM A REMERS, PH.D Vice-Chairman and Professor Professor Emeritus Department of Radiology University of Arizona Tucson Arizona Pharmacology and Toxicology University of Arizona Tucson Arizona ix X Coniri/nuors GARETH THOMAS, PH.D ROBERT E WILLETTI Associate Senior I.ecturer The School of Pharmacy and PH.D Auburn University Auburn Alabama Biomedical Sciences University of Portsmouth Portsmouth, England Duo Research Inc Denver Colorado FORREST T SMITH, PH.D T KENT WALSH, D.O Associate Professor Director Department of Pharmacal Sciences School of Pharmacy Nuclear Medicine Program Southern Arizona V.A Health Care Auburn University Auburn Alabama Tucson, Arizona THOMAS N RILEY, PH.D Professor of Medicinal Chemistry Department of Pharmacal Sciences School of Pharmacy System President A s—a —-—4 CONTENTS vu Preface Contributors CHAPTER Introduction fist,,: H Block a,,d Jo/u: ti! lie::!,' Jr Role of Cytochrome P-450 Monooxygenases in Oxidative Biotransformations Oxidative Reactions Reductive Reactions Hydrolytic Reactions Phase II or Conjugation Reactions Factors Affecting Drug Metabolism 67 69 103 109 111 126 CHAPTER Prodrugs and Drug Latentiation CHAP I ER Physicochemical Properties Biological Action in Relation to Joh,: H Block Overview Drug Distribution Acid—Base Properties Statistical Prediction of Pharmacological Activity Combinatorial Chemistry Molecular Modeling (Computer-Aided Drug Design) Selected Web Pages 3 C HAPIE R 26 Biotechnology and Drug Discovery 41 142 142 144 152 155 Prodrugs of Functional Groups Bioprecursor Prodrugs Chemical Delivery Systems 17 27 142 /-'orrest T Smith and C Randall C/ask History Basic Concepts 160 Jo!:,: M lfrale Jr Biotechnology An Overview Biotechnology and Pharmaceutical Care Literature of Biotechnology Biotechnology and New Drug Development The Biotechnology of Recombinant DNA IrDNA) Some Types of Cloning Expression of Cloned DNA Manipulation of DNA Sequence Information New Biological Targets for Drug Development Novel Drug-Screening Strategies Processing of the Recombinant Protein Pharmaceutics of Recombinant DNA (rDNA)Produced Agents Delivery and Pharmacokinetics of Biotechnology CHAPTER Combinatorial Chemistry 43 Daii,ỗ'la.c I? Hrs:rv How It Began: Peptides and Other Linear Structures Drug-Like Molecules Supports and Linkers Solution-Phase Combinatorial Chemistry Pooling Strategies Detection, Purification, and Analysis Encoding Combinatorial Libraries High-Throughput Screening (HIS) Virtual (in Silico) Screening Chemical Diversity and Library Design Report Card on Combinatorial Chemistry: Has It Worked' Resources for Combinatorial Chemistry Combinatorial Chemistry Terminology 43 46 48 49 50 51 52 53 54 55 58 60 60 Products Recombinant Drug Products The Interleukins Enzymes Vaccines Preparation of Antibodies Genomics Antisense Technology Gene Therapy Afterword CHAPTER Metabolic Changes of Drugs and Related Organic compounds 173 175 175 182 183 186 187 191 193 194 194 CHAPTER Immunobiologicals 65 Ste-ph:,: J C':i:ler and Jo!::: H Block General Pathways of Drug Metabolism Sites of Drug Biotransformation 160 160 160 160 162 166 167 168 169 170 172 65 66 197 Jo/ui M //eale Jr Cells of the Immune System Immunity Acquisition of Immunity 197 200 206 xi 978 Index Metubolites achy zfte 7—8 tOXiCity of 65 Metaglinides 671 Mctuhvdnn See Trichlurtoethiozide - Metaiodobenzvlguaitidinc sullate 489 Metaphen See Nitromersol Mclapmtcreno(, 536 Meraraminol 539 Metastron Set' Strontium 119 chloride Met-enkephalin 679 744 1(43—844 Mctlonnin, 672 Meihacholine, 557—558 conformations oF 555—556, 5551 Mcthacholine chloride 558—559 Methacycline hydrochlondc 345t 347 ol—).Methado(, bts-N.demethylated nietabolde of ucetylation of 122, 1231 Methadone 738, 7391 749 metaholisiti of, 85, 111Sf structure—activity relationships of 738 Methamphctamine 513 nictitholisut of 89 Methampyrime 7621 763 Methundroslenolone, 7991, 801 Methanthclinc bromide 581 Methapyrilene hydrochloride 705 Metharbital, See Mephobarhital Methaiolamide 6041', 605 6(9 Methdilarinc, 711 Mcthdilaiinc hydrochloride 711 Methcinoglobinemia 93 Melhenuinine, 253 asprodrug, 151—152, 1511 in drug delivery (56 Methenamine hippurate 253 Methenamine ittandelate, 253 Methicillin sodium, 309t 31(1 See iris Penicillin(s) Methimacole 674 metabolism of 114 Methionine 901 Methionine-enkephalin 679 744 843—844 Methocarbumol, 496 Methohexitul sodium 487 4871 Meiholrexute 41)9 414 leucosonn rescue with 4111 structure of 9421 thymidinc rescue wilh 410 Methotrimeprazine 751 Methoxamine 533 Methoxytlur.me 486 Meth,suxitnide, 5(16 Methyclothiazide 605—610, 6061 608t 620 N.Methyl-4.aminoarohenzcne, tretdatum of, 93 Methylation in drup metabolism, 125—126 (261 Methylbcn,.ethonium chloride 225 3-Mclhytcholanihrone metobolisni ol' 771 Melhylcobalunhiti 895 Meihyldihydroinorphinone 733t Methyldiphenhydramine 71)2 Methyldopa, 535 5351 metabolism of, 92, 125 Methyldopale, 535, 5351 652 Methyknc blue 227—228 Meiltylglyoxul his(guauylhydrazone) 429 Methylhydrazine 397 relative activity of 8091 Minipres.' Set' Prazosin sotuhilily of Mittocin, Set' Minocycline hydrochloride Minocyclinc hydrochloride 3451 348 Minoxidil 654, 655 metabolism of 84 Miiitezol See Thiabcndaiasle Miradon See Anisindionc Mirena See l evonorgesttet-releasing intr,iuterine system Mirtazitpinr 520.541 Misoprostol 126 827—828 Methylprednisolone sodium succittate solubility of, sU'uctuuv of 77(1 Methylrosaniline chloride 227 Methyl solicylute 754 l7o-Mcthyltcstosterone, 798 7991 801 biological activity ol' 798 7981 hepatolovicity of 798 structure—activIty relationships for 798—799 79t)t structure of 77(1 799f Methyl-ThFA trap hypothesis 895 Methyliraitslentacs 125 Methyl violet 227 Methylsunthunes 5(0 511—512.51 Ii Metiaiuide metabolism of 99 11)1 Mctipraiiolol 543 Metucunne iodide, 591 Mctnln,onc 61)7—610 6071 (419t 620 Metoprolol 544 545.5451 active metabolites 1351 nsctabolistti of 77 98 Metnwole Sr.' Pentylenetctra,ote Metrilonate, 567 Metneamide 483—484 Metro IV See Metronidacole Metrottida,.ole, 260—261 metabolism of 1(17 Metyrupone metabolistit of 1051 Metyrosine 528 Mevacor See I,.ovastatin Mevristutin 662 Menilctine hydrochloride 641) Mexitil Set' Mexiletine hydrochloride MeLOn See Me,.locillin sodium Meulocilliti See also Penicillin(s) spectrum 0) aclisity of 308 Meelorillin sodium 309* 3(4 Mibcfr.tdiI 945 Micurdis See Telmisariun Micatin See Miconaeole nitrate Michael addition reactions (20 Miconazole nitrate 242 Microbial resistance 31)1 3(15—307 335—336 Microchip spatial arrays, in combinatorial synthesis 44 451 60 Micronasc See ('ilyburide Microride, Ste Hydrochlornthiaeide Midamor Set' Amiloridc hydrochloride Mudazolam a' anesthetic, 487 Midodrine 533 Mifepnstone 795, 7951 Mifiprex See Mifepristone Miglitol 672—4.73 MIH See Procarba,ine hydrochloride MMFF94 Force Field 925—926 MMR vaccine 211 212t MNDO method 938 Moban Sit' Mohindone hydrochloride Mohic See Meloxicam Mobidin See Magnesium saticylate Modafinil 5(0 Moduretic See Atniloride.hydrochlonithia,ide Molar reactivity (MR) 21 2lu Molecular connectivity, 24 24t Molecultir diversity, quantification of 56—58 Molecular dynamics sitttuluiions 933—935 Molecular mechanics, 3(1 Molecular nixxleling hull-and-spring models in 923—929 See also Force field iiiethods computer-assisted 27—41, 919—922,9211, 9221 See ii! , ('ompstier-assisted drug design ('PlC models in 920 921—922 physical 920 solvent-accessible surfaces in 922 van der Waals surface in 922 9221 Molecular orbital calculations, 935 Molecular similarity, quantification of 56 57t Molecular structure drug—receptor interactions and 31—34 physiologic activity and 11—21 28 31—41 Molindone hydrochloride 502 Molyhdenum.99 production trl 462 462f, Miltown See Meprobam-ate Monoacylureas 51)6 MINIX) method 938 Mineraloconicoid(s) See also Steroid(s) biological activities of, 81(5 Monoamine oxidase inhibitors (MAOIs) 5(4—5(6 51St Monoamine i)tidaccs (MAlls) 90—91 exccs.s of, $05 modifications of, 806—807 806t products 8071, 810—811 relative activity of, 809 809t structur.il classes at' 8(16—809 struchitre—activity relationships, for 807—808 Meiliylprednisolone 8(11(1 Mitrobronliol 395 Mivacron See Mivacanum chlonde Mivacurium chloride, 593 Mixture library 43 441 MM2 force field 927 MM3 force field 925—926 927 MM4 force field 925 —926 Moinetasonc t'uroatc 8(3 814, 8141 Monisiat, See Miconucole nitrate N.Methylmorphinan 738—739 742 Mctltylnitrnsurea 395 398 Mcthylplienidate 514 netabolisun uI 89 1(11 11(9 Mltoguazone 429 Mitomycin C lIMIt, 4(4 423—424 activation of 152—153 1531 397 397f Mitomycins 419—420 Milusis 391 3911 Mitoiane 436 as tintincoplastic, 435 Mitoxantrone hydrochloride 429 432 914 Mtlk Millon's test, 834 Miloittm See Pliensunlittide Milrin.me (.57 Methyl ioidide toxicity of I (K—I 19 Methylparaben, 228 —229 Mithrurin.Si'.' Plicamycin Mithrainycin See Plicamycin 11071—%08f 8091 structure of $071 Miner.iloconicoid receptor antagonists 1115 Mineralocorticoid receptors, 773 4631 526—527 5261 Mon,.umine reuptake inhibitors 5(6 Monobavtaiits 334 Monocid See Cefonicid sodium Monoclatc-P.Sr'e Antihemophilic factor Monoclotiat antibodies, 181—191 as untineoplastics 442—444 chiuneric (89 diagnostic 471) preparation of 187 Fader in rudionuclide lest kits, 190—191 therapeutic, 191 types ol, 119—191 Monocytes 198—199 1991 Mononine See Factor IX recombinant Monoprit See Fosinopril sodium Moricirine, 1,40 Morphine and related compounds 731 —753 addictive liability of 732 733 744 discovery isl, 744 historical perspective on 733 indications for, 744 metabolism of 85—86 86 87 98 112 126 modifications of based on Grcwc's research, 738—741 based on Isleb and Schat,mnnn's research 735—738 based on Small and Eddy's research 733—735 early 733—74 I pharntacologic properties of 744 preparations of 744—745 products 744—751 receptor i,twraction.s with 74 1—743 7421 743? solubility of 744 source of 744 struclure—uctivity relationships (or 733—735, 734t—735t 741—744 synthetic derivatives of 733 Morphine hydrochloride 744—745 Morphine sulfate 745 Morse curve 925 9251' Mosquito control, for malaria, 282—283 Motilin 855 Mottr tterves 548 Motor tteuron, 680 Mottin See Ihuprofen !sloxalactajn, 325 mRNA 162 Mucosal immunity 200 Mucus 200 Mulliken population analysis 939 Multillance See Gadobenate meglumine Multiple sckrosis 181—182 Mumps vaccine 211, 2l2t Munurol See Fosfomycin tromethaminc Mupirocin 362—363 Muromonab-CD3 190, 859t Muscarine activity ol, 556 isomers ol, 556, 5561' structure of, 5581' Muscarinic antagonists 