567

Index

Bold page numbers = tabulated PK data

a852 A 418abacavir 438abanoquil 425abecarnil 299abiraterone 483abortifacients 490, 539, 541Abraham, Edward P. 522absorbtion of drugs 14ABT-263 365ABT-279 345ABT-761 194ABT-869 371acadesine 428acamprosate 203, 204acarbose 81ACE inhibitors 99, 162, 335–340, 352acebutolol 324acecainide 216aceclofenac 506acefylline 441acemetacin 503acenocoumarol 60, 143acepromazine 305acesulfame 208, 434acetals 138acetamidoeugenol 42acetamidofluorene 133acetaminophen (paracetamol) 84, 92– metabolism 82acetazolamide 451, 457acetohexamide 37, 139, 458acetophenone 594-(acetylamino)antipyrine 181acetylcholine 118, 393acetylcholinesterase 118

acetylcholinesterase inhibitors 245, 334,399, 420

acetylcholinesterase reactivators 398, 399acetyl-CoA 15, 145N-acetylcysteine 99, 162, 339acetylenes 40N-acetylhomocysteine 162L-acetylmethadol 165, 237N-acetylprocainamide 216acetylsalicylic acid 164, 349, 497, 512acifran 510acipimox 70, 398acitretin 153acivicin 160acne 152, 153, 481ACNU (nimustine) 69ACP-103 257acridines 413, 416, 420acrivastine 145, 231acrolein 55, 205acromegaly (excessive growth) 360actisomide 238active transport of drugs 15, 16active tubular secretion 15acute coronary syndrom 366acyclovir 437N-acyl amino acids 147N-acylcyanamides 146acylguanidines 122, 123acylhydrazines 137N-acylsulfonamides 146N-acylureas 193adamantyl group 37adapalene 152adefovir dipivoxil 210, 443adenosine 436

Lead Optimization for Medicinal Chemists: Pharmacokinetic Properties of Functional Groups and OrganicCompounds, First Edition. Florencio Zaragoza Dorwald.© 2012 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2012 by Wiley-VCH Verlag GmbH & Co. KGaA.

568 Index

adenosine A1 agonists 438adenosine A1 antagonists 442adenosine A2A agonists 437adenosine A2A antagonists 245, 442adenosine deaminase inhibitors 444S-adenosyl-L-methionine 15, 436adimolol 48, 327adinazolam 471adjunct antineoplastics 254, 367adrafinil 146, 157adrenaline 3, 267adrenaline receptors 225adrenergic agonists 273, 281–283α2-adrenergic agonists 126, 130, 275β3-adrenergic agonists 24, 281α1-adrenergic antagonists 278, 279, 416,

425, 426α2-adrenergic antagonists 125, 299, 380α-adrenoceptor antagonists 246β-adrenoceptor antagonists 195, 320–328adrenocortical steroids 477–481adverse drug reactions 17–20afatinib 373aflatoxines 41afloqualone 50, 136, 419AFN-1252 171AG-1343 351AG-14699 300AG-337 418agomelatine 48, 275agranulocytosis 18, 19, 173ajmaline 298alacepril 167, 339alafosfalin 209, 211alanine, as solubility enhancer 166, 167alatrofloxacin 167, 516albaconazole 389albendazole 385albendazole sulfoxide 61, 188, 385albumin 6albuterol 284alclofenac 499alcohol dehydrogenase inhibitors 379alcohols 71–81– acidity 40– prodrugs 164, 186, 213, 214alcoholism 194, 204alcuronium 300aldehyde dehydrogenase inhibitors 194aldehydes 138aldose reductase inhibitors 153, 163, 178,

201, 502aldosterone antagonists 487alendronic acid 211

alfacalcidol 489alfentanil 243alfuzosin 425alinidine 126aliphatic amines 107–117aliskiren 168, 349, 357alizapride 218alizarin 89, 495alkanes 35alkenes 40–44alkyl bromides 53alkyl chlorides 51, 52alkyl fluorides 49–51alkyl groups 35alkyl sulfonates 54, 206alkylating agents 49–56, 206, 300alkynes 40allergic rhinitis (hay fever) 225–227,

252–258; see also antipruritics, histamineH1 antagonists

allopurinol 439allylamine, pKa 110allylbenzenes 42alminoprofen 499almitrine 41, 253almokalant 326almorexant 288almotriptan 293alogliptin 342, 435alosetron 381alovudine 432alphaxalone 483alpidem 52, 410alprazolam 470alprenolol 320, 322alprostadil 539altretamine 398alvimopan 168, 239, 330Alzheimer’s disease 245, 297, 353, 355, 417α-amanitin 347amantadine 37, 115ambrisentan 151ambroxol 117, 136amdinocillin 526amebicides, see antiprotozoalsameltolide 344amezinium 407AMG 706 366amides 166– as prodrugs 114, 167amfenac 500amfepramone 270amfonelic acid 516amidines 120

Index 569

amidopyrine 181amifampridine 398amiflamine 273amifostine 214amikacin 79amiloride 123, 130, 408amineptine 313amines 107, 133, 225– basicity 40, 110– metabolism 110–114– prodrugs 112–114, 167, 187– rates of N-dealkylation 111–114aminoacetonitrile, pKa 110amino acid conjugation 15amino acids 147, 157–163N-(aminoalkyl)benzamides and -benzoates

215–224aminoalkylindoles 291–3004-aminoantipyrine 181aminobenzenesulfonamides 21, 4502-aminobenzoic acid 4984-aminobiphenyl 1334-aminobutyric acid, see GABA9-aminocamptothecin 423amino carboxylic acids 147, 157–1636-aminocaproic acid 157aminoglutethimide 136, 196aminoguanidine 128aminoglycoside antibacterials 78–816-aminohexanoic acid 157aminoisobutyric acid 3476-aminopenicillamic acid 522, 523aminopeptidase inhibitors 156aminopeptidases 166aminophenols 82aminopterin 5514-aminopyridine 395, 398aminopyrine 1735-aminosalicylic acid 511, 512amiodarone 17, 54, 261amisulpride 106, 218amitriptyline 101, 312amlexanox 495, 507amlodipine 108, 165, 449ammonium chloride (for urine acidification)