558—572, 559f Muscarinic receptors, 5511—553, 55 If, 5521 ucelylcltoline and 557—558, 557f, 557t structure of 557—558 5571 557, subtypes of 551—552 Mustargen See Mechlorethamine hydrochloride Mutamycin See Mitomycin C Muzolimine, (ils—616, 6151 Myantbutol See Mycelex See Clotrima,ole Mycifradin See Neomycin sulfate Mye'ohas':erium avium, 254 Alveobacterium insracellularc 254 Mvcobactc'riun, Lansa.rii 254 Mycabacterrurn leprac 254 279—281) Mycabacrr'riunr rubercu!osi.c, 254 Mycoses See Fungal infections Mycostntin, Ste Nystatin Mydriacyl See Tropicatnide Mydnatics 573—574 Myelin, 679 Myelogrsplty 480 Mycloid cells, 197 981 Mykrox See Metolazone Myleran See Busulfan Mylotarg See (iemturumab ozogarnicin Myocardial ischemia, 622—623 6231' Myocardial metabolism 622—623 6231 Myoscint Kil See lmcirutnab pentetate Myosin, 623 6241 Myrtccainc 6941 Mysoline See Primidone Mytelasc chloride See Arnbenonium chloride N Nahilone, metabolism of, 1051 Nabumetone 759 as prodrug 152 NAD 888—889 8891 NADH 889 Nadolol, 543, 5441 NADP 888—889 8891 Nafantostat 447 Nafcillin codiutn, 3091 311—312 See a/co Penicillin(s) Naftitinc hydrochloride, 239 Nautin See Naftifine hydrochloride Naja venom solution 835 Nalhupltine, 743, 746, 750 Nallon See Fenoprofen calcium Nalidinic acid 247 248, 248, Nalntefene hydrochloride 752 Nalorphine hydrochloride 735 740 743 751 Naloxone hydrochloride, 740, 751 metabolism of, 11)51 740 741, 751—752 metabolism of, 105 Nandrolone decanoute, 7991', 801 Nandrulone phenpropionate 7991 801 Napltazolitie, 533 Naprosyn See Naproxcn Naproxen 759 ,netabolis,u of, 114 Naqua See Trichlortnethiazide Narcan See Naloxone hydrochloride Narcotic analgesics 731—753 Ste also Analgesics: Morphine and related compounds metabolism of 87 Narcolic antagonists, 740—741 structure—activity relatioitships for 743 types of 751—752 752, Narcotic antitussicca 752 Nardil Sec Phenclzinc sulfate Nasricort See Trinincinolone acetonide Nasarel See Flunisolide Nasonex Sec Mometasone Iun,ute Natacyn See Natamycin Natumycin 237—238 Nateglinide 671 National Cancer Institute, drug screening protocol of 392—394, 3931 Natur.,l products, combinatorial synthesis of 47—411 471 Naturetin See Bendroflumethiazide Navane See Thiothixene Navelbine Sec Vinonrlbine Imitate Neaminc 338 Nebcin See Tobramycin sulfate Nehrsmycins, 340 NebuPent See Pentamidine isetbionate Nedocromil sodium 715, 716 Nelazodone 19—520 Nefrolan See Clorexolone Negorum See Nalidixic acid 979 NeIfi,tavir 385—387 development of 942 9431 fslembntal, See Pentobar'nital sodium Neobiotic See Neumycin sulfate Neomycin sulfate 338 Neonatal hyperbilirubineniia I IS 26 Neosamine 338 Neostigmine bromide 5631, 564 56.41 Neostigmine melhylsulfate 565 Neo.Syttephnne Sec Phcnylcphrine Nepltrun active ttuhular secretion in, (iOl —602 (,02f function of in edematous states, 601 in hypovolemic states 601 in nomtovolemic states 596—601 5981—61)01 intercalated cells of, 6(10, 6001 principal cells of, 600 6001 sodium reabsorption in 597—601 structure of, 596 5971 Ncptazane See Methazolamidc Nerve(s) fltotoi 548 somatic 548 Nerve blocks, 6117 Nerve cells 679, 6791 Nerve fibers, 679-680 6801 Nerve impulse, transmission of, 680—681, 6801 6811 683 Nervous system divisions of 548 structure and function of, 679—685 Netilmicin sulfate 340—341 Netrontycin See Netilniicin sulfate Neumega See Oprelvekin Neupogen See Filgrastim Neurohoritiones, confomtatiottal flexibility of, 34—35 341 Neurohypophyseal hormones 1145 Neurohypophysis 841 Neuroleptics 496—503 Neuromuscular blocking agents 589—595 curarcicttrare alkaloids 590—591 dcpolarieing 590 nondepolarizing, 589—590 synthetic compounds with curariform activity 591—595 Neuromuscular junction 5119 Neurons, 679, 6791 motor, 680 Nearontin See Gabapentin Neurotensin, 1155 Neurotrunsinitters, 683—685 acetylcholine as 548 adrenergic 524—547 Sec also Adrenergic neurotransmitters drug effects on 684 excitatory (184 ganglionic stimulation by 586, 5871 inhibitory 684 release of 1,83, 61141 structure of 683, 684t Neutralization, in immune response 205 Neutralizing allosteric niodulutors, 489 Neutropltils 197 19Sf, 2t10 Nevirupitte 383 Newton.Raphson geometry optimization approach, 930 Newton's laws of motion 933—934 Newton's third law, 924 Nexium See Esomeprazole magnesium Niacin 888—890 See also Nicotinic acid as antilipidetitic 661 890 metabolism of, 126 980 lnth'x Niacinamide 890 Nicalex See Niacin Nicardipine driwhloride 63 —632 Niclo.amide 266 Nicotistamide adcn,ne dinucleotide (NAD) 888-88') 1(891 Nicotinaznide ideniiie dinuckotide phosphate )NADP) 888—81(9, (4891 Nicotine 51(7—5(48 ittetalmlism oF 87 93, 11)1 126 Nicotinic acid, 888—890 as antilipidcnaic 661, 890 metabolism of, 26 Ntciitiiiic receptors 548—550, 549f 5491 Nifedipiric 6291 630—631 6311 Nifurtimox, 263 Night blindness, 8711 Nil-I shift 71 721 Nilandron, 5cr Nilutatnide Nilutamide, 437 801—8112 11021 antineoplastic 434 Nim.idipinc 632 as Niminop See Nirnodipine Ninhydnn test 834 Niprtde See Sodium nitmpnisside Nirsanin 677 Nisoldipine, 632 Nisosctine, 519 Nitr,utcv Set' Nitruvasodilators Nitr.m'iepatmm inelabolisiit of 107 632 Nitric acid esters, 625 Nitric imuide formation 01 624 siwlana and 283 iii sniooth nmuscle relaxation, 624—625 6241 Nitrites Sir Nitrovasodilators Nitro commmpounds metabolism of (07— 108 Nitn,funms 252—253 Nitrofur,mnloin 252 253 Nitrofuruzone, 252—253 Nitrogen tmtustani 394 399—4(81 Nitrogl5cerin 625—626 (.251 metabolism of, 12(1 625 Nmlmmcr,iol 228 Nitnmprecs Set' Sodiuni mU'uprusside Nitroso compounds See Nitrovusodilators Nitnisureas 395 398 Nitrous acid esters, 625 Nitrous oxide, 486—487 Nitrova,sodi(ators antianginal action of 625—626 niechanisin of action oh, (.22—623, 6231, 624 6241 of (.23—624 625, 62Sf nil.ic oxide release by 625 i)SldiIIi(ifl State,, (ii 625t speed and duration of action of 61St structufe—aesivity relationships (or 6151 625 types oF (.26—627 (.261 Nivalin, See Nix See I'crmcthrin 7(91 720, 720t 722 Nizoral See Ketoconazole n.octauol/water system drug partitioning in tY—20 Nodes of Raitvier 679, 6791, (.81 Nofetunmontab nierpentan 190 Nonsleroidal anti.influmniatory drugs Nuprin See Ihuprolen Nurum.i S,'c us analgesic, 753—763 See also Antiinflammatory analgesics chloride Nutritional factors, in drug mnemabolism 131 t32 944—945 &mruehidonmc acid metabolism and 822 Nuvaking Set' Itionogestrel (NSMDs) mechanism of action of 8(8 Nimr.ukenuline, Ste Norepincphrinc Norchloreyclirinc 706 Noreuron See Vecumnium bromide Nonlazepato 490 Norelgestroinin 7871 789 Norephedrine metabolism of (26 Norepinephminc 524—547 adrenergic receptors and 527—528 biosynthesis of 524—525 524f in local anesthesia 688 properties of 524 structure oF 524 as sympathomimetic 532 uptake and metabolism of, 525—527 5261 Ntmrethindrone, 786t, 7871, 789 in contruccptivcs 7911—7921 in horrnonc replacenment therapy 796—797 7961 metabolism of (06 Norcthynndrcl 786t, 7871 789 Nortlc* See Orphcnadnne citrate Nmmrlloxacin 248 2481, 249 Norgestimame 7871 789 in eontr.mceplisc 792t in hormone replacement therapy 796-797 796t Norgestrel 7861 787f 789 in contraceptives 79lt ntctabolisn, of 11)1 Norkciamine, metabolism of 89 Normethadone, 7391 Normodyne See Labmitalol Normorphinc, 741 747 Noroxin See Nortloxacin Norpace See Disopyramide Norplant 793t 794 Norpramin See Desipramine hydrochloride (9.Nu,flestimstcmne derivatives 786, 786t Noetriptylimte 5(7 as active merabolite, (34 l3St Noreasc See Atnlodipine Norvir See Ritonavir Noscapinc 752—753 Notee See Chkrrul hydrate Novaldeit See Tanmoxifen Novuntrone See Mitoxantrone hydrochloride Novatropine See l-lnmuu'opine methyibromide Novobiocin sodium, 361—362 Novocainc See Procaine Novolin See Insulin, recombinant Novolog See Insulin, recombinant Novo Seven, Factor VIm, recombinant NPH insulin, 8511, 852 1(521 NR geometry optimization approach 930 NSAIDs See Nansteroidal anti.iullammutory drugs CNSAIDsI Nuhain See Nalbuphsnc Nuclear magnetic resonance spcclroscopy of proteins 832 Nuclear medicine, 455 458—462 Nucleic acids See RNA Nucleon, 455 Nyctimlopia 871) Isoitiaiid Nystatin 237 3(88 (3 9,1 tl-Octadecm,miismnmide as sleep.tnsntmimting agemtt 48)1 ,m.Oviaimiml/waier system, drug parlituiiiiiig in t9—20 Octri,otide acetate, 1145 Oculcn.Sm'e l'hurhmprmilemm (kupress Si-i' Canemilol Ollonacin 2411, 248 254) Oil of wintergreen 754 OK'l'3 Se.' Muronmimah'CD3 Olan,.ipinc, 51)2 Oleammdohidmi 353 Oleammdotnycin 353 Olcfmns oxidation of 74-77 2' 5'.Oligoadenyhate symithemase 2(12 Olivm.myciims 4(7 Olsala,ine enzymatic depredation of as prodrug 4-S Ommieprazole 722—724 723i activation of ISS lsf.b Omnnipen Ste Ampicillin Onini,.can Sec Gadimiliantide Oncimgenic viruses, 372 OncimScisil nmurine Sm'.' Saiminutmuab pendetide ()ncnvin See Vincrisiinc satIate One.bL'ad one-conipiiund synthesis 46—411 54 62 Ontak See l)enileukmn dilsitox Opiophohia 731 Opium 732 747 Oprelvekimm, 183 Opiical isomers bimdi,gical ictisiiy ol 35—37 351 361 Optiittark Si'.' Gadoversetaniide Optinmine.Sei' A,atadmne nialeate Optsntizaticin proceshimres, 58 (.)ptiPranolol Sr-c Metipranimlol Optisiir Si-c Azela.stine hyilrcmchiloride itplitlmiilmmiic solution Or.i( administr,itiimn drug distribution in, 3—S 4f Oral coimlraceptives See ('oniraceptives Orange oil 229 Oresic.Si'i' flydroclmlorothiazide Organic nitrates Si-i' Organic mmjtrites, Si'm' Nitnn'itsislitaiors Organoniercuri.mls mnti.inlectusc 228 diuretic, 610 Orina.se See Tolbutaniide Onnuse l)itignmr.iic Sri' Tolhuianimde sodium Ormaplatirm 4214 Ornidyl See Efloriiitliine Orphienadrine imietabmilism mit 147 Orphenadrmnc citr,ime,5142-583 Orthocainc 677 Orthocli,ne-OKT3 See Mun,mnonab-('l)3 Nucleoproleimms 835 Orilmo-Eura Ste Nimrelgestronhmn Nog&mlamriycin 416—417 Nucleoside antifunguls, 235 Orih,mforni See Orihuicaine Nolvadex See Tamoxifen Nminnucleoside reverse Iranscriptase inhibitors Nucleoside antinmelabolites 372 375—379 Nuclmrscrntes 835 Orthmmgonah pooling, in eoimtbimtatoeial Nuclidc 455 Nnmorphan See Oxymorphone Nupercaine, 678 Orthmo.Preimisi Sri' I lomimine replucemmicnl 383— 384 Nonselective norepinephrine reuptake inhibitors 519 clteittisimy Sit—SI 62 therapy Orudic Sm-c Ketoprolcmi ()sniuirtil Si" Maiuiiitti) Oirisun Sec Xyliinieias'oliiie Ovulation, regulation at 774 7141 Osacillin sodium 3i19i ill Sic tiloi Papase Sic Papaiti Papaverinr 586 732 aiiiispasniixlic activiiy of 574 624 iiieiabcilisiii cii 133 Peuiicilliiiisi Osalid 763i Onaliplatin, 428 Oxaiiiiiiqiiiiie 266—267 Oxandrin See Ovaiidrol,iiic Onandrolone 799) 11111 Oxapr.iein 