269ammonium salts 107, 118amobarbital 198amocarzine 194, 201, 371amodiaquine 414, 420amorolfine 273amosulalol 285amoxapine 318amoxicillin 526

AMPA antagonists 404amperozide 240amphetamine 270amphetamines 267N-Lys-amphetamine 270amphotericin B 561ampicillin 204, 526ampiroxicam 186amprenavir 214, 351amrinone 406amsacrine 416amylocaine 215anabolics 434anacetrapib 177anaerobic organisms 378anagrelide 131analeptics, see CNS stimulantsanalgesics– narcotic 149, 227, 228, 237, 239, 243, 251,

274, 278, 329–334– non-narcotic 84, 85, 126, 153, 181, 211,

235, 236, 270, 276, 305, 316, 330, 403,405, 455, 456

anastrozole 184, 390andarine 170androgen receptor modulators 170, 179androgens 477, 485, 486anesthetics– inhalation 53– iv 84, 116, 198, 199, 243, 281, 471– local 77, 84, 215, 216, 224, 236, 341–344,

483angina pectoris 66, 320angioedema 359angiotensin 335angiotensin converting enzyme (ACE) 335;

see also ACE inhibitorsangiotensin II antagonists (sartans) 335,

543–547angiotensinogen 335anidulafungin 359anilides of glycine 341–346aniline 133anilines 133–136aniracetam 172, 174anorexics (appetite suppressants) 125, 251,

268, 270–273, 280anseculin 247antabuse (disulfiram) 194, 202anthelmintics (vermicides)– cestodes 86, 264– nematodes 97, 124, 127, 194, 250, 385,

386, 562– schistosoma 74, 158, 183, 287, 288, 496

570 Index

anthelmintics (vermicides) (contd.)– trematodes 57anthracene 47anthracyclines 492–495anthranilic acid 498anthraquinones 495, 496antiacetylcholinesterase agents 118antiacne agents 152, 153, 481antiadrenal agents 56antiadrenergics 117antiallergics 247, 440, 478, 481, 495, 507,

510, 515antialopecia agents (hair-growth stimulants)

407antiamyloidogenic agents 204antiandrogens 170, 179, 481antianginals– β-blockers 321–328– calcium antagonists 227, 229, 474– carnitine palmitoyltransferase inhibitors

230– nitrous oxide precursors 66, 76, 401– phenethylamines 276, 277, 286– piperazines 252antiangiogenics (vascular growth

suppressants) 366, 371, 372antianxiety agents, see anxiolyticsantiarrhythmics– adenosine A1 antagonists 438– alkylamines 182, 233, 236, 238, 241, 257,

259, 261, 263, 285, 298, 307, 313, 345,422, 435

– amidines 125– ammonium salts 117, 222– β-blockers 321–328– calcium channel blockers 277, 474– guanidines 128– phenethylamines 276, 277, 279, 286– potassium channel blockers 117, 263, 463– sodium channel blockers 216, 217, 220,

224antiarteriosclerotics 399antiarthritics 79, 89antiasthmatics– β2-adrenergic agonists 283, 286– leukotriene D4 antagonists 422, 440, 509,

511– lipoxygenase inhibitors 194, 495– mast cell degranulation blockers 510– methylxanthines 440, 441– other 224– PDE4 inhibitors 151– steroids 478, 480– thromboxane A2 antagonists 150

antibacterials– aminoglycosides 79–81, 129– amphenicols 78– ansamycins 562, 563– antifolates 404, 405, 450– carbamates 176– diaminopyrimidines 404, 405– dyes 62, 512– β-lactams 522–537– lincosamides 78– macrolides 557, 559–563– nitrofurans 183– other 116, 160, 161, 210, 211, 317, 356,

384, 399, 417– peptides 361– quinolonecarboxylic acids 514–521– sulfonamides 21, 450, 458, 459– sulfones 87– tetracyclines 492–495antibacterial adjunct 162antibiotic resistance 523anticholinergics 118, 150, 221–223, 230,

233, 238, 303, 304anticholinesterase agents 118anticoagulants 127, 142, 143, 177anticonvulsants, see antiepilepticsantidepressants– bicyclics 159, 228, 231, 270, 275, 276, 280– hydrazines 400– other 176, 216, 217, 236, 237, 271, 273,

281– pyrrolidones 175– tetracyclics 125, 245, 247, 249, 266, 293,

317, 318, 471– tricyclics 230, 234–236, 247, 251, 259,

306, 310–314, 317, 406antidiabetics– biguanides 131– carboxylic acids 150–152, 163, 510– DPPIV inhibitors 8, 23, 273, 288, 342,

345, 346, 355, 435, 443– other 77, 78, 128, 129, 458– sulfonylureas 462–464– thiazolidinediones 178, 179antidiarrheals 237, 239, 241antidiuretics 360antidotes– for cholinesterase inhibitors 398, 399– for curare 85, 190– for ethylene glycol 379– for heavy metals 158, 159, 162– for methanol 379antidyskinetics (tremor suppressants) 217,

287, 401

Index 571

antiemetics (nausea suppressants)– dopamine antagonists 217–219, 244, 260,

304, 307, 308– histamine H1 antagonists 252–254, 303– 5-HT3 antagonists 219, 223, 381– NK1 antagonists 265, 266– THC analogs 86antiepileptics– acylureas 195– alcohols 74– amides 148, 162, 175, 354– barbiturates 197– benzodiazepines 466–476– carbamates 177, 189, 190, 404– carboxylic acids 148– dibenzazepines 316– GABA analogs 160, 161– GABA reuptake inhibitors 240– imides 177, 178, 196– sodium channel blockers 405– steroids 483– sulfamates 95– sulfonamides 457, 458antiestrogens 263antifibrotics 406antifolates 404, 405, 408, 409, 450, 551–553antifreeze agents 76antifungals– alcohols 76, 86 (phenol)– amines 116, 273– amino acids 160– guanidine 127– N-hydroxypyridones 406– imidazoles 387, 388, 391– peptides 359– polyenes 561– triazoles 387–392antiglaucoma agents 122, 126, 246,

321–328, 380, 385, 457, 540, 541antigonadotropins 485antigout agents 476, 510antihemorrhagics (hemostatics) 148, 157,

160, 182, 205antihistaminics, see histamine antagonistsantihyperlipemics, see antilipemicsantihypertensives– ACE inhibitors 99, 162, 335–340, 352– α1-adrenergic antagonists 125, 244, 248– α2-adrenergic agonists 126– angiotensin II antagonists 543–547– arylethanolamines 285, 286– aryloxyacetic acids 151, 155– aryloxypropanolamines 248, 276, 320–328– benzothiadiazines 452, 453

– calcium channel blockers 277, 279,446–449, 473, 474

– dihydropyridines 446–449– dopamine agonists 272– guanidines 126–128, 130, 400– hydrazines 404, 419– indole alkaloids 298, 299– other 159, 403, 407, 418, 488– potassium channel openers 174, 407– prostaglandin analogs 540– quinazolines 425, 426– renin inhibitors 357– sulfonamides 452–454antihyperthyroids 182, 201, 434antihypoglycemics 452antihypotensives 273, 282, 285, 407antiinflammatories, non-steroidal, see

NSAIDsantiinflammatories, steroidal 477–481antileprotics 87antileukemics, see antineoplasticsanti-Lewisite (dimercaprol, BAL,

2,3-dimercaptopropanol) 98antilipemics 86, 154, 155, 161, 205, 398, 510,

549, 550antimalarials, see antiprotozoalsantimetabolites 428antimigraine agents 95, 148, 159, 248, 253,

258, 291–296, 354antimitotic agents, see antineoplasticsantimony-containing drugs 158antimuscarinics 118, 232antimycotic, see antifungalsantineoplastics– alkylating agents 49–56, 141, 206, 300,

398– anthracyclines 492, 493– antifolates 408, 409, 551–553– antimitotics 291, 297, 298, 375, 554–556– apoptosis inducers 89, 194, 355, 365, 367– epipodophyllotoxins 89, 90– epothilone analogs 564– farnesyltransferase inhibitors 476– histone deacylase inhibitors 156, 360, 366,

367– hormonal 170, 179, 196, 263, 357, 358,

483, 486, 487– kinase inhibitors 22, 217, 258, 366, 368,

369, 371–375, 412– matrix metalloproteinase inhibitors 352,

353, 371, 505– N-nitrosoureas 68, 69– nucleoside analogs 418, 428–439, 444

572 Index

antineoplastics (contd.)– other 117, 157, 160, 194, 252, 255, 262,

288, 300, 354, 356, 357, 366, 370, 372,374, 375, 381, 386, 390, 402, 461, 505,509, 558

– platinum complexes 158– radiosensitizers 383, 564, 565– topoisomerase inhibitors 299, 416, 423,

424, 496, 516– triazenes 64, 65, 382, 507antiobesity agents 152, 171antiosteoporotics 88, 210, 260–263, 353antiparkinsonians– adenosine A2A antagonists 442– alkylamines 115– COMT inhibitors 83, 85, 86– diarylalkylamines 233, 257, 303– dopamine agonists 274, 275, 294–296– dopamine precursors 83, 159– dopamine reuptake inhibitors 251– MAO inhibitors 271antiplatelet agents 162, 465; see also plateletantiprotozoals– ameba 85, 382, 383, 417– giardia 183, 382– leishmania 127– malaria 62, 94, 95, 97, 131, 211, 233, 413,

414, 417, 420–422– pneumocystis 127, 141, 157– toxoplasma 141, 405– trichomonas 382, 383– trypanosoma 127, 157, 384antipruritics 77, 158, 254, 255, 304, 305; see

also hay fever, histamine H1 antagonistsantipsoriasis agents 153, 489, 509antipsychotics– benzamides 217, 218– butyrophenones 241, 242– other 240, 241, 244–247, 249, 250, 274,

287, 309, 311, 318, 319– phenothiazines 301, 304–308antipyretics, see antiinflammatoriesantipyrine 181antirheumatics, see rheumatoid arthritisantirickettsials 78antiseizure agents, see antiepilepticsantiseptics 82, 87, 132antiseptic surgery 82antisickling agents 151, 509antispasmodics 88, 117, 219–222, 227, 230,

232, 257, 261, 287antithrombocythemics 131antithrombotics– antiplatelet agents 162, 465

– factor Xa inhibitors 170, 176, 177, 266,363, 367, 370

– NSAIDs 500; see also NSAIDs, salicylates– other 180, 247– platelet aggregation inhibitors 265, 366,

439, 539, 540– platelet glycoprotein IIb/IIIa blockers

265, 361, 362– thrombin inhibitors 363, 364– thromboxane antagonists 149, 150, 156,

542– thromboxane synthase inhibitors 149,

380, 510– vitamin K antagonists 142, 143antithyroids 261antitumor agents, see antineoplasticsantiulceratives– histamine H2 antagonists 101, 132, 264,

377, 380–382, 402– muscarinic M1 antagonists 313– other 163, 407– prostaglandin analogs 541– proton pump inhibitors 104, 370, 396,

409, 410antiurolithics 439; see also uricosurics,

hyperuricemiaantiussives (cough suppressants) 221, 248,

260, 261, 281, 288, 329–334, 345antivertigo agents 401; see also motion

sicknessantivirals– CCR5 antagonists 253, 382– hepatitis 351, 436– HIV 200, 240, 253, 317, 350–352, 354,

369, 382, 405, 516– neuraminidase inhibitors 122, 129, 160– nucleoside analogs 209–211, 428–438,

443, 444– other 115, 127, 143, 190, 385, 418, 425– reverse transcriptase inhibitors 294, 317anxiolytics (fear suppressants)– arylpiperazines 249, 318– benzodiazepines 466–476– carbamates 189, 190– other 125, 199, 234, 256, 266, 299, 306,

370, 391, 410, 426apalcillin 526apazone 4apixaban 177aplastic anemia 18apomorphine 287, 334apoptosis inducers 89, 194, 355, 365, 367appetite stimulants 86, 482appetite suppressants, see anorexics