760 Paper chrcnnatiigrapliy 83.) Parabens See p-Ilydro.svben,oic acid Paraldehyde, 496 Paraniagiieiic contrast ugenis 475-477 476i Osai.epaiii 491 Parasvinpadietic agenki 572—574.5cc into' (')tiilcnergic blocking agenis Panasympaiiici)yiic ageiitr Sec Otitliicergic blocking agents Par.isympathomiioeiics 54$ is active iiictaholite, 134, 135i itieiattolism itt 133 Ovaaolidinediones 505 Oxiord unit 302-3113 Oxiconacaile tiiiraie 242 Onidiiiiiin in hiotranslorniaiiiin Sic I)rxig nieiatiolisni ovidatiiin in pniiein, 73 74) Oxidaiis e I lit Paraplalin Ste ('ar)xiplaiin Parasyinpailieiic gaiiglia 586—587.587) Parasyiiipaihciic len-lids sysieni 518 Parathion 5711 iiietabiitisin 99 Par.itliyriiii) horniiine 85.5—856 iiieialritlism 'il Ill Oxidatise deantinalion 89 in vitamin I) synihesis, 876 Par.iths raid injeciiiiic 855 Osidaiive detiattigeiiaiioii 1(11 - 1113 l)xidaiise deliydriigenatioii I lit 85 Osidatixe Parenterul adniinisiraiicin drug distrihuiuiin in Oxidicing agenis 223 Oxine 261 l)xistai See Onicona.iole iiiicaie Oxisuran, ineiaholisin cii, 14)5—1)16 Oxoinenitirine 55)1, 5581 Oxy-5 See Hydrous hencoyl peroside Oxy It) tt' Hydriiiis beiieoyl tieriixiile Oxyhuprocaine hydrochloride 690—693 691i Oxychlcircisene sodium, 124 Oxycodiiiie 733 733t Oxyciicliine hydroctiloride 746 Oxy-Coniin.St'i' l)xyciidtine hydriictiliiride Oxyiiieta.iciline 533 Oxymeiliolinie 7991 8(11 Oxynnirphone 733 733i 746 Onyphenhutueaine as active nierabciliie I 14 135t O.xyp)iencycliiiiiiie liydrociitiiriile 581 582 Oxypreiiiiliil ineiabolisiii •i( 119 Oxyquinoline 261 l)x)ieirac5cline )iydrccliloridc 3451 346— 347 Oxyrociii 845—846 Oxylocun injeclioii, 84iii 847 Osyiticin nasal soliiionc 846) Ocolinone, 615—616 6151 Paredrine Sec Flvdroxyaiiiplieiamiiiimc 41, b Paricalciiol 879 I,irl.tiisini's disease 574 l'arnaie Sec lr.iiis1cs puiiiiciiic sultaie Paroniiimycimi snlfaie 138— 339 338) Pariixeiine 518 Parsiilc,) Si'.' Ilihiiprcipaiine Imvdnic)iliir,ile Panial agonists, 48') Puma) salo) 755 Particle mesh isisuld nierh.id, 954 Partition coeliic.ent Il—It 181 tSr hailitgica) actis ity and Il 2) 181 191 Partiiiouiing phenoineita 18—19 Pasrenrieiiii,in 2181 Pailciton Set' Tridihese)IiyI c)ihiriiie Paion r.ite tlieoiy 572 Paiili exclusion lihiwiple 937 Pas'nliiim Set' Paiiciiiiniimiio Iironiide l'anil Sr-c Parimnemine Pasipaiii IIa)accpani P(' 17—21 181 Si I'('lls I pmily c)iliirinaied )iiptieiis Isp omeiabolusni a), 71 PCP Sec Plieiicyc)mdmiie ) Iiryihri.niyeimi etlmvlsiieciiiaie Pedianiycin Pedicn)icides 268 Pegaoiiime Sic- Iltliiiiiiin PegzLspargase 429, 43) -432 uidicaacnrs or 31)7 31)8 3091 nieclianisin ol acuon of 3lSli 3)11—3112 nonienc)aiiire or, 31)3 oral ahsorpiain uI, penict)linase—resistaiui 3)17 pniperiiesol 4119) prciieiim binding o),308 3)0)1 sci)uhi its or, 304 of aclivitv of 707 30% 309t siereuicheniis)rs of 303, 3031 siracrore ii 31)2i 11)31 ss nlhesis ii) 3)4 114), 1)161 voWs of 302— 303 I'emiiciUinase—icsisi.iai penicitliins 3)17 Ps'nici llina',es, Penicittiii (;, 4)19_i ))),3))9i Penicillin (1 ben,arhinc.3 Ii) Penicillin procaine.3 Ii) lis.iimcillmim N 3)8 3t9 Penicillin V.30) 311) Pennyrmiyal 9)5 Pciuaerviliril,iI iciranurame iii line,), 61St 627 Peniatuside 387 488 PenI.igasinn, 854 I'eiiiaiim 3i81 t'eni.cici,dine isei)iiiiiiaie Pemuianici)is-lnielaniine 429 Peniaimiidine (i68 262 t'cnianiidine t'cniaqiiine 288- 289 28'if I'enia,ocine 74)), 741 750-751 inciabolisni of 8)) 1.41 l'enihi ace S.', Nleth,isy)lurane I'enudi,,rhii,il nieiabcilisimi ii), SI Peiitiiliarhiral sinliunt, 4941 495 Pcnlcislaoi (i1' Sinlinni sltbi'glaconaie Peniosiutiii 4)18 313 liea)iiiftal Sicdiuni lliiuipenial s.nliuiii Peciinxil 5.',' Peciiaecvt)iiiiicl Ieiraiiiirale ,liliuied Peiits leiretctra,ote.5 lit l'en Vee Sec Penicillin V 5,-,- I aiitii)idine Peptarton cc l'eptic acid disease 718- 71') Pepric acol secre)iiin 718 71St Peptides csntihiiiatiirial ss iitliesis iii, 41, 441, 451 Pepxiids, conihinaioi xi) sy nlliesis 43—46 .151 62 I'erreot ioniiainni IS Percitdaii Osyctidone )iydrcichlarick Periuclin Sir (spriiliepladine Pegu.sy& Sit' Inierferini aba-Ia Perineurinni liS)) liMO) Peri1rliei xl iicrs iius sysleni 541) ),7i) I'egylated inierteriiim allu-2a, 18)1 1816 Pellagra, 89)1 89) Iieriirae.,S, Periiaemy ihritiil teiraiiuriile diluted Peniirolasi porassiuni ophilialinic soluiioim 16-7)7 Pernr.qx'ii Sit Peimit ilIum I beneathine 2-PAM pmdrug foriii ci) 157- 158, 1581 Pamaqiiine 288—289 2891 Penmtt)ine,514 Pumelor Sic Nortriptyline Panado Sic Aceiaminophen Pinion qciiiiqiii'Jinlini ginseng) 9)3 Puncreaiic hiiniioiies 847—854 Pancreaiiii, 838, 839i Pancrelipase 838 839i Penhriien See Anipicil)iic Pciuieilinn 21i8 Iieriiiiiil Sc Flmi1ihenaiine hs ilriich)oride Periiiciun,s nienoa 895 Peiibnumli.) 54 Pcrphenaeine 4991 5)8) p p53 391 PAIIA Sic p-Aitiinobenniic acid iPAHAi Paclitunel 425 427—428, 915 Pain, types of 73) Paiicreoeymin 854—855 Panvnroniiini bromide 593 Panmycin Ste Teiracyctiiie Paitietiti Sec Aliireiinoin Panteric See Pancreaiiii Paiiihen,iI 888 ¶441 Penciclovir 378 Peneirex See Entinacin Persanhne Sri Oipyridaiii,ile Penlliiriilii) 50) l'erionat 72 76)) l'ernur)saiani nieiltiids 93') I'enictllini s) 102— 11') acid resistance if, 3)19) acytnreids'-suhshiuied 308 allergy to 31)8- 7)83 bacterial resisiaimce to 1)15 31)7 $4aci.mm.ise inhibitors xsiltm.3 14—315 classificaiiim of, 3119, 1l)9i Paniopracote sctdcnin 722 7234 725—726 clciniliercia) prodntinni il 31)2—3)).) Puntoilienic acid 887 888 degrailatisni of 31)4 31)5 3)16) i)msci'sery and dese)cipineiii iii, 2403 exieni)ed-specinicii.3))7 - 3)18 l'apain $411 tic action iii, 837 8371 Peritifraice Sec l)esiliraniine )msdrutclc)oride Pesticides close nieiabolisini aiid 13) Pesi,in III 5,-c PET i piisiiroii emission ii'iiiogruphy I -156 4641 460) 4lilf I'rosiagl,niilinis PG syii)he)ase 8)9 POll $2)) P0)4 s5 iilliase 8)9 82)) 822 p1)1 82)) dcriratixes ii) 823 825 982 Index P-glycoproteins, in drug resistance 392 Phenylcarbinol 229 p11 Plsenylephrine, 532—533 calculation of, 13—14 vs percent ionizoion, IS plC,, and IS—lb 151 IS Phage vectors 165—166 1661 Phagocytosis 197—198, 19Sf 204—205 Pltagolyssssomes 197—198 1981 97 19Sf Pharmacogenomics 193 Pharmacognosy 905 Plsnrtnacological activity, statistical prediction of, 17—26 Pharmacological screening See Drug design; Screening Pharmacophore concept, in drug design 944 Phemerol chloride See Benzethonium chloride Phenacaine hydrochloride 694t Plsenacetin 761t, 762 active metaholites of 135t metabolism of 98, 116 Phenadoxone 739t Phenazocine, 740 Plsenazopyridine 253—254 metabolism of species differences tn 129 Phagosomes, 1291 Phenbenzamine, 704 7(15 Phencyclidine (PCP) 52(1 521 ntclabolivm of 82 psychosis due lo 497—498 Phcndintetrazine tartrate 514 Plsenelzine metabolism of 122 t23f Pheneleine sulfate, 515 51St Pltenergan See Piosoethazine hydrochloride Pheneridine 73ht, 737 Plsenetidine bIt 762 Plsenetsal 761t Phenlormin 668 Phenindamine tartrate 709—710 Pheniramine malease 708 Pttenimmines 707—710 Phenmetrazine, metabolism of 89 101 Phenobarbital 494 4945 as anticonvulsant 504 as ansiolytic/sedative-hypnolic 494, 494t drug intrmctions with, 131 as enzyme inducer 131 metabolism of, 70 Phenocoll 761t 762 Phenol(s), 217 221—223 corrosiveness of 14—IS glucuronidatiun of 115 liquefied 221 tnethylaiton of 12$— 126 2-Phenylethanol 229 Phenylethyl alcohol 229 fl-Phenylethytamine structttre—activity relationship for 530—531 5-Phenylhydantoin metabolism of 109 Phenylmercunc acetate 230 Phenylnsereuric nitrute 230 Phenyltnethanol 229 Phenylpropanolamine 538—539 Phenyl sallcylate 756 Phenytoin sodiunt, 505 5051 Pituitary gottadotropins 774—775 7741 Pituitary homsones 841—844 Pisalic acid pmtniety, 145 14Sf 13—14 14t, 1St acid/base strestgtlt and 14 drug distribution and 16—17 percent ionization and 15—16 1Sf lot pH adjustments aitd 15—16 1Sf lot values for 948t—956t as antianhythtnic 639-640 water volubility and 16 Placental barrier I' Placidyl Se,' Ethchlorvynol Planch quantans theory, 935—936 Plaquenil See as anticonvulsant 5(15 5(1St Plasmakinitss, 85(s—857 interaction of with isoniazid 124 metabolism of 70 124 132 133 species differences in l28 pHisol-lex See Heaachlorophene Phleomycins 417 Phosphate esters, as prodrugs 149 149f Phosphocol See Chromic phosphate P 32 Phesphodiestemse S inhibitors, active sites of 29 31)1 Plasmid vectors, 165—166 1661 Plo.smod/son ui-oh' 282, 283—285, 2841 Phu.srnor/iiuns spp., 282 283—285, 2841 drug action against 284—285 genisnte iii, 285 infection by 284—285 2841 Si',' rats,, Malaria life cycle of 2841 types of 283 Phospboinositol systesn 552 Phospltoline Iodide See Echothiophate iodide Phospholipase C 552 Pltosphoramide mustard 396 3961 Phsssphorothionatev 568 Phosphonts-30 457 Phosphorvlation Plassusodhum error 282 283—285, 2841 Platetetis) in DNA synthesis 154f 15Sf of ptsidmgs, 153—154 15Sf Photodynamic therapy for cancer 430 433 Photoelectric effect 936 Photofrin II See Portimer sodium Platinum consplexes 428 Platomycins 417 Plavix.S,'i' C'Iopsdogrel Plegine Si-c Phenditstetra.rine taflrate Plendsl.S,'e Felodipine Plicamycin 414, 417, 424 Pluripotestt stein cells 177, 17Sf 197 19Sf PM3 method, 938 Pneumocanadins, 246 Pneumococcal vaccine, 215 Plsysostigmine, 563—SM 563t 5641 Physostigmine salicylate, 564 Physostigmine sulfate, 564 Phytoesteogens 778—779 77sf Phytonadione 884—885 mettadlisne conversion to S Picrotoxin 510 Pilocarpine hydrochloride SoIl Pilocarpine nitrate 56(1 Pimaricin 237—238 Pitninodine, 736t 737 Pimoride 501 Pindolol, 543, 544f Pink disease 891 Pinocytosis S fibrinogen receptors 'itt, 633—634 functioits of, 665—666 Platelet aggregation 665—667 csobf inhibitors of 666—667 Platinssl See Cisplatin P,ieuunou'sstis ,'ocunhi, 264) Podophyllotissin, 424 Polaratnine.S,'e Dexchlorphetiirasnine malcats' Polani'alissn functissns, 938 Pisling algoritltists, 933 Polio vaccine, 2111, 212t Polyacrylamide resins, in costsbinatorial chemistry 49 Potychlorinated biphenyls (PClls), metaholisas of 71 Phentermine hydrochloride 513 Phentennine ion-exchange resin 513 Pins, in combinatorial synthesis 44 4Sf 62 Pinworm infestation.s 265 Pioglitazone 672 Pipanol See Triheayphenidyl hydrochloride Pipecurittm bromide 593 Piperacillin See rats' i Penicillims spectrunt of activity of, 31)8 Piperacillin sodium 309t 314 Piperacillin-tazoboctam 316 Piperazine estrone sulfate 780 structure of, 777f Piperazinelsl 265 706—71)7 706f Piperocaine hydrochloride 690—693 69lt Piprucil See Piperucillin sodium Piranthicin 416 Pirbuterol 536 Piretanide 