Index 573

apraclonidine 126aprepitant 214, 265apricitabine 431aprindine 236aprobarbital 198aqueous pores 14, 119arabinofuranosylguanine 438arabinosyl-5-azacytidine 430arachidonic acid 538arecoline 264arene oxides 45arenes 45arenesulfonamides 21, 450–460argatroban 363L-arginine 129aripiprazole 247armodafinil 157aromatase inhibitors 390aromatic hydrocarbons 45aromatic hydroxylation 45aromatic thiols 99artelinic acid 94artemether 94artemisinin 95artemotil 97artenimol 97artesunate 94arthritis, see antiarthritics, rheumatoid

arthritisarticaine 164, 344articainic acid 344artificial sweeteners 77, 79, 115, 205, 434arundic acid 148arylacetic acids 497–506arylalkylamines 225–266; see also

phenethylamines2-(arylamino)benzoic acids 498aryl bromides 53aryl chlorides 52aryl fluorides 50N-arylhydroxylamines 60, 1353-aryloxy-2-hydroxypropylamines 320–328arylpropionic acids 303, 497–503arzoxifene 260ASA404 505ascaridole 97ascorbic acid (vitamin C) 77asenapine 318asimadoline 278asoprisnil 489aspirin 164, 349, 497, 512astemizole 226, 258Astra 341, 396astrocyte modulating agents 148

asulacrine 416ataluren 508atazanavir 349, 354atenolol 3, 320, 326atherosclerosis 399atipamezole 380atomoxetine 228atorvastatin 46, 549atovaquone 141atracurium 290atrasentan 505atrial fibrillation 81, 330atropine (hyoscyamine) 223attention deficite hyperactivity disorder 228,

229atypical antipsychotics 240, 318, 319auranofin 79aurothiomalate 158autan 169avibactam 182avitriptan 248, 294axitinib 372azacytidine 430azanidazole 384azapropazone 180, 418azasetron 219azatadine 254, 315, 393azathioprine 439AZD 6140 439AZD 6244 372azelastine 258azetidine, pKa 110azides 58, 133azidocillin 58, 526azilsartan 546azimilide 108, 182aziridine, pKa 110aziridines 54azithromycin 108, 561azlocillin 527azo compounds 62azoles, see imidazoles, triazolesazomycin 378azosemide 454, 507aztreonam 208, 534

bbaclofen 160, 272bacterial fatty acid biosynthesis inhibitors

171bacterial infections, see antibacterialsbafetinib 368BAL (dimercaprol) 98balofloxacin 519

574 Index

balsalazide 62, 512bambuterol 284bamethan 35, 83, 282bamifylline 442barbital 193, 199barbiturates 17, 193, 197–199barnidipine 449basic drugs, see amines, amidines, etc.batimastat 352BAY 59-8862 556BAY-129566 505Bayer 193, 215, 446, 498bazedoxifene 261BB 83698 356bbb penetration 16BCH-4556 430Bcl-2 inhibitors 365, 375BCNU 69beclobrate 154beclomethasone dipropionate 478befloxatone 176benazepril 164, 339bencyclane 236bendamustine 56, 151bendazac 502bendroflumethiazide 452benign prostatic hyperplasia 278, 279, 416benoxaprofen 144, 501benperidol 242benproperine 260benserazide 137benzalkonium 118benzamides 215benzarone 88benzbromarone 53, 88benzene 47benzenes, see arenesbenzidine 133benzimidazoles 61, 378, 385, 386benznidazole 384benzocaine 215benzoctamine 306benzodiazepine agonists 299benzodiazepine antagonists 471benzodiazepines 60, 169, 466–476benzoic acid 145, 511benzoic acids 497, 506–513benzonitrile 59benzphetamine 273benzpyrene 47benzthiazide 102, 452benzydamine 236benzylamine, pKa 110benzylamines 116, 117

benzylisoquinolines 269benzylpenicillin 204, 522, 527bepotastine 257bepridil 136, 227beraprost 540besifloxacin 519besipirdine 403beta-adrenergic, see β-adrenergicbeta-blockers 320betahistine 393, 401beta-lactamase inhibitors 182, 524beta-lactams 522–537betamethasone 478betamipron 162betaxolol 39, 93, 325bethanidine 128betrixaban 367bevantolol 276, 327bevirimat 491bexarotene 509bezafibrate 154bezitramide 239BG 9928 442biapenem 524BIBW 2992 373bicalutamide 170, 184bicifadine 270bidisomide 238bifemelane 260bifeprunox 245biguanides 122, 123bilastine 155, 256biliary excretion 15bilobalide 95bimatoprost 540bioactivation, carcinogens 45, 133, 135bioavailability 6, 14bioisosteres– of carboxylic acids 146– of esters 393– of phenols 83– of thioethers 100biological stains, see dyesbiopterin 408biotin 162biperiden 233bisacodyl 207bisaramil 224Bischler–Napieralski reaction 269bis(2-chloroethyl)sulfide 54bisnorbiotin 162bisoprolol 325bisphenol A 86bisphosphonates 210–212

Index 575

bisquaternary ammonium salts 118, 119bizelesin 300Black, James 320bleeding, see anticoagulantsblonanserin 250blood clearance 7blood–brain barrier 16BMS-184476 555BMS-204352 200BMS-214662 476BMS-275183 555BMS-317180 356BMS-564929 179BMS-708163 353boceprevir 351BOF-4272 445bone resorbtion inhibitors 210–212bopindolol 324boronic acids 354, 355bortezomib 354bosentan 407Bossert, Friedrich 446bosutinib 374, 412bradycardics 263bradykinin B2 antagonists 359B-raf inhibitors 370brasofensine 251breathing, see respiratory stimulantsbrequinar 154, 521bretylium 117, 118brimonidine 126brinzolamide 457british anti-Lewisite (dimercaprol) 98brivanib 372brivanib alaninate 372brivaracetam 173, 175brivudine 53, 433brodimoprim 404brofaromine 259bromazepam 394, 469bromazine 235, 393bromfenac 500bromhexine 53, 116bromide 173bromine 53bromisovalum 193, 195bromoarenes 53bromobenzene 59bromocriptine 296bromodiphenhydramine 235bromopride 217bromotetrandrine 290bromovinyluracil 433bromperidol 241

brompheniramine 231bronchodilators– ammonium salts 222– PDE4 inhibitors 170– phenethylamines 280, 281, 283–286– xanthines 440–442brostallicin 357brotizolam 475Brotzu, Giuseppe 523bucolome 197budesonide 480budiodarone 261budipine 257buflomedil 242buformin 131bufuralol 286bumetanide 454, 508bunazosin 426bupivacaine 344bupranolol 39, 321buprenorphine 334bupropion 281burimamide 101buserelin 347, 357buspirone 249Buss, Carl Emil 497busulfan 55, 206butabarbital 199butalbital 198butanethiol 98butanol 98butaperazine 307butenafine 116butethal 199buthionine sulfoximine 157butofilolol 325butorphanol 331butriptyline 313tert-butylamine, pKa 110butylmercaptan 98butylscopolamine 222butylscopolammonium 118, 222O-benzoylmepindolol 324γ-butyrolactams 173–176butyrophenones 241, 242, 256

ccabazitaxel 555cabergoline 295cadralazine 187, 404caffeine 440, 451calcifediol 488calcipotriol 489calcitriol 488, 489