61 If Piritresim 410—411 Phentolamine 539 Piroxantrone 429—43(1 Phenylalanine hydrogen-suppresved 23—24 Piroxicant 760 Pitocin See Oxytocin injection Pitressin See Vasopressin injection 49 Polythia.cide 605—(sltt, (Slot, bUst 620 Pondimin See Fenflurastsine hydnw(tlondr Ponstel Sri' Mefestatnic acid Porfimer sodtusn 43tI 433 Pitressin Tannate See Vasopressin tannate Porliromycin 419 Pituitary antidiuretic hormone See Vasopressin Porlamines, 533t topical 234—235 Phenol coefficient 221 Pltenntlsiazines anlihistansine 7111—711 antipsychotic 498—500 499t metabolism of 87 ring analogues of, 499 Phenoayacetic acids 613—615 Phenoxybenzamine 540 Pttenonymethylpcsticillin 310 See ratio Penicillin(s) Plsensusimide 505—506 metabolisttt of ICY.) Phenteemine metabolisnt of 91—93 24f 24t 25t Phenylbutazone 762 763t active melabolite.s of t34 135t metabolism of 70 82 114 Polycillin See Ampicillin Polycyclic aromatic hydrocarlxsns carcinogesticity "I, 74 74f Polyene antibiotics iS—238 Polyethylene glycol in combinatorial chemistry, 49, 62 Polymerasc chain reactiost in combinatorial chemistry S2 62 Polymer heads, in combinatorial chesnistry, 48—49, 6(1 Polymos See Amoxicilliu Polymysin B sulfate, 357—359 Polymyvins 3(Xlt 357—358 Polypeptide antihiistics 355—36(1 Polysaccharide-coated superparaniagnetic trots "side particles (SPIOsI 477 Polystyrene resitis in coinbinatisrial Indev Procainamide hydrochloride 638 Pocaconawle 244 Posicor See Mibefradil Procatne 678 Positional cloning 167, 167t losiuonal scanning 51, 62—63 Positive inotropic agents 655—657 Positron emission 456 Positron emission tomography d'ETI 456 460 .1601 4611 contraceptives, 794—795 Potassium channel openers 654—655 Potassium ion channels 681—683,6)121 See also Ion channels Potassium leak channels, 681 Potassium sorbale 230 Potassium-sparing diuretics 616—618 6161 preparations of 620 Pswidone-iodine 223 Poxs'i,uses 3701, 372 Pradimycins 246 Pralidoxime chloride, 571 Ptatnoxine hydrochloride 694t Fl'jndin See Repaglinide Pranral See Diphcmanil methylsulfate Petsachol See Pruva.statin Petsastutin 663 Ptaarpam 491 Praziqnanlel 267 Ptazosin 540—541, 541t 652 metabolism of, 98 109 Preccf See Ceforanide Precipitation 175 PSecose See Acarbose Ptednicarbate, 81)111, 813 PSednisolone 811 metabolism of I 10 relative activity oF 8091 ioluhility of, 770t structure of, 807f Ptminisolone NaPO4 salt solubility of 7701 P(ednisone 1111 active nietabolites of, I 35t as antineoplastic 435 relative activity of, 81)91 Pregnancy hCO in 775 placental bamer in Pregnenolone in steroid biosynthesis 768 769, 7691 Estrogen(s) Premphase See Hotmone replacement therapy Prempro See Honnonc replacement therapy Preservatives 228—231) P(rvacid See Lancoprazolc Priltacaine hydrochloride 690—693 6921 Ptinucor See Milrinone Pemaqaitie 288—289 2891 295, Fhnuiy pulmonary hypertension 823—825 Piintasin See lmipcnent.cilastin Plimidone 506 active metabolitcs of, Prnchlorpcra,.ine malcntc, 4991 5(X) Procrit See F.poelin thu Procyclidine hydrochloride 583—584 Prodilidine 737,, 738 Prodrugs 109 142—159 activation of 142—144 152 by azo cleavage 149—ISO IS It' chemical, 155 1561 by oxidation 152 by phosphorylution 153—154, 15Sf by reduction 152—153 1531 advantages oF, 142, 154—155 alcohol promoicty for 144—149 145f—l491 amine, 149, 1501 azo linkage and 149—150 1511 binprecursor 142 143 152—155 in cancer chemotherapy 156 carbonyl pronsoieties for 150—152 l5lf cartroxylic acid promoiety for 144—149, 14Sf— 1491 earner-linked 142—143 145—152 as chemical delivery syslents 155—159 1571'— 1591 definition of, 65 142 in immune response 205 Premarin Sue Procaine hydrochloride, 690-693 (,9lt Procan SR See Procainamide hydrochloride Procarbazine hydrochloride, 397, 402 Procardia See Niledipine 35, Principal cclii, of ncphron (rOll Principal components analysis 511 63 Ptincipen See Ampicillin Ptinivil See Lisittopril P,i.scoline See Tolnzoline Psistinamycins 363 Ptisine See Naphazoline ProAntaline See Midodrine Pto'Banthine Sri' Propantheline bromide Plirbenecid metabolism of, 70—71 Probucol 662 Plocainamide 638 active metabolites of 135, metabolism of, Ill), 122 124 double-ester, 146—147 14Sf drag distribution and 4—6 ester 144—149 1451— 1491 of functional groups 144—152 hydrolysis of 146—149 Manniclr bases and, 149 1501 metabolism of 142 146—149 mutual, 142—143 prornoieties and 142 solubility of 142 145 147—149 For unpalatable parent drugs 145—146 Productive infection, 367 Product stereoselectivity 103 132—133 Proencymes 837 Progestasert IUF) Si'e Progesterone IL'D Progesterone as antineoplastic, 434 biological activity of 785—786 786, biosynthesis of 769 7691' 785 formulations of, 788 metabolism of, 785 7861 structure of, 71171 Progesterone (UD 793t 794 Progesterone receptors 773 Progestins, 785—789 as antineophistics 434 biological activity of 785—786, 786t biosynthcsts of, 769 7691, 785 in contraceptives 779 790—794 7911—793 endogenou.s 785 itt honnone replacement therapy 796—797 7961 7971 metabolism of, 785, 7861' products 787 progextational activity of, 786 786t structural classes of, 786 7871 synthetic 786 therapeutic uses ttf 787 Proguanil and atovaquone 29lf 292 292f ProHance See Gadotendol Prohcptazine 738 Proinsulin ((47, 848f See also Insulin, recombinant Prolactitt 844 98.3 chorionic growth.hormone 845 metabolism of Ill Prolurtin—releasing hormone, 841 Proleukin See Aldesleukin Prolixin Fluphenazine hydrochloride Promazine 498, 4991 Pronicihazine hydrochlortde 710—711 Prometrium Progesterone Promoietics prodnig 142 Promoters 168 Prompt insulin zinc injection 1(5 It Pronestyl See Procainamide hydrochloride Pro,tethalal 542 Prontosil 149 1511 269 Propacil See Propylthiourncil Propadrine See Phenylpropanolamine PropaFenone 64(1—641 2.Propanol active metabolites of 220 Propantheline bromide 582 Pruparacaine hydrochloride 690—693 691, Propecia See Elnasteride Properidine, 7361 Propine See Dipivefrin Propionic acid 233 Propofol 488 Propoxycaine hydrochloride 690—693 691, Propoxyphene 738 7391 metabolism of, 85 Prxtpoxyphene hydrochloride 749 Propoxyphene nupsylate 749—750 Propranolol, 542—543 active metabolites of 135t metabolism oF 70 89, 103, 112—114 114 Propylamines, 707—7 10 7(171 Propylhexedrine 5311 Propyliodone 484 Propylparnbcn 229 Propyl p.hydioxybcnroate 229 Propylthiour.tcil, 674 metabolism of 114 126 Proscar See Finastende ProscWOS See Phenyl salicylate Prustucyclin.slerived drugs, design and development of 823—825 824t—825t Prostaglandin(s) 666—667 See also Eicosanoid(s) antiulcer 726 biological activity of, 822t biosynthesis of, 18—822 8191 8201 in coagulation 666—667 discovery and development 01' 818 8I9f 820f metabolism of, 82 If 822 Pl'ostaglandin unalogues design and development oF 823—825, 824t—825t invesligational 824:—825, ophthalmic 823 828 Prostuglandin 01 1(221 Prostaglandin E1 822t 827 Prostaglandin E1 cyclodextrin 827 Prostaglandin 8221 827 as abotlifacient, 795, 7951 Prostaglandin F1, 822t Prostaglandin F1,, 827 as abortifacient, 795 7951 Prostuglandin H2 820 Prostaglundin 820 8221 Prostaglandin inhibitors 754 Prostaglnndin J1 822, Prostunoid receptors 825—827, l126t Prostanoids for vetennary use 828—829 Prostaphilo See Otiacillin sodium ProstaScint Kit See Capromub pcndetide Prostat See Metronidazole 984 len!,'.; I'rostate cancer anliandrt.gens lot 801—802 8021 estrocens for 779 l'room E2 S ' l'r.istaglan.Itn F Poisiji, P2 Alpha Sec Proslaglandin p:, l'rostin VR l'ediat it l't.isiagl,.n,lin I., Pr,.taniines, 833; Protat,,tne suII;ite, 667 I'rotaintne tune tisnlji, suspensuin sS tt 852 852t Protease catalysis 837 8371 Protease inl,ubn,,ts anti-I 11%' 184 —l$7 I'rotruptyline hydrochloride .S 17 I'r.itropin S Si'ntatretu Priveinil Set- Alhuier,,l Pnn-era S,, Medr.rxyprogesterone acetate in snhstitueni selection, 22—23 23t threeitiunensior,aI 21.18—19 Quadrainet Samarium SM 53 lex,dronarn Qua,,titatise sun.ett.re—acov.ty relaliu'nship I'rorigil S.c M.nlaftnil IQSARI hl—21 See of." QSAR l'n't itanot, A 869—87)) Pri's itanuitr I) 875 studies Quauuintui dots, 53 l'r.',ac See Ilt.oxettue Qt,.,titt.ni ,neehaut,es 38 923 in compttter-assisled drug design 935-939 Quarean Ctidittinuo bromide l'seu.d chuoltnesteru.'.e 564)- 56), 5611 4- ).Psett.Ioepltedriiie 538 Psead,.n,,.n.,I i,ttect,,,ns air.tut gtyc snte-rrsisiat.I 336 ceplralosporins ti'r 325 326t fl tactain-resisiant 32.1 Pseu,t,t,rumtc acid A 362—363 Qua.eeparo 492 Questran Si-c Clu.lesuyrannne resin Quetiapune 5112—51)3 h'seudouropune 575 Qninacrine hydroct,I,,ride, 293) 294 Quinagtute Se,' Qt.unidine gluconate Quhrtapril 646 647) 6471 acute phase 2))) 21W Ps,l,win, 521 Quinelhartine, 6(17—6)0 1,4171 Ôtt9t, 62(1 apgn,gati,.,u il 175 Psilocyhiti 52) Psyctt ses 496 498 t'nturrcort t,.rh,,l.alcr See Budeso,,ide Qitinidine 286, 286) 287 295t active ,,tetabol.tes ,ut I 1St tttetab.,I,sm ol , 77 Quit,i,Iine gluconate 638 Qainidine 638 ileuel.'pment iii 942 9431 ant.neoplasuic 446—447 Protein), I S ,l,,' Recepi''ris itnpholeric behavior itt 833 of 173 174$ Iiltkitl 857 858 buried 833 cheunislr) of 173-175 1711 chimenc 168-169 in dote screening 172 c nkirmatn.n ii 831 —832 8321 815 doug—receptor iutteraclii,ns ''itt 28 conjugated 833 deanodat,on of 173 I 74) denatnr,,Iuon Of 173- 175 833 tirceulation ol 175 fusion, 11.8—11.9 in Intg screening 172 hydn.lysis 4,1 173 17.11 hydrophobic Force' ii 831 instability 'I chemical 17 1711 physical 171 175 oxidat il 171 1741 piattranslational nh,nJiI ieali,,uis iii 162—Il,) 1631 precipilar.u'n ot 175 products 814-835 properties of 833 pnriticatu't 4,1 833 race.,uaauiou 171 741 reco.nb,na,ti 11.8— 169 immun gen.city.uI 175 separation and ideu,tilicati,', itt 814 simple liruel 811 $33 813t soluhility $33 $13t structure of 162 71 811-833 $IIL 8121 ,Iatahasec iii 39- 41) Factors alfrct.ng 832—833 surface adsu'rpti.'n itt 175 synthesis ot 62 63 1631 Protein I',,, if.ed c.un.c tr pun Sir Reposit.'ry ctirttcotropin injection l'urine nucleotides the n,,v,, synthesis of 4)12 -4184, 41)3) —41841 1133 classiticutu.'n color lesus 1w 834 Protein binding I Protein C 665 883 Protein c.'y.nes S,' h',,h,r,,,,,arv hypertension 823—825 ne See Dontase alla P,,,iu,etltol S.',' l.—Nlercapl lrarine l'Vi'-sutir,e St I',.s I'r.tli.I.'xi.,te chl.'nde I'r tu.porphvrin IX it cvtoclrrotne I'—451l 67 Protriplyline inetabolistu ol 76 Prurroparn chloride Qninu.lumes, 247 -252 properties of 247 -248 2491 types iii 248 -252 Q.nnoplrenol 261 Qu,unosol 5,'.