576 Index

calcium channel blockers– arylalkylamines 227, 229, 276, 277, 279– dihydropyridines 446–449– piperazines 241, 253, 345calcium disodium edetate 158calcium mimetics (agonists) 229calcium regulators 212, 488calcium sensitizers 411calomel (Hg2Cl2) 451camazepam 472Camptotheca acuminata 415camptothecin 415cancer, see antineoplasticscandesartan 546candesartan cilexetil 186, 546canertinib 374cannabinoid antagonists 171, 234canrenone 488capecitabine 187, 432capillary protectants, see vasoprotectantscapravirine 190capreomycin 1A 564capromorelin 356captopril 99, 162, 167, 335, 336, 339carazolol 326carbamates 187–191carbamazepine 17, 310, 316carbamazepine-10,11-epoxide 310, 316(2-carbamoylphenoxy)acetic acid 512carbamoyl phosphate I synthase activators

150carbapenems 523, 529–537carbenicillin 204, 528, 529carbetapentane 221carbidopa 83, 137, 159carbimazole 181, 201carbinoxamine 235, 393carbocromen 278carbohydrates 71, 78–81carbonates 186carbonic anhydrase inhibitors 385, 451, 454,

457, 458carboplatin 158N-(carboxyalkyl)-α-amino acid amides

335–340carboxylic acids 144–163– bioisosteres 146– metabolism 145carboxylic esters 154, 155, 164carboxypeptidases 166carbromal 193, 195carbutamide 462carcinogens 47, 49, 64, 68, 69, 117, 133, 178,

179, 183, 394

carcinoid syndrom 360cardiac arrhythmias 17cardiac depressants, see antiarrhythmicscardiac glycosides 81cardiac myosin activators 372cardioprotectives 130, 131, 196, 428cardiotonics 182, 276, 324, 400, 406, 410,

411, 425, 487cardiovascular agents 278carebastine 256carfecillin 529carfilzomib 352carglumic acid 150carindacillin 529Carini, David J. 543cariporide 130carisbamate 190carisoprodol 189carmegliptin 288, 342carmofur 434carmoxirole 248carmustine 69carnitine 161carnitine palmitoyltransferase inhibitors 230caroverine 227carprofen 501carteolol 323carticaine 344carumonam 534carvedilol 326casopitant 192, 266caspofungin 359catecholamines 83, 267, 268catechol-O-methyltransferase (COMT) 82,

83, 268catechols (1,2-dihydroxybenzenes) 82, 268cathartics, see laxativescathepsin K inhibitors 353caustics (keratolytics) 148Caventou, Joseph Bienaime 413CB 10-277 65, 507CCK antagonists 355CCR5 (chemokine 5) antagonists 253, 382CDK inhibitors 444cediranib 373cefaclor 530cefadroxil 530cefamandole 530cefatrizine 530cefazedone 532cefazolin 532cefcanel daloxate 186, 532cefdinir 533cefditoren pivoxil 535

Index 577

cefepime 535cefetamet 535cefetamet pivoxil 535cefixime 534cefmenoxime 536cefmetazole 532cefminox 533cefodizime 534cefonicid 203, 531cefoperazone 536ceforanide 531cefotaxime 534cefotetan 533cefotiam 536cefoxitin 531cefpimizole 537cefpiramide 536cefpirome 534cefpodoxime proxetil 186, 535cefprozil 530cefroxadine 530cefsulodin 532ceftaroline fosamil 532ceftazidime 534ceftibuten 102, 533ceftizoxime 533ceftobiprole medocaril 537ceftriaxone 536cefuroxime axetil 535celecoxib 455celiprolol 324centchroman 262central nervous system, see CNScephacetrile 531cephalexin 529cephaloridine 531cephalosporins 523, 529–537cephalosporin C 523cephalothin 531cephapirin 531cephradine 529cerivastatin 550ceronapril 209, 339cetamolol 322cetirizine 254cetrorelix 358cevimeline 264CGRP antagonists 354Chain, Ernst Boris 522chelating agents 158, 159, 398, 417, 508α-chemokine antagonists 565chemokine 5 (CCR5) antagonists 253, 382chemotherapeutics, see antineoplasticschinchona bark 4, 413

chloral hydrate 74, 138, 188chlorambucil 52, 56, 151chloramphenicol 60, 73, 78chlorcyclizine 252chlordiazepoxide 466, 467, 474chlorguanide 131chlorhexidine 124, 132chlorinated biphenyls 52chlorine 51chlorine vs methyl 52chlormadinone 482chlormequat 51chlormerodrin 451chlormethine 55chlormezanone 106, 1992-chloroethylamine derivatives 52chloromethyl ethers 49p-chlorophenoxyisobutyric acid (CPIB) 1541-(3-chlorophenyl)piperazine 247, 250chloroprocaine 216chloroquine 4, 113, 413, 414, 420chlorothiazide 451, 452chlorozotocin 69chlorphenesin 76chlorpheniramine 4, 71, 231chlorphentermine 272chlorproguanil 124, 131chlorpromazine 4, 109, 301, 304chlorpropamide 52, 463chlorprothixene 101, 305chlorquinaldol 417chlortetracycline 492, 494chlorthalidone 454chlorzoxazone 200cholecystokinin antagonists 150choleretics (bile excretion enhancers) 77cholesterol 548cholesteryl ester transfer inhibitors 177, 191choline 118cholinergics 85, 118, 190, 191, 264, 399, 420cholinesterase, see acetylcholinesterasechoriocarcinoma 551chromonar (carbocromen) 278CI 941 496cibenzoline 125cicaprost 539ciclazindol 125ciclesonide 480cicletanine 403ciclopirox 406cidofovir 209, 430cifenline 120, 125cilansetron 381cilastatin 160, 525