- I'> taa,,tid,,re 7t.2 t'yrae.il.ihuned.nne der,v,,tives 762— 763, 7(.3t K i'sran'lit,e 762 Psran.l.,,,e ,teiivaiives 762 ibe.t,ar.,ine citrate 705 l'yr.tttne ninhrydrin lest for $34 I'y odi.,n; Ste l'hetuan.pyri.litte Pvrid.'stiguuine bromide 5631 565 Pyridt'x t 89) Pyridoxal 5plt sphrate, 892 —894 i.l xan,ine $91 Pvrid xine $91 —894 deliciency oh 8')) dietary s,iuree.s of $92 drscosen il, 89) h,,,ntones ti,,), 893 -894 Qninnpristin-daItoprrsuin 363 QVAR i' I(eclotrrethas,.ne diprurpionate Rahepra.eole sodit,n,, 722 723r 726 Kacemic catciutni panrotl.enate $88 Kacemic mintnres ntetatb.'tisnt of t 32 Raeenti,ati,.u protein 171 1741 Racem,.ran,idr 738 719, R:icetruorphan 738—719, 75(1 Radanil.S.'e Ben,nida,,.le Radiati,.n 454- 458 atuttittitati,.t, 456 hiologucal etlects ut 457—458 delinitiurn of, $54 direct effect utI $57 ehectrounitgnet.c $54 indirect ellect of 457 ionieing 454, $51 properties of 454—451 .uI, 89) —$94 t'vrud xine hydrochloride 894 Pyndost'l 892 P5 rilanuine ,i,aleate 7115 I'yrunrethanrine, 27) I'ynrnetltamine'snlfaduaeune 271tt 2891—2911 2911—292 291,1 I'yr.n.idtne urncleosi,le antagonists 40$ 41191 l'yr''nil 5.' Pyrrobutantine phosphate P/i insulin %51t, 852, 852t r.idioactive utecay intl 455 -$57 Radiati,,,, ,thsorbed dose $57 Radiation dosu,netr 457 Radi,,activr decay 455—457 Radiotrequency enciuding 53 Radi.'gntphy 472 -473 Kadioh gic pru.cedures 478—481 cintirast agetits tiir 472—484 Radiu.pharmaceutieals radiotraeers For 458—472 Radionuettdes $55 457—462 Se,' olin Radnuphtaritraceuuueals daughuter 455 sates 8311—831 Protein kinases in tnnt.'r.geuesis .138 Protein S 883 Protein tyrosine Ltnase iulrit',uns 438—441) Prote.rnties 193 in dn.g developnreni 44') I'r.rthronrhin, 663 664 664t 64,41 665 I'r,,tonix c i'anropra.'ote sodit,rrt Proton pump inhibitors 722—726 7231— 725) 721i activnt,.urt ol 155 1561 Quinine 286-287 2561, 295t Py.'pen S,, C'.irtrenicilhiu, ilis t.uitr t''.r.ii.tel patit.xtte, 265 I'yr 'inamtde 254, 255 256 l'yraeinecarbosamide S.- h'yra,inatnide l'yraioles 762 Ps rrob,tla,nine phosphate 741') tries Qatnidmne salIate 637—638 Q QSAK studies, 17-23 bilinear tumId in 21 - 22 2)1 lis-e-di,ne,,sional 23 tHur—,lintensi na), 21 tdentitv variables in, 23 linear trunlel in 21 -22 211 ',,ieut,,,tlwater system in 19 lIt parent 455 production itt 461—462 pttiperties 454—456 Irttnsf,,rnratiuin itt $55 —-157 Radninuchide test kits monochonat antitnnty 190-191 Radii.phartnacettuieals 454—484 contrasi aget.ts 472 —$84 See ,ti,o C,,utrusu agents parabolic model in, 21—22 2)1 pantiton coeltic,ent un I 9—21 pltysicochemucat par.mreters in 21 211 t)u.'ritte 468 gallium 468 predtciive pln.rniacoptu.ne u.a.utels and 944 iodine, 468-469 indium, 469- •171 moituclonal atttih'tdies 47)) Reconthisas 186, 86(lt radiotracers 458—472 leehnetittm 462—41,7 So-Rednctase inhibitors, 802—803, 81)31 thalliam, 472 venus 472 Radiotherapentic agent' 444—445 Radi,.qruccrs, 458—472.3?,' a/xe Radiophanoacenticals Raloxifene 7811 782 783 actutttts uK 29 Ramipril 6471 6$7t 648 Randottt screening I Ranüidine 7391 72)), 720t 721 —722 RAREs 872 Lit protein 438—439 Ratio 1.5 contntst agents 473 Ratio contrast agems 473 Rational dntg design 1—2 919 92)) 940 Set' talc,, Drug design Randisitt ci Rattwolita RanSed See Kcserpinr Ratiserpal See Ranivitllia Rausal See Rauscolita Ransst,Ilia 650 Rutot'oif,o si'ep.'ittiiio 651) Rayderm See I'henyl salicvlatc rDNA technology 163- 194 858- 86)1 859t S i' also IIiotecltnolttgy in receptor isolatiott 28 step' in 858—864) Rehutsetinc 519 Receptoos) 8—9 27—29 Sit a/s.' specific t)714'.s allinity 1,tr a.syntuttetry "I 35—37 chiuneric 169 1691 clotting of 28 172.S.'.' ia/so Cloning distribution of 28—29 drug ltindittg by 27—28 virtual screening for, 55 drug interaclions with Ste Drug—receptor ttderacttons flesible 28 as lutactional areas 28 heterttgcnetty ol, 169- 171) 17))t isolation of 28 ttteittbratte-hotttid isttlation al, 28 t,r.etttation of, 28 properties iii, 27—29 specificity of 28 structure ttf, databases of 39—40 variability itt 28—29 Receptor-baseti drug design 55 939944 Receptor '.election and antplification technology lr-SAT assay 171 Receptor tyrosiute kinase inltihitors 438—44)) Recottthinant DNA wcltttolttgy 163—194 858—864) 85')t Ste a/si Biotechnology DNA processing in 172, 860 DNA production in 364 166-168 860 in receptor tsolatiott 2$ steps in, 858- 861) Recombinant drag prodttcls, 859t—sotlt 864)—863.Sre ,,lso Biotechnology ond u/ie.'tfic prts/zat-cs ADME propeoies ol 175 hioasailahthity ii), 175 drug delivery ot, 175 tttctabohism of, 375 types of 175—191 Recounhittatti proteitts 168 — 69 Se,' ,,ts,' Ilio(echnology immnnogentcity of 175 pruwes.sittg of 172 Recotnhinate Set' Factor VIII, recotohittant Redaction, tn biotransformation See I)rug metabolism, reduction in Redun See I)esfcnfinratmine Regional nerve blocks 687.5ev ia/ut Local anesthetics Rcgioselectivity itt drug ntetnbohistn 133—134 Regitine See Phentolamine Regranea Gel See Becaplerntin Regular insttlin 853 85 It 852t Relalen See Nahumetone Remeron See Mirtantpine Remicade See Inilisintab Retttifetttunil hydrochlonde 748—749 Reminyl See (lalantumine Retnodulm See Trepro'attnil Remosipride 502 Renal drug eacte)itttt, 41 Renal Failure, drug metabolites in 134 Renal solute reabsorption 596—601 5971—6001 See also Nephotn Renal tonielty nI sulfonantides 122 274 Renese See Polydtiazide system, in blooni pressure regulation, 642—645, 6431—6451 Renin•angiotensin system inhibitors 645—646 6461 RmuPru' See Ahcisltnah Repagltnide 671 Replicons, 165 Reporter genes, in drug screening 171-172 Repository corticotropin injection 842 842t Rescinnamine 529 Rescriptor See Delavirdine Rescula See Unoprostone Reserpitte 529 65)) 6501 Reserpoid See Reaerpine Resitts in cotnhinatorial synthesis 48—49, 481 63 Rcsorcinol 222 233—234 Resiasist See Ferrisan Respiratory hurst 203 Resting potential, 68)1 Restoril Temazepam Restriction endonucleases 164—165 16Sf lost 860 Retepla.s'e 184, l84t Retevase See Retepha.se Reticaloendothelial system 198—200 199t Rettn-A See Tretinoin Retina, vitamin A and 871—872 872 8721 Retinal, biosynthesis of 879 Retinoic acid, 867 870 biological activities ntf, 872 Re Via See Nahtreat,tte Resitlate See Snuliunt tltto.sahicylate Rhtnocort See Bttdesonide Rhodutpsin 871 872 872f Rhythttttd.Se.' Potpafettone Rihavirin 381—382 Riboflavttt, 89(1—891 Rchard.san approach 922 Rtt'abutin 257 258 Rifadin Set' Rifatttpin Rifantpicin See Riltmpin Rilampin 254 257-258 300t Rifamycins 257—258 Rintactane Ste Rtfampin Rimantadine, 372 373 Riuttemtlotte lIt, MIII 833 Ring equivalents 43 Ringwornt 23)1 233 231t 233—235 R istitner 35—36, 371 Risperdal See Rispcridotte Risperidtttm 497, 501 Ritalin See Methylphenidate Ritodrine 537 Ritonavir 385—387 942 Ritsert 678 Ritasan See Ritusimab Ritusimab 389 443 444 Riva.stiguttine 567 RNA 362 anttscnse 393— tM modeling of 92(1 RNA viruses 368t 369t, 371 —372 Rithasin See Methocarbanttl Robinul See Glycopyrrolate Rocephin St', Ceftriasone disodium Rocttagan Set' Bettznidantlc Rods and cones 873 872 Rofecttsib, 760 822—823 Roferon A.Se.' Interferon ahla'2a Rohitetoucycline.345t 346 as po.drug 149 151)1 R,atnilar See l)csurotttetltorpltan ltydrthrotti Rondotoycin See Mcthacychinc hydrochlori Ropivacainc hydrocltloride 69(1—693 692) Rose oil, 229 Rosighitazone 673-672 Rotasirus vaccine 213 Rotrecctgitt alfa 185 Rttandwortn infestations, 265 Rtuaiam Set' Rcmosiprude r-SAT assay 171—172 RU-486 See Mifepristu'ne Rubella vaccine 214) 212t Ruhidomycin See Daunombicin Rule of Ose Lipinsku 40 55 62 Rynatass See Carttetapentatte citrate unetahohism atE, 1)69 Retinoic acid receptttrs 872 Retinttids, See a/so Vitamin A antineoplastic activity of 430 delinition of 868 Retinoud X receptors 872 Retinol, 868 See u/to Vitamin A absorption of 869 esterilication of 869 unetabolism of 869 all-teana-Retinol 867 KitE biosynthesis of 872 8721 Rerinol-binding protein 869 Retroviruses 371 —372 380 Reverse tr.mscripta.se inhibitors, 372, 379—38) nt,nnucleostde, 383—384 resistance to 382 Reverse truutscription 371 -372 380 Reves See Nalmelene Itydrocltloride S 5-145, 824t Safety—catclt ltnkcrs un conthinauttrial synthesis 49 63 Sairole tnetabolisnt itt 80-SI Saint John's won 908—910 Salbutamol tnetabolism of, 87 115 Salcto See Salicylanutde Salicylatttide 756 Salicylanilide 764) 76lt Salicylic acid, 233—2.4 754 ntctalxtlisnt of 114, 117 Sahicylic acid derivatives, 754 —757 Salk vaccine 211) 2l2t Salnieterol 536 Salol principle 755-756 Salsalate 757 Saltatory cttndactiu,n 680 986 hider Suluron Sec Hydrotlumethiazide Samarium SM 153 lexidronam 444 445 Sandostatin See Octreotide acetate Serum globulins, 857 Serzone See Net'arodone Sevotlurane 486 Sandril Sec Res.erpinc Saniti,aiton I St Saquinuvir, 384 development of 942 943f Sargramosttm 179 430 432—433 859t, 863 Sex differences, in drug metabolism 129—13(1 Sex hormones, 775—7119.5cc also Steroid(s) biosyttlhesis of 768—770, 769f 775 in chemical contraceptives, 7$9—795 See SAR with NMR SI Sawmomab pendetide 191 859t progestins 785—789 Sex steroids biosynthesis of 768—770 7691 Sibutramtne, 514 Sickling disease, malaria and 283 Side effects, Sauvagine, $35 Saw palmetto $03 Sanitoxin, 690 Scahenc See Lindane Scabicides 26$ SCF method 93$ SCH 59884 244 Schizophrenia, 496—498 aLso Contraceptives Signal transduction inhibitors, 438—440 Sildenafil active sites of, 29 30f Silvadene See Silver sulfadiazine Silver sulfadiazmne 279 See also Sulfonamides indications for, 2701 uiprodrugs 142 145, 147—149 water and, 16 Soluble suppotts 49 63 tagging of, 53, 61 Solute, renal reabsorption of 596—601 597f -6001 Solation.pltasc coinhmnatorial chemistry, 49, 5111 Suls'ation models, 934 Ssmlvent.acccssible surfaces, 922 Solvents, in molecular dynatnics simulations 934 Soma Sic Carisuprodul Somatic cells trunsgenes in 94 Somatic nerves, 54$ Somatoliberin 841 Somatostutin 841 845 Somatotrupin $44 Schraden, 570—571 Schrodinger wave equation 936—937 Silvbum marianum (milk thistle) 914 Similarity probes 56 57t Sotnatotropin release—inhibiting lactor (SRIF( Schwann cell, 679 6791 Scintigraphy 458—460 4581 4591 Scintillation camera 458—460 4581 4591 Simple proteIns 831 Somatrem Ill, 844 %59t Somatropin for injection, 844, (1591 Sonata See Zaleplon Sorbic acid 230 Scintillation proximity assay, in highthroughput screening 54 541 Scopolamine, 574 577—578 Scopolamine hydrobromide 578 Screening Sec tal.w Computer-assisted drug design of antineoplastic agents 392—394 3931 automated I biotechnology in 170—172 1731 heterologous expression and 17(1—172 1701 high-throughput 26—27, 40 401 43, 53—54 541 944 human-tumor.colony_forming assay for 394 madam 1—2 reporter genes in 171—172 virtual (in silica) 54—55, 56, 419 919 senogralt models for 394 Scurvy, 898 Search query, database, 56 Sehatrol Sec Flutamide Secobarbital metabolism of 76 77, SI Secobarbital sodium 494t 495 Scconal See Secobarbital sodium Secondary mass spectrumetry 52 Second messengers 171, 172, 552 Secretin 854 Sectral Si's' Acebutolot Sedatives See Anttiolytics hypnotics, and sedatives Seizures 503—504 Seldane See Terfenadine Selective estrogeti receptor modulators (SERMs) 28—29 291 781—782 7811 agonistlantagonisl nctions of 29 Selective scrotonin reuptake inhibitors 18—520 Selective toxicity 217 Self consistent field (SCF) method 938 Self-renewal, 177 Semilente insulin 851t, 852, 8521 Sempres See Acrivasune Senapax Chimeric See Daclizumab Sernx See Oxazepam Serentil See Mesoridazine besylate Serevent Sec Salmeterol Scromycin See Cycloserine Seroquel See Quetiapine Serosal immunity 200 Serpasil See Reserpine Serpins 665 Sertniline 519 Serum 857 Simvastatin 663 Sinequan See Doxepin hydrochloride Single photon emission computed tomography 458—460 4601 S isomer 35—36 371 Sisomicin sulfate 341 $.Sitosterol 661 Skin infections, fungal 231, 23lt topical agents for 233—235 Slater determinant 937 Slater type functions, 937 Sleeping sickness, 26(1 Sleep-promoting agents 488 Slow-reacting substances of anaphylaxis (SSRAs), 820 Smallpox vaccine, 21)9 Smoking, drug metabolism and, 131 Snake vcnoms, 835 Sodium, renal reabsorption of, 5961—6001 597—601 Sodium 4-aminosaticylate, 256—257 Sodium antimony gluconate 263—264 Sodium uscorbate 899 Sodium benzoatc, 229 Sodium caprylate 233 Sodium equilenin sulfate, structure of 777f Sodium estrone sulfate, structure oF, 7771 Sodium iodide 1131,444,445 Sodium iodine capsules, 469 Sodium iodine oral sotutionlcapsulc 469 Sodium ion channels 681, 682—683 6821 5cr also Ion channels Sodium nitrite See Nitrovasodilators Sodium nitroprusside, 654 Sodium PAS 256—257 Sodium phosphate P 32 444 445 Sodium-potassium pump 682—683, 6821 Sodium prupissnate 229 Sodium salicylate, 755 Sodium stihogluconate 263—264 Sodium Sulamyd See Sulfacetamide sodiunt Sodium sultacetatnide indications for 270t Sodium thiosalicylate 755 Soft drugs 142 Solanacca spp., 910 Solanaceous alkaloids and analogues 574—579 Soletene Sri' Solid.phase synthesis, combinatorial 46—49 46f Solid supports 49 63 tagging of, 52—53 521 52t 61 Solubility lipid S and 17 $45 Sorbitrate Sec Isosorbide dinitrate dilated Sonatane See Acitretin Sotalol, 543 5441, 642 South American sleeping sickness 260 Sparfioxacin 248, 252 Sparine Sec Proma.sine Spatial amlys microchip, in combinatorial synthesis 44 4Sf 62 Spatially addressable synthesis 27 Species differences, in drug ntetabulism 128—129 Specific immune globulin, 21)7 SPEC'F (single photon emission computed tomogniphy 458-460, 4601 Sprctazole See Econazole nitrate Spectinomycin 335, 341 Spectrobid See Bacamptcilltn Spectrophotometry, in combinatorial cbeitiisu SI Spermatogenesis regulation iii 774 7741 Spinal anesthesia 687 See alum Local anesthetics Spints 219 Spironol;mctone 6l6—6t7 6161, 6211 815 extrurenal activity of 619 Spirunolactonc.hydrochtorothiazide, 620 Split-and-mix synthesis, 43, 44f 62 Split-level basis sets 938 Sporanox See Itraconazole SQ.29548 8241 Squalene cpoxidasc 238—239 2391 SRSAs 820 Stodol See Butorphanol lartrate Stanozolol 7991 801 Staphcilhin Si's' Methicillin sodium Starlix See Nateglinide StAR protein, 768 Stathmokincsis, 427 Statistical methods, in drug design Staurosporlne 438 17—26 Stavudine 381 Steepest descent approach 930 Stem cells, 177 1781 197 l98f Stereochemistry of drug metabolism 132—134 of drug—recepror interactIons, 31—34 Stcreoisomeis biological activity of 35—37 351 361 Stereoselectivity 35 103 product 132—133 substrate, 132 index Stcnlants, 218—223 218! classification of, 218 21%t elicetivenecs of evaluation of 219 improper use cr1, 219 phenol cnelficient for 221 Sterile capreomycin sulfate 259 Stenk carticotropin '.rnc ltydrcmide suspension Succinate esters, as prodrugs 147—149, 1491 Succirtimides 505—51)6 metabolism of 109 Succinylclioline chloride 593—595 Sucorrtrin See Succinylcholine chloride Sucralfate 726—727 Sudafed Set' L.( l-Pseudoephcdrine formulations of 275—279 half-life of, 276t indications for 269 2701 for intestittal disorders 279 isonizatlon of, 272—274 mechanism of action of 270—271 271 f—273f androgens 797—803 Sufentunil citrate, 749 Sulur See Nisoldipine Salbactam 315 316 Sulbactam.amprcillin 316 Sulconazole nitrate 242 Sulfacetamide 276 Sec also Sulfonamides Sallacetumide sodium 278 See also Sulfonamides metabolism of 122 1231 269 274—275 microbial resistance to, 275 mixed 277—278 nomenclature for 269 2711' nonahsorbable 278—279 nonalanine 269 oral 269 values for 269—270 274 274t us angiogenesis (ultibitors 447 biosynesis of 768—770 7691 Sulfachloropyridaz.ine 276, See al.crt Sulfonamides contraCeptives 789—797 endogenous cofliCosteroidc 81)3—815 estrogen 775 —785 Sulfadiazine, 276t 277 See also Sulfonamides Sulfadiusine sodium 277 See also Sulfonamides Sulfadoxino 276t prodrug forms of 269 279 protein binding of 274 275 side effects of, 275 spectrum of action of 271 —272 structure—activity relationships for 275 structure of 271f 842—843 842t Stcrilc sasopressin tannate oil suspension 846t 847 Steriliration, 2181 Steroid(s) 767—815 adrenal 803—815 onabolic androgenic See Androgen(s) metabolism of 106 114 nomenclature for 767—768, 767f 7681 numbering of 767 7671 overview of, 767—76* pharmacokinetics of modifications of 770 77 If proctrug forms of 158, 1591 770 7711 piugestins 785—789 properties of 770 770t solubility of 770 770t stereochemistry of 767—768 7671 7681 Stemidal estrogens, 776 7771—7781 Steroid hormones pyridoxinc and 893—894 Stemidogenic acute regulator)' (StAR1 protein, 768 Steroid receptor complexes structure of 773 Steroid receptors, 77(1—773 7721 structure of 772 7721 types of, 773 Stilbenc metabolism of 77 Stimate See Devmopressin acetate Stimulants, 510—522 Stochastic simulations, 935 Stomach See under Gastrointestinal Stovaine See Ainylocaine Small See Idoxundine STP metabolism of 91 Strain differences, in drug metabolism 128— 129 Stniub reaction 735 Srreprase Sce Streptokinnue Sueptokinase 839—840 Streptomycin cntltubcrculous activity of, 254 discovery of 299 334—335 Saeptomycin sulfate 337—338 Slreptonivicin 361—362 Streplorocin 420 424 Strontium 89 chloride 444 445 Structure—actisity relationship 19—23 38—39 See also QSAR studies and cpeeiJk drugs indk—.itions for 2701 Sulfudoxine.pyritttedtamine 277—278, 2891—29 If, 290—292 296t Set' also Sulfonamides Sulfalene indications for 2701 Sulfometbazinc, 271f 276 See n/co Sulfonamides metabolism of 122 1231 also Sulfamethizole 275—276 276t Sulfonamides Sulfumetltoxazole 276t 277, Sec also Sulfottantides metabolism of 122 I 231 Sulfumethovazole and trimethoprim See Trimedioprim-sulfantclhoxaeole Sullamidochrysodine metabolism of 107 5-Sullamoyl.24-3-aminobcnzoic acid dcnvatives 610—613 Salfamylon See Mafenide acetate Sulfanilamide 269 27 If See also Sulfonamides antituberculur activiry of, 254 metabolism of, 122 123f Sal fanilamides, 269 crystalluria and, 274 renal toxicity of, 274 Sulfapyridine 277 See alst, Sulfonamides metabolism of 122, l23f Sulfasalazine 279 See also Sulfonamides azo cleavage in ISO 1511 metabolism of 107—1118 Sulfate cyclodt,strins 447 Sulfates, conjugation of 1141 115—116 Sulfarecin, 334 Sulfcnta Ste Suleutanil citrate Sulftnpyrazone metabolism of 114 Sulfisoxazole 276 276t See a/co Sulfonamides metabolism of, 122 1231 Sullisoxaeole acetyl 276 See also Sulfonattuides Srnjclure.based drug design 55 939—944 Stypven See Snake venoms Sulftooxazole diolamine 276, 278 See also Sulfonamides Subcutaneous injection, drug distnhution and Sulfonamides 268—280 absorbable intermediate-acting 276t absorbable short-acting 276t 41 5—6 Subcutaneous mycosis 231 Sublimare See Fentanyl citrate Substance P 857 Sabstitnenis librunes cr1 26—27 selection of 22—23 23t Substrate stcreoselectiviry 132 Subtractive deconvolution in combinatcmnul chemistry 50 anillne.substituted 269 br bunts, 278—279 classification of, 269 discovery and development of, 269 distribution of 274—275 excretion of 274 275 987 topical, 269 2711—279 toxicity of 122 274 275 Sulfones, 279—280 Solfonylureas 668—670 metabolism of 94 Sulforidazine, metabolism of 99, 10(1 Sulfur mustard, 394 Sulindac 758 active metabolites of I 35t metabolism of, 108, 143 l44f prodrug l'orm of 143 144f Sunykect, Chimenc See Basiliximab Supeocntical fluid chromutography, in combinatorial chemistry, SI Sttpcrparamagnetic substances 476 Suprane See Desflutane Supras See Cetixime Suprostonc 8251 Suramin sodium as antineoplastic agent 430 447 us aniiparusitic agent 264 Surfactants carionic 224—227 Surgicoti See I'lexachlorophene Surgifoam See Gelatin sponge Suritul Sudiutn See Tltiamylal sodium Surmontil See Trimipramine maleate Sustivu See Efavirene Sutilains 839 Symmetrel See Amantadine Sympathetic ganglia stimulation of 586—587 Sympathetic nervous system 548 Syrrtpatholytics 524 Sympadtomimetic agents 510 524 5311—539 548 central 510, 512—514 5121 direct-acting 530—532 a.ctdrenergic receptor agonists 532—535 receptor agonisr% 536—537 drug products, 532—539 receptor agonist.s dual a-and 535 steriroselcetivity of 530 532 structure—activity relationships for, 530—532 53(11 indirect-acting 537—538 mived-uctimu 538—539 Syn2869 245 Synapse 680, 6801 683 Synaptic cleft 680 6801 Synaptic knob 679 6791 folnte coen,.yrnes and 270—271 2711—2731 Syneicid See Quinuprislin.dalfopristin Synnematin N 318—319 Synterrin See Rolitetracyclinc bolate reduciase inhibitors and 275 Synthnlin 66)1 988 lndc.v antibacterial agents 247—252 Sycttlcrtcid St', l.evothyrc.cnicce srcdcncci Syntccciniccc Sc,' (lnytcccin uicieclion; Oxtocin nasal MIIU1IO1 Tecnpr.c Sic Acecacccinophcen TenapilSc'c' l)cetlcylgtccpicccc Tenectephase 18.1 '1mev, Sic Gccanlacine hydrochloride Tectiptcside 426—427 Teccccnccicc Sc',' Atenolicl 'l'ensilccn, Sec lidroplc'cccicuun clc),cride T Tacarvl Sic Methdila'cne Tachyphylanus 59(1 TecctaGel resins, icc c,cnchin,ctccrial cltctcccslry 49 Temcate 5cc l)cellcylprcipiccn Tacrine lcytlrlccltloriile,,S67 Tadal'aftl active sites iii, 29 31)1 Tepacccil Sc',' l)iethylprtcpion Tall's steric parameter l1:, 21 Tagacciet See ('icoetidinc 'I'aggiccg mctlc4s fec c,ctcihcccuc,crial Iihr,crics 52—53, 521 52c ti' I)i,tst'asc rallyucnyecccs 417 Talwin Sec Pcntae,ccicce Tantbtccor Set' Hec;cinidc