578 Index

cilazapril 339cilnidipine 448cilomilast 151cilostazol 247cimaterol 286cimetidine 17, 101, 377, 381cimetropium 222cimicoxib 455cimoxatone 176cinacalcet 48, 229cinaldipine 448cinchonine 422, 521cinchophen 153cinitapride 219cinmetacin 503cinnarizine 50, 253cinolazepam 474cinoxacin 515cipemastat 352ciprofibrate 144, 154ciprofloxacin 17, 514, 517ciramadol 73, 276cisapride 220, 246cisplatin 158citalopram 184, 234citrulline 157cizolirtine 235cladribine 436clamikalant 463clarithromycin 17, 559classic antihistaminics 225; see also

histamine H1 antagonistsclavulanic acid 524clearance 7clebopride 219clemastine 92, 236clenbuterol 35, 83, 286clentiazem 473clevidipine 448clinafloxacin 520clindamycin 78, 102clinical development 5clioquinol 417clobazam 474clobutinol 281clocapramine 168, 240, 314clodronic acid 212clofarabine 50, 436clofazimine 417clofibrate 154clofoctol 87clomethiazole 51, 57clomiphene 262clomipramine 314

clonazepam 468clonidine 123, 126clonixin 506clopamide 137, 453clopenthixol 308cloperastine 235clopidogrel 265cloprednol 479clorazepic acid 472clot prevention, see anticoagulants,

antithromboticsclotiazepam 475clotrimazole 387, 388cloxacillin 528cloxazolam 473clozapine 19, 318CMN 131 396CMX001 430CNDAC 432CNS stimulants– amidines 125, 128– benzhydrylamines 313– indoles 299– indolones 403– phenethylamines 251, 270, 271– sulfoxides 157– xanthines 440coagulation factors, see factor Xa inhibitorscocaethylene 224cocaine 215, 224cocaine addiction 241codeine 91, 108, 269, 332coffee 397, 398; see also caffeineCOL-3 495colchicine 476colorectal cancer; see antineoplasticscommon cold 225compactin (mevastatin) 548COMT inhibitors 83, 85, 86congestive heart failure 275, 411conivaptan 376conjugation reactions (phase II reactions)

15constipation 329; see also laxativescontergan 189contraceptives 262, 481–486, 490contrast agents 72, 75, 76coronary artery disease 548coronary vasodilators, see vasodilatorscorticosteroids 477–481cortisol 479cortisol biosynthesis inhibitors 196cortisone 477, 479cotinine 175, 395, 402

Index 579

cough suppressants, see antiussivescoumarin 141COX inhibitors 455, 498CP 14304 460CPI-1189 217CPIB 154creatine 127, 394creatinine 127, 394cremophor EL 554crizotinib 369cromakalim 3, 174cromoglicic acid 510cromolyn 510CS-758 389curare 289curcumin 89cyamemazine 305cyanide 184cyanoguanidines 202, 400cyclacillin 526cyclamate 37, 115, 205, 208cyclic peptides 347, 358–361, 563, 564cyclin-dependent kinase inhibitors 258cyclizine 226, 252cyclobarbital 197cyclobenzaprine 311cyclofenil 87cycloguanil 405cycloheptane 100cyclohexane 1001,2-cyclohexanediol 1411,4-cyclohexanediol 141cyclohexanes 37cyclohexanol 141cyclohexanone 141cyclohexylamine 115cyclooxygenase (COX) 538cyclooxygenase inhibitors 455, 456,

497–513cyclopentane 91, 100cyclophosphamide 52, 55cyclopropylamine, pKa 110cyclopropylmethyl group 39, 93cycloserine 160cyclosporine 358CYP-inhibition/induction 16, 17, 394,

395cyproheptadine 254, 314, 393cyproterone acetate 481cysteine 162cystemustine 69cystic fibrosis 508cytarabine 432

cytochrome P450, see CYPcytotoxic drugs, see antineoplastics

dDA-8159 443dabigatran etexilate 121, 363dacarbazine 65, 382daidzein 88dalfampridine 398dalfopristin 563daltroban 156danazol 485dantrolene 108, 183danusertib 368dapagliflozin 79dapiprazole 246dapotum 308dapoxetine 48, 228dapsone 87, 134darbufelone 85darexaban 367darifenacin 238, 278darinaparsin 355darodipine 448darunavir 352dasatinib 369daunorubicin 492, 493DDT 52dealkylation– of amides 169– of amines 110–114– of ethers 92– of lanosterol 387debrisoquin 128decitabine 430decongestants 124, 126, 280, 282DEET 169deferasirox 508deferiprone 398deferoxamine 357deflazacort 481dehalogenation 53dehydrogenase inhibitors 194deiodination 53delapril 338delavirdine 294, 425demeclocycline 494dementia 2174-demethoxydaunorubicin 493demexiptiline 313demoxepam 467, 474denaverine 165, 2212-deoxy-2-methylenecytidine 4312′-deoxyguanosine 437

580 Index

deprenyl 271deramciclane 234N-desalkylflurazepam 469des-ciclesonide 480desethylchloroquine 113, 414desferrioxamine 357desglymidodrine 167, 285desipramine 112, 114, 134, 311desloratadine 114, 255, 315, 393desmethylfluoxetine 112, 228N-desmethylimatinib 112, 396desmethylsibutramine 112O-desmethylvenlafaxine 276desmopressin 360desogestrel 140, 484desoxypipradrol 229detergents (disinfectants) 82, 87, 118detoxification 18development of drugs 13dexamethasone 17, 50, 478dexmedetomidine 378, 379dexrazoxane 172, 196dextromethorphan 331dextromoramide 237dextrorphanol 331dezocine 274DG-051 260diabetes, see antidiabeticsdiabetic neuropathy 163, 178diabetic retinopathy 375diacerein 89, 495, 513diacetolol 324diacetylmorphine 333diacetylrhein 89, 495, 513diagnostic aids 401, 508diagnostic dyes, see dyesdiamines 109, 1192,4-diaminoanisol 1333,4-diaminopyridine 398diaphoretics (sweating inducers) 380diazepam 93, 169, 468, 471diazepinomicin 317diazomethane 64diazonium salts 64diazoxide 452dibekacin 80dibenzazepines 310–317dibenzepin 317dibromoanthranilic acid 1171,2-dibromoethane 49dichloroacetic acid 148dichlorobenzene 592,6-dichlorobenzaldehyde 1302,6-dichlorobenzylalcohol 130