ucetace Tacccoxcien, 433, 436, 7Kt -782, 7KIi agicctist/acctagccitist actions ccl 29 ctcetabcclcsnc ci KS l'antsulccsin, 54) Tc,cc,i,c'ttccci ,cue,heiciiccrc I Ic, erlew) Taccdcanl 763t 'rapacole Scc MelIt,cccai,cle Tapewtcrccc inleslaticcccs, 264-265 Targtwict 'I'eicccplacciic largretin Sic Besacictetce I'argretitt gel Sec Bexarcccene Taetraiine nce)abolisccc ccl, 1117 Taxis) Sec ('lecccastinc iucnarace 'lax,') Sec Pactitasel Tascctere Sic' Dccceta',el Taylor serie' espaccsnccc, ')25 i'ancrotene 874- 875 T.widictce Set' ('eftaiitlicccc s,cclinccc 'ra-,obactacct, 3)5, 316 I'aiohactanc—pcperacil)cn,3 lb 'l'a-c,cr.cc,Sc'c' l'a,arotccte Sic Teclcccetiuccc "IC T cells 2(W) 21)2— 2)1:! helper 21$) 'lea bags, in comlcinac,crial syctllcesis, 4-4 45) 63 Tecelecckin Sec Aldesleukcn Tectcccetitcccc aibtincin aggregated 4(c3 —4(c4 Iechnetitcccc albumin c,clloid iccjecticccc 464 'l'echnetcum alhucccin injecticcn 463 Teclcccetiuctc apticiile 464 Teclcneciucn hicisace injeccccccc 464 Technetinm dcprectide injectciccc 464 l'echnetinnc di'.oIeccicc cn)eeciccn 46-I —4(iS Techccetincn exacccetaiicce injectiiccc, 4(cS Tecltnetiuccc meclronate injeccivctc 41c5 'l'echnetcucn ntcrtcatide iucjectcocc, 465 Technetium pentetate injection 466 I radiciplcarncacenlicals Teclcnetinccc 462 —467 Technetiuccc red )cl,cod cells lanrcchcgtcccs I 46(c Technetiunc sestacnihc cnjevtcon 466 Technetium sodium penechnet;cte 466—467 'technetium sciceccuer iltjecticcn 467 'l'echnetium sulfur coliccid injecticccc 467 'l'echneciucci tecrcclivsncin injecticin 467 Tegatccr 4)17 Tegisccn Sic Etretinate 'l'egccpen Set' Closacillin s,cdiccucc Tegretccl Sc,' ('arbama'iepiccc Teiclcccmycin Ste 'l'eicoplactin l'eicicplaccin 356 'l'elnuivartan lilY Telicncerase inhibitors, 448, l4()i Tencaril See Tricnepracicce Ianr.,te 'l'ecna,epam, 49! l'emosate 'Sc',' ('hohecascil prccpconate 'l'er;c,ol Sic' Tere,cnancle Teracosin 54(1—541 541c 'l'er.ce,csicc hydrccchlccride 652 Terbinaticce Icvdrccehhccride 23') 'lerbucahine, 536 Thalassencia ttcalaria acid, 283 iltalitone, See ('hlnrtltalid,cne Tlcallinnu r.cdiccplcannaccnticals 472 '11w llermlcydrocatcctahinccn 521) 522 ncetaholisctc ol, 66 77, 771 'J'hehaitte 732 735 745 Theohroincne, 511—512 SI It 'l'heophyh line as centritl ccers'ous sys)ecn stintctlant 511—512 SIlt as diuretic 618 as ncnscle relaxant 624 'flteriiidide, Set' Sccdiuctc i,idide 1131 ntelaholisnc cci, 87, 115 126 Tcrcona,ccle 243 Tlcermodytuactcic cycle 935 Tliiabend,c,acle 265 Ttciambutetce, 742 Thiamine 885—887 Terfeccadicce, 712—713, 7131, 94S Thiamine hydrochloride 886—887 Tercccicual hccttccns, 1c7'), 679) 'terc—.ccnycicc,Sc'c' Oxytdracvcliccc hydrccclclccrcde l'eslac,Sc'c' l'estcclactcccce Tessah,ccc, Sc-i' llen,ccnaca)e 'l'tciamiuc ntccccucnitrate, 887 'l'hiacccvlal ncetahccliscc, ci)' 81 Thc&crccylal siiditcnt 487 487t Thca,ide/chiaaide-like dinretics 6)15—6111 (cWct 6) Itt, 6071 6(18! Sc,' ,iLc'c' Diuretics Testolactccne, 436 783, 784), 785 as anccneicplastic 434 'l'estcislerccne hcological activity icE 797 798! hivcsvuthesis ol, 76')I, 77)) 7741 775 797 adverse effects ot, (illS tOY drug cnceraetiiitcs with, 609 cccnsec'si,ccc olin estradiol, 783, 7831 tndicarccms Icir, 609—610 (c07—IitlK, 6081 pharmacokiccetics preparatiocts cci, 619—624) ,ccet,cbohcsnt 'if, 71)7 site actd meclcanisccc of artion id, 608 preparations iii' 7991 8)81—8)11 stcluhility oF 770c structure—activity relaticcnships (icr 7')8— 799, 798c 'I'estostercinc cycliipentylpriipicinate stnccture ccl 7711 'I'esl,cs)erone cs'pitcnate 7's), K)) I structure iii, 7711 Testccstercccce enthanate 799, 8))) 'lest,cster,cne propicinate as amucceophastic 434 scilubihity ii!, hot Testred Sic' I 7a'Metlcs'Itescccstercccce 'lest sets, selection of 22—23, 23c, 26—27 i'ctanus toxoid, 21 2t, 214, 215 Tetrac.,ine 69(1—693 69!! 2.3.7,8.'l'etncL')clicrcidiben/op-cliox,cc c1'C('l It cnetaholism at, it, loll 'l'ctr.ccyclinels).34 I - 349 ehelates i'i.342—343 chectuistrs ti) 341 epiccceriiaticcn of, 342 scniccuce—activity retatitcn.s)cips Icir 64)5—6))?, 6(811 bUtt l'hia-,ohittdiones, 671—672 Thcenatccyeimsb3l5 316—317 Tlcimercisal 228 Thuciguanine 40)5 412 Thicipental hipophilichy at icuetahuclism cci, 99 Tlti'cpental sodiucn $87, 487t 'I'hiciper.,mide 728—729 7291 Tlcioridazine, 499—5)14 499t, 5)12 active ctcetatxclites of, I 35, I 35t tctetah,,lisict of, 99 l'hiotepa 395 4112 l'hiotlcivene 5)81 Thiccuracil 673—674 'llconeylacnitce hydrochloride 704 706 Tlcicra,cine 5cc Chlorpt-vcntaaine 31).QSAR 23, 38—39 31) structural proteiti database 939 9391 Thrcctcthiuc, 664 ((iS, 857 inacccvatccin ccl 342 cnechanisccc ccl action ccl, 343 Tlcroncbccnuridulcn 6(iS micrcchial revistactce to, 343 pK,, values (icr, 342 342t polar 345 'l'hrccccchosane A2, 666—667, 820), 8211, 822i prcxlncg fccrnc tct', 149, 15)11 Tlcrottthcipla.stin 663, 664, (c(i4t, 664t l'hymineless dean,, 41)1 Tltycccol 222 Thyrcccalcic'cnin 855—856 pricperties id' 344—,U5 345t spectra!! ccl activity ccl, 343 —344 sterecx'henctslry cit 3.)! 342t viniccure- activity relationstcips 6cr, 344—345, 'licyrogect Si',' 'l'hvrtitropicc alpha Tlcyroglohulin 857 Thyroid Itorcicones 673 Thyroid-sticnnlatcng hormone 1TSI-li, 845 ilcyroliherin 84(1—841 structure cit 34 1—343 342t 'l'etr.ccycline 'l'hyricpar Sic l'ttvrvcid-sticcciclatiug hccnn,cne (TSH( -l etraethylancnc,cctcnttt bnc,ccide 588 'l'etr.irthvlatnntoccinccc eIcI,cride 588 letracttcylauttcctonicccct salts 588 Tetraettcyltetrapltosphate i'F.F.Pt 569—57)) Tctr.clcydroc,'atcn:,hcnol (Tl-1('l 520 522 mecatxchiscci oh 66, 77, 771 'l'etr,ulcvdrcil,chic acid 4183—411), 411(1 l'hyrcctropict 845 'fltyruccrccpict alpha 176 Tetcahydoceoline S33 l'(i Set' 'l'hiiigtcactinc 'l'iagahitcv 5117 T1l'colone 796—797, 7971 Tccar, Se,' 'l'ictcrcclhicc ,lis,cdinm 'II IA Sc',' Tacrine hsdrvcchlciride Ticarcillcn—clavn)anate,3 Ifi 'l'etriidocccs,ct, 694) 'l'hyrotropin.relea.sing ltormone (TRH I 840-84! -Thyricvine 673 accalogtces developttcent ccl, 94(4—941 Index Tkanillin disodium, 309i, 314 Se,' Oh,, Penicillin(sl TiclicLS,'e Ticlopidine l'iclopudine (,33—634 Tigemonam 334 Tikosyn Sic Doretilide FiI,tdc See Nedocismtil sodiunt Timcntin See CIavulat,ate-tk.arcillin Timolol 543 5441 Tinioptic Ste Timolol Tinactin Ste Tolnaftule Tinctures, 219 Tines, 231) 23) 2311 233—235 l'ioconaiole, 242 Tipranavir 942 Tirapaiansinc activation of, 153 1541 Tirofuban, 634 Tissue depots Tissue plasminogcn activator (tPA) 1114 recombinant 1114 III.)) 840 $59t Tissue lhromboplastin 663, (,64 6641 Tts.'.uc tropism 371 Tiranidine, 534 Tobramycin sulFate 340 TOC-039 333 Tocamide hydtm.hloridc 640 half-life of Tocopherols 879—882 See aixi, Vitant,n relative polencies of 880 8811t Toc,,trienols 879 Set' aLso Vitamin E ToIranil See Imipr.,mine Tokosimide 669 Tolazoline, 539 Tolbutamide 269 668 669 metabolism iii 77 132 age and 126 Tolbutantide sodmiTi 61s8 Tulectin See Tulmclin Tnlinase.S,s Tola.zun,ide Tolmetln, 7511 metabolism of, 77 Tiili,aftale, 239 Tunocard Si', Toca,nide hydrochloride Topamax See Tupir.,mutc Topical anesthesia 687 See ufco Local anecihetics Topiramute, 507 Topological ,kscriplors, in drug design 23—24 24, Toradol 5cc Ketorolac tromeihamine Toremilene, 434 436, 781 7811 782—783 Tornulate Sc,' Bitolterol Torscmide 620 207 215 Toxoplasmosis, 260 IPA (tissue plasininogen actisaturl 1114 recombinant, 184 1841 Tntcclccc linkers, in cot,,binatorial synthesis 49 Trjcriu,n See Atracurium hesylate Tr,,c Tab See Phenyl salicylate Training set 25 Tratnadol hydrochloride, 747 Tramcinolonc acctoi;idc, structure of, 7711 Trundolapril 648 Transcription, 162 1631 192 193 Tranvdcrmal contrucephses 793t 794 Trunsducins, 871—872 Trnnsgenics, 94 leans isomers, 3) —32 of acetylclioline 34—35 34) Tr.,nxene Sc,' Clorazepate dipolussium Trunylcypromine sulfate 515—5)6 5151 Trastuzutitab, 190 as anhineuplastie, 443 Trjvuse Ste Sutilains Travatan See Travoprost Trusopt See Dor,olamidc Travoprost 82)1 Trazodone 519—52(1 Trecutor SC Ethionamide Trelstur See Triploralen pomoate Tiypanosomia.sis, 260 'l'rcmatode infestations, 265 Tremin See Trihexyphenidyl hydrochloride Treprostinil 823 Tretinoin 873 antineoplastic activity of 430 Triacetin, 233 Triameinolone relative activity of $091 Triameinolone icelonide, 8091, 814—815, 8)41 Trlumcinolone diacetate $13 Tnamcinolone hexacetonide 8)3 Tnamlcrcnc 617 620 Tnamtcrene.hydmchlorotl,iaride 620 Tnazolam 492 Trichilormethiazide 605—610 (106t, 608t Trichloroethanol, metabolism of, 112 Trichomonia.si'., 260 Tnclofo, sodium 496 Triclos See Triclofos sodium Tricor See Fenoftbrale Tn-Cyclen See Norgeslinsate Tricyclic antidepressants, 5l6—519 tttetabolism of, $7 Tridesiol See Descinide Tridihcttethyl chloride 584 Tndtone See Trimethadione Tn-Esl See Estriol 'fnetbyletieittelamine 395 Trilluorothytitidine, 407, 4081 Trifiuproma,.ine hydnichloride 499, 499t Tnhluridine, 376, 407, 4(181 Triglycerides 657 Trihexyphenidyl hydrochloride 584 Triiodothyronine 673 Trimegcslonc, 7871 7119 'rriinependine 736* Trimcprarmne tartrute 7l1 Trimetbadione 505 Trimehhaphan, 588 Trimelbapltan cumphorsulfonate 58$ Trimelhaphan camsylate 588 589 Trilnethoprim, 276t 279 mechanism or action of 271 metabolism of, 93, 98, 133 structure of 9421 Trimethoprim analogues, development at, 94l—942 Trimcthoprim.sulfametltoxatole 272 indications for 269 270t Trimeton See Pheniramine maleate 989 Trypanocidal agents 668 Trypsin crystallized 838, 839t Tryplophan Hopkins-Cole test for, 834 metabolism of estrogens and 893 TSPA See Thiolepu Tuberculosis, 254 338 drug therapy for 254—259 See also Anhitubcrcular agents Tuberculosis vaccine, 2)2*, 2)4 Tubocurarine chloride 590-591 Tubuloglomerular lecdbucL 599 Tumor cells, properties of 390—394 Tumor'infiltrating lymphocytes 442 Tumor necrosis factor 44(3 recombinant, 183, 447 Tusscapine See Noscapine 2-PAM prodrug form of 157—lStl, 1581 TXA2 Set' Thromboxane A2 Tylcnol See Acetaminophen Tyrocidin 299 Tyrocidine 360 Tyropanoace sodium 484 Tyrosine Miller's test for 834 'l'yrosine hydrunyla.se 524—525 5251 Tyruthricin 359-360 Tyzine See Tetruhydrozoline U U-46619 8251 UCN-0l 439 UDPGA in glucurunidation 112 UDP'glucumnyltransferases 112, 1)21 Ugi reaction, four-component, 49, 5(11 Ulcers, peptic 718—719 Ultiva See Retnifentanil hydrochloride Ultrtilente insulin, 851t 852 $521 Ultram See Tramadol hydrochloride Ultrasound contrast agents for 477 Llnasyn See Ampicillin-sulbactam Undecylenic acid, 233 Unipen See Nalcillin sodium Uniprost 825 Unoprostone 828 Ureas 506 Urecholine See Betitanechol chloride Urinary analgesics 253—254 