2,6-dichlorophenol 126dichlorphenamide 454dichlorvos 74diclofenac 47, 505dicloxacillin 528dicoumarol 143dicyclomine 221dicycloverine 221didanosine 435dienogest 184, 486diet, see anorexicsdiethylamine, pKa 1105,5-diethylbarbituric acid 193diethylcarbamazine 192, 194diethylcathinone 270diethylpropion 270diethylstilbestrol 87diethylthiomethylcarbamate 194difenoxin 239diflomotecan 424difloxacin 517diflunisal 513difluorodeoxyuridine 431difluoroethylamine, pKa 110digitalis 81digitoxin 81, 451digoxin 81dihydroazacytidine 430dihydrobiopterin 408dihydrocodeine 332dihydroergocristine 296dihydroergocryptine 296dihydroergotamine 296dihydroergotoxine 297dihydrofolate reductase inhibitors 408, 409,

551–553dihydroorotate dehydrogenase inhibitors 20,

169dihydropyridines 60, 446–449dihydrotachysterol 488dihydroxybenzenes 82, 831,2-dihydroxycyclohexane 141diloxanide furoate 85Dilthey, Alfred 193diltiazem 17, 165, 446, 474dimercaprol (British anti-Lewisite,

2,3-dimercaptopropanol) 98dimethadione 177dimethindene 2324-dimethylaminoazobenzene 133dimethylamino group 109–1124-dimethylaminostilbene 1332,6-dimethylaniline 341, 343dimethylcysteine 99, 159, 339

Index 581

dimethylether 100dimethyl fumarate 149dimethylnitrosoadamantane 115N-(2,6-dimethylphenyl)glycinamides 341dimethylsulfide 100dinoprostone 539dioxin (tetrachlorodioxin) 52dipeptidylpeptidase IV, see also DPPIVdiphenhydramine 17, 225, 234, 377diphenoxylate 239diphenylpyraline 257dipipanone 237(S)-diprafenone 325diprophylline 441dipropyl ether 91dipyrone 181, 203dirithromycin 561discovery of drugs 3disinfectants 82, 87, 118disobutamide 108, 238disopyramide 108, 238dispersion (London) forces 51disposition of drugs 15distigmine 399distribution, volume of 6disulfiram 194, 202ditazol 75diuretics– aldosterone antagonists 487, 488– loop 131, 155, 161, 181, 385– mercurial 451– sodium channel blockers 130, 408– sulfonamides 450, 452–455, 457, 463– osmotic 76, 77, 193– other 230, 441DJ-927 556DMDC 431DMSO 101DMXAA 505DNA gyrase 514DNA gyrase inhibitors 8, 514DNA ligands 357DNA methylation inhibitors 429dobutamine 276docetaxel 554dofetilide 279dolasetron 223Domagk, Gerhard 62, 450domperidone 244donepezil 139, 245L-dopa, see levodopadopamine 267, 268dopamine agonists 250, 272, 275, 296

dopamine antagonists 217, 240–242, 244,245, 260

dopamine DA2 agonists 248dopamine D2 agonists 274, 275dopamine D2 antagonists 217–219, 240,

250dopamine D3 antagonists 27, 218dopamine D4 antagonists 246dopamine reuptake inhibitors 241, 251, 281,

516dopamine transport blockers 230dopamine–norepinephrine reuptake

inhibitors 281dopamine receptors 225dopexamine 276doranidazole 383doripenem 524dorzolamide 457dosulepin 313dothiepin 101, 313doxacurium 289doxapram 234doxazosin 425doxefazepam 474doxepin 101, 145, 312doxercalciferol 489doxofylline 138, 441doxorubicin 492doxycycline 493doxylamine 92, 235DPPIV inhibitors 8, 23, 273, 288, 342, 345,

346, 355, 435, 443droloxifene 263dronabinol 86dronedarone 261droperidol 242drospirenone 488drotaverine 287drug development 3drug discovery 3drug–drug interactions 16drug excipients 77DTI-0009 438duloxetine 228Duncia, John V. 543DuP 697 456DuPont 543dutasteride 487dydrogesterone 482dyes 62, 89, 90, 300, 495, 508, 512dyes, as antibacterials 62, 512dynorphins 329dyphylline 441dyskinesia (tremor) 217, 287, 401

582 Index

eE-2020 245EAA 090 211ebastine 256ebrotidine 132ecstasy 275edatrexate 552edotecarin 375edoxaban 367edrophonium 85EDTA 158EF5 384efaproxiral 154efavirenz 17, 188, 200efegatran 364eflornithine 157EHNA 444Ehrlich, Paul 62eicosanoids 538elcometrine 481electron-poor alkenes (Michael acceptors)

19, 155electrophilic metabolites 17–19elesclomol 194eletriptan 293elgodipine 449eliglustat 279elimination of drugs 15elinogrel 465eliprodil 283eltanolone 483eltoprazine 134, 250eltrombopag 140, 153elvitegravir 516elvucitabine 433EMD 87580 106, 123, 130emedastine 258emepronium 230emetics 287emtricitabine 138, 431enalapril 335, 336enalkiren 357encainide 220enclomiphene 262endopeptidases 166endorphins 329endothelin antagonists 151, 369, 407, 408,

458, 509endralazine 137, 419enilconazole 388eniporide 130enkephalins 329enocitabine 432enoltasosartan 546, 547

enoxacin 17, 517enoximone 182enprofylline 440ensaculin 247entacapone 83, 86entecavir 73, 437enterohepatic recirculation 15entinostat 136, 188, 366enzastaurin 375enzymatic activation 18, 19epalrestat 153, 201epanolol 327eperisone 242ephedrine 280epichlorohydrin 49epinastine 316epinephrine (adrenaline) 3, 267epirubicin 492eplerenone 96, 488eplivanserin 236epothilone B 564epoxide hydrolase inhibitors 28epoxides 96epristeride 487eprodisate 203, 204eprosartan 545eptastigmine 191erdosteine 162Erdtman, Holger 341erectile dysfunction 299, 442, 443, 539ergocalciferol 488ergocristine, see dihydroergocristineergoloid 297ergosterol 387ergot alkaloids 291, 296, 297ergotamine 296erlotinib 44, 374, 415ertapenem 525erythrohydroxynonyladenine 444erythromycin 17, 108, 557, 560eslicarbazepine acetate 316esmolol 326esophageal reflux, see antiulcerativesestazolam 470esters 154, 155, 164estradiol 44, 477, 486estramustine 56estriol 486estrogen receptor modulators 260–262estrogens 87, 477, 485, 486estrone 486ET-743 288etafenoxine 125etamiphylline 442