Urine sulfanilamide solubilily in 274 Urised See Methylene Phenyl salicylate Uritonc See Melhenamine Urokinase 840 Urotropin Sec Methenamine Trimetrexute 410—411 Tritnipraminc maleate 517 Tripelcnnum,nc 704 705 metabolism of 87, 114 705 Tripclennamine citrate 705 'rripelcnnutninc Itydrochloride 705 Triple sulfa 278 See aix,, Sulfonamides Triprolidine hydrochloride, 709 Triptoralen pamoate 437 as antineoplastic 435 Trisenox See Arsenic trioxide l'risullupynmidines See aLso Sulfonamides oral suspension 277 tablets, 277 Trivalent oral polio vaceine 2)0 2121 'l'roleandomycin 353 Tropeines 676 Tropicamide 585 Tropinc 575 676 6771 Tnie salol 755 V i (Chttrton's steric parameter), 21 Vaccittutton, definition of, 207 Vaccine(s), 207 acellular 207—20% administration schedule for, 2121 215—216 bacillus Caltnette-Gudrin 2)4 u.s antineoplastic 440 .142 bacterial 2l2t, 213—215 booster, 2011 chickenpox 211 212t cholera 2121 214-215 coadministered 208 definitiott of 207 diphtheria, 212t 2)4—215 dosage of 208 DPT 212t 215 lluemophllw inflttenzae, 2121 214 990 /ot/it Vectmtrs cltttimtg, 11m5— (66 1661 468 dascoven' uI, 866-867 hepatitis A 211—213 21 It hepatitis II 2t 2(3 85th 116th hepatihis 1' 213 hepatitis E 213 Vectrttt Set' Mimtoeycline liydrochlonde Vecuntttitmui broittide, 593 luuctttmus ot' 866 human mmtiuunttdeltcter.cv situ' 182—3(11 Venial astue 519 Vettograptty 479 Vaccinet s (nutiinut'd# tttlltieiiiti, 2(8) killed btnaemhaledh 207 live/attenuated 2(17 malaria 283—285 measles 2111-211 21 2t meutugococeal pol) saceharide 215 multiple-dose 2(18 mulimvalemtt 208 S'eloset Sec Cephadritte Ven Apis Set' (lee veuout' Vemttstns 835 Venmttlitt, Set' Albuterol VePestil Sic Etopctsitle Vcrapanttl us atitiarrttytbinic 1.42 is sasttdilator 629 629t Verltittp's titultidititetisittual sterme parattteters mumps 211, 2l2i pcm'tussis 212 213—214 pharmaceutical principle' 248) pneutntmcoccal 215 polio 2(41 21 2t polysalent 208 production itt 2447—2148 recoutbmuant 186- 187 187 24(8 21)81 rotavmnis 213 rubella 2111 21 2t Verluma Kim See Noktitmomoah tnerpetuan Vermtios, See Mebeudaiole Veiiimteautine, 728-729 7291 Verstr,ttt Sec Prucepatit Very- ((((v-density lipoptoteitts 658—659 85(1 Vesprin Sr.' 'lrillttprotmtaiiue ltydrttclmliiride Viagra See Sildeitalil Vihe,tnvccitt See l)ovyeycline labeling requtrettteuts for 866 866t lipid-soluble 866- 885 overview ut, 866—867 recommended daily intake iii 866 ShOt supplemnetttal indications titr 86(i scaler-soluble 885—918) Vitatmmiu A 867—875 hitueheniical Ittttctiitns ,t(, 87(1 biological activity at 867 biosynthesis uul 869-8711 etilite reaction', 55 itlt, 869 crystalline 869 deficmettcy uI, 8711 delimmititiu mit, 868 dietary sources cit 868, 868t, 869—870 eneecs of 870—871 in ft,slt liver oils, 8(m8t, 869 isttttters 01, 868, 868t 872 tttechuttisns al actittmt itt, 872 mciubuilisttm o1, 86') uutttberiug system [or 868 Victtttmtycin, 417 Vidar,tbitte -'cci' Adetitisitte arabmnosmde pruxlttcms 872—875 sitmule-tltise, 208 stmtallptis 2(19 storage tin1 hattdlitmg ot 2(49 tetattuc 212t 214—215 tubercuhicts 21 2t 214 vir,tl, 21(9—213 367—3744 Vtttti,titmt spp bcmttnberrs' '112 S'ides See Didantisitte Viublastitte sulfate, 425 41St 427 retinoie acid receptors and 872 Vinci alkaliitds, 324 425 425t 9(5 structure—activity relationships for 869 Vimicristtmte sullate, 325, 41St 427 Vtmtesine 425, 425t tosictty of, 8711—871 Vaginal ritig contraceptive des ice 7'11t 794 Vagistut See Ttocoua,,tle Viutirelbine tartrate 427 Vinrosiditte, 425 425t Viuyl chloride tttetabttlisnt itt', 77 Vuititrtmt See Ultitqttinol simple 20$ Vinglycittate 425 425t Vimmleiut,sitte, 425, 425t Valacyclovir hydriicltlt.rtdr 377 Valdecosib, 76(4 822—823 Vajeriau, 914—915 Valium l)itmeepani Valnthiciu 416, 423 Valsatlan, 64') Val',tar See Valnibictu Valtres Set' Valacyclos ir hydtttcltli'ride Vancettase See Ileelitittetltasotie diprttpiotmate Vauceril Sit' Ilecloutetlvootte tltpriipiouatc Vancitctn Sic Vancontycin Itydnicltloride Vaucoled.St'.' Vauc,tmi.vcitt Vamtcittttyciu 34 Itt Vattcitntycitt hydrttctdortde, 355 356 Van der Waals' Iorces.3 I 34 Van der Waals' sttriace in tt.otrcttla tmulelotg 922 9221 Vauostde Sit' Hydrotis beutityl peroxide Vansil See Ovammtmtiqtttne Vautiu Set' ('elpodositne proxetil Vardenal'il u,'tive sites ut 29, (III Variamycins 4(7 Varicella vaccine, 241 21 2t Vitatttmn 8145 1487 tlelicieticy itt 891 Viracepi 5.'.' Neliluavir diemttry ctturces of K')2 Viral imtl'eetions, Se.' ohiti Viruses htttxi in 367 cattcer ,tttd 372 clteutopropltylasis (tie 372 tosis in .171 host-virus interactions in, 371 tititoutti/ation (or, 2(8/- 213, 367—3711.5cc discovery at, 894 alt" Vtteciuebst prtuhtenve 367 stages all 3744—372 Vieamtttttiiitr Set' Nesirapitte Vtrioti, 172 'l'rilluridine Virtual screenIng, 54—55 56, 63 919 Viruses See ti/ia Viral itikctitms building of 372 lmttnmttttmes antI 893 $t(4 products 894 pntpenies ttf, 891 —8't4 Vitatnin Be 89l896 deficiency at 895 tctltc acid metulxilisttt ttd 896 897 potdttcts SQS—891m properties uti 894—895 titsicity of, 8115 Vtma,otu Rix 894 Vitamin C 898—1499 Vitatuin 1) 875—879 absturptittu iii 877 hiolttgteal activity utt 876 hiosyutttesis iii 875—876 cleissiflcammt,u t,l, 167, 3681—37(11 deficiency tit, $76 ttietary stutrees it, 877 l)NA 368t 37th 372 eveess all 876—877 oTicogenic 372 overs-iesv iii, 167 mephicahlttu 1,367, 371 372 KNA, 139t 36Km 371—372 toeiabttlism id 875 cltar,tcteristtes ol, 367 Visken Set' I'intltilol Vtsttde cc.' (3dolttvit V stray Set' Ovypheueycliittine hydrochloride Visual purple 871, 872 Vasttpressimm tzutuate 8-tot $47 Vist.al 870 Vitaniitttst, 866—94(2 tlaily values ut 866 8661 V-Cillitt Si'.' Penicillin V Viiamtmimm A., $75 Vilatitimt B,, 1191 894 ntechanismtt itI actiott ot, 4,22 623 tt2it ntetabvtlisnt itt', 623 623, tt25t Vasopressiti, 845 8.16 Vasopressin iuieetitm 8-lbt, $47 Vasox> I Si'.' P,letltttsamutne (,'SP 872-873 itt visittu 870 871—872 Vitttmiu A1 867, 168 Viiivs Ste Ritlecosib Vtsn.e Sit' 'fetretltydr.vtolttte Vistou s ttamttmtm A tnd 870, 872.873 eycltidesiritt uttits nil, 86%, 868t S'iotm.yctmt 259 Vaccutr St-c Ilepridil ltvdtimchmlortde Vasoaettve intestinal ps'ptttle 1455 Va'.ocouctrtctitts, mt local anesthesia 688 Vasrulilators, ('22- 1.31 antianginat 622—626 See u/tie Nit retva.sititilators antittypertetisive 1.53 1.54 ant,thrittmtbotic 1t32—634 Vasuprost See l'rostaglaudiu Vasotee Ste Ettalupril stereoeheimtislry of 868 Vumamin B: 89(1—1191 Vitamin 887- 1488 Set' Adenttsiue arahinoside Valprote acid, 51(6 mttetaholisttt tit St pros itautitis, 869— 87tt tissue mt'opismtt at, 371 tutcoatimtg tI 371 deliciencies al, 866 dieiary reference intuhes t,l, 866, 867t products 877—879 potperlics tIll 1175—877 tttsiciiy utt 876 1177 Vitamtiin I) receptors 877 therttpcumic uses uI', 1477 Vitamitu F, 879—1112 absi'rpiitiu al, 88(1 881 autiosidaut properties uI, 8811 -XIII deficiency oh 881 dietary s.tttrees at 879—812 discosery till 879 tu:tclivatiou uI' 881) isttltunos ol, 879 —8811 ttteg;tdoses tiE, 881 u,etahttlismtt at' 881 propetties cut 88tt Index African sleeping sicknc'.s 260 Wes(heimer method, 923 Whitfueld's Ointment, 234 Wilpowr See Phentermine hydrochloride relative poicnctes ol 88(1 8818 of 881—882 thcrapcuttc Vitamin G 890—891 Vilantiti K 882—1(85 ihsiirpliiin iii 883 anticoagulant activity of, 665 fi661 dictar) sources ut 882 t182t discovery ol 882 Iuiictutms ni, 883 iiictaholism of 883 VP I (i 'i'i'i' Wycillin St't' Penicillin (3 procaine Wydase Set' Hyalumnidase (or tnjection Zan,nlin.St't' Ethi,susimide Zarsixotyn Sit' Wytensin, Set' Guanahcne acetate Zebeta Si-u' Bisoprolol '/.cfaione See Crtmeia,ole sodiuuti, Zcmplar Set' Paricalcitol x Zcntel Ste Alhetidazote Zcphiran.Si't' lIeuw.all.tiniiutn citloriule Zerit Set' Stavudine Zero modulators 489 Xaltutatt Ste Latittiopront Xanax Ste Alpruaolum Xututhincs, 511—512.51 It Xanthoproteic test, 834 Xcloda See Capecitahinc Xenobiotics definition of, 65 Zesiil.Se.' Lisinopril Zcvulin kit Sit' Ibritumomab IluSetan Zidiuvudine, 379—384) Xenon r.udiopharmaceutucals 472 Zikuton, 820 Xigris Sue Rotrceogin alfa Zitiucet See Cefuroxime sodium Zinc caprylale, 233 Zinc propionate, 233 Zinecard See Dexrtuiuxanc S i'.xinters, 32 321 Zithrtunuax Si'.' A,.itbroinycin 7,ocor Set' Sjnis'asluiin Zolades Sit' Goserelin Zuloll See Sertr,iline Zolpidem, 492 Zonegran.Sei' Zsunisainide Zonisamide, 507 Xipamide 607—6111, 6071, (i09t, 621) Vumon Sri' Teniposide Xupenex Set' Levalhuterol X-ray crystallography, 37—38 X'ray films 454 472—473 w Xylocaine St'i' Liulocaine hydrochloride Warfarin active mclatxilitcv iii 1351 metabolism ul, 10 105 32 sites ut action of 1,61,1 Warlarin potassium, 1,1,7 —Wit) Warfann sodium 61u7 Waler, a' atliphaleric sutistance II soliuhility pK, and I Waler-soluble vitamins, 81(5—'XK).S Vitamin(s) Water solvent models 934 Watson-Crick DNA r,ioulel, 921t Weicliol Set' Colesevelant Welibutrin See Buipropion Wellferuin.S,'u' Inlerteron I Xylometai.uulune 537 454 V YA-56, 417 Yeast infections Set' Eungul infections See Induuquinol Jut Zalcitahine, 380—381 Winstruit Set' Stanorolot Wyumycin See Erythromycin steurute products 884—1(85 iclaliotiships 1(82—883 therapeutic usc' iii, 883 Vitantiti K1, 884-885 Vitamiti 882 Vitamin K 81(2, 1(85 Vitamin Ka 882 Vitamin K inhibitor' 1,1,7 Vi' actil See Prutriplyliue li)drui.liloride VM-26 Set' Voltarcn.S,'i' l)iclotcn.ic 'odium Vorici,naiok 244— 245 Zaditor See Kecotifen tumaraw ophthalmic solution Zaleplon 41)2.493 Zanafles See Ti,aniditte Zanuisar.Si'e Strepto,.ocin Zantac See Ranitidine Wine spini St't' Alcohol Yoltimbinc, 541 See Niclosamide Yutuupar See Ritiidnne zorhaniycin, 4(7 7.orbnnamycins, '1(7 Zosyn Sit' Taeohactam.piperacillin Zovirax See Acycliivir Zytlo See Zuteuton Zymiigcn granules, 838 Zyittogen'., 1(37 z 7,actanc Citrate See Ethoheptarinc Zactirin Set' Ethohepluzine 991 Zyprexa.S.'e Olaticapine Zyrtec Si'.' ('ettnzinc Zyvuis Set' l,inezisl(d ... Professor of Medicinal Chemistry and Director of Professor of Medicinal Chemistry Professor Emeritus of Medicinal School of Pharmacy Mercer University Atlanta, Georgia Chemistry Department of Pharmaceutical. ..Wilson and Gisvold's Textbook of ANIC MEDICINAL AND PHARMAC ICAL CHEMIS TRY E L E V E N T H E D I T I N Wilson and Gisvold's Textbook of ORGANIC MEDICINAL AND PHARMACEUTICAL CHEMISTRY ELEVENTH... gentleman and leader of pharmacy education and the pharmacy profession John H Block PREFACE For almost six decades, Wilson and Gisvo!d s Textbook of Organic Medicinal and Pharmaceutical chemistry