Index 583

etamsylate 203, 205etanidazole 383ethacrynic acid 155, 451ethambutol 116ethanol 17, 71, 74ethanolamine, pKa 110ethchlorvynol 44, 74ethers 91ethinamate 443′-C-ethinylcytidine 431ethinyl estradiol 44, 82, 485ethinyl estradiol-3-sulfate 485ethinyl estradiol-17-sulfate 485ethionamide 201, 400ethopropazine 303ethosuximide 172, 177ethoxybenzene 91ethoxybenzenes 91, 92ethoxzolamide 385, 457ethylamphetamine 270N-(2-ethylbutanoyl)urea 193ethyl carbamate 188ethylenediamine 110, 116ethylene glycol 76ethylenimines (aziridines) 54ethyl ethers 91ethylphenylmalonamide 196etidocaine 343etidronic acid 212etifoxine 125etilefrin 282etintidine 382etizolam 475etodolac 501etofenamate 506etofylline 440etomidate 380etonogestrel 140, 484etoperidone 247etoposide 89etoricoxib 106, 403, 456etozolin 161etravirine 184, 405etretinate 153β-eucaine 215everolimus 559exatecan 424excipients 77excitatory amino acids, see AMPA, GABA,

NMDAexcretion of drugs 14, 15exemestane 486exopeptidases 166EXP 3174 545

EXP 6155 544EXP 6803 544EXP 7711 544expectorants 76, 116, 117; see also

mucolyticsezetimibe 86ezogabine 404

fFabry disease 279factor Xa inhibitors 170, 176, 177, 266, 363,

367, 370fadrozole 390falipamil 276famciclovir 443famotidine 122, 132fampridine 398fantofarone 277Farber, Sidney 551farnesyltransferase inhibitors 255, 380, 476faropenem 524fasudil 422fatigue suppression 268fazadinium 410fazarabine 430FDA 9, 10febuprol 73, 77febuxostat 510felbamate 17, 19, 20, 188, 189felodipine 60, 108, 447femoxetine 251fenbufen 150fenclofenac 47, 505fenclozic acid 504fendiline 229fendosal 513fenethazine 301fenfluramine 271fenofibrate 155fenoldopam 272fenoprofen 501fenoterol 284fenpiprane 71, 232fenproporex 271fenquizone 453fenspiride 188, 243fentanyl 243fentiazac 504feprazone 180fesoterodine 232fever, see NSAIDsfexinidazole 384fexofenadine 256fiacitabine 431

584 Index

fialuridine 431, 433fibrates 144, 154, 155, 548fibrin 349fibrinogen 349fibrinogen antagonists 361fidarestat 178fidaxomicin 562fiduxosin 278Filehne, Wilhelm 173finasteride 487fingolimod 73, 77finrozole 390first-pass metabolism 14, 15Fischer, Emil 193Fischer, Otto 172five-membered lactams 173–176FK506 559FK-binding protein 557flavopiridol 252flavoxate 88, 164flecainide 220Fleming, Alexander 522fleroxacin 518flesinoxan 245flestolol 195flomoxef 533Florey, Howard 522flosequinan 418, 515flosulide 455flovagatran 355floxacillin 528flucloxacillin 528fluconazole 17, 213, 389flucytosine 434fludarabine 436fludiazepam 60, 93, 469flufenamic acid 394, 507fluindione 142flumazenil 471flumezinol 74flumequine 515flunarizine 41, 50, 253flunisolide 480flunitrazepam 60, 468flunoxaprofen 501fluocinolone acetonide 480fluocortolone 481fluorescein 508fluorine 492-fluoroaniline 492-fluorophenol 491-(4-fluorophenyl)piperazine 2505-fluorouracil 434fluoxetine 10, 17, 112, 228

fluoxymesterone 485flupentixol 309fluphenazine 308flupirtine 188, 394, 404flurazepam 469, 474flurbiprofen 499flurithromycin 560flusoxolol 325flutamide 170fluticasone 50, 481flutoprazepam 93, 469fluvastatin 17, 549fluvoxamine 17, 140, 236, 272folic acid analogs 551–553folinic acid 552fomepizole 379, 388fominoben 345formamides 356formestane 487formoterol 2834-(formylamino)antipyrine 181forodesine 437fosamprenavir 214, 351fosaprepitant 214foscarnet 209, 210fosfluconazole 213, 390fosfomycin 209, 210fosinopril 339fosmidomycin 209, 211fosphenytoin 179, 213fospropofol 84fostamatinib 366fostriecin 214fotemustine 69fradafiban 362Franke, Hans 462frovatriptan 293Fuchs, Joachim 462fulvestrant 486fungal infections, see antifungalsfungicides 86furafylline 441Furakawa, Y. 543furegrelate 510furosemide 454, 508fusidic acid 152, 491future of small molecule drugs 9

gGABA agonists 149, 160, 161, 204, 391GABA receptor modulators 483GABA reuptake inhibitors 240gabapentin 37, 160gaboxadol 161, 264

Index 585

galantamine 334gallamine 259gallopamil 277ganaxolone 483ganciclovir 437ganglionic blocking agents 118Gardos channel inhibitors 151garenoxacin 521gastric ulcers, see antiulcerativesgastrin project 396gastrointestinal tract 14gastroprokinetics 217–220, 246, 355gastroprotectants 141, 541gatifloxacin 518Gaucher’s disease 78, 279gefitinib 373, 412gemcitabine 73, 431gemfibrozil 154, 550gemifloxacin 520genaconazole 389genistein 88gentamicin 80gentisamide 512gentisic acid 511gepefrine 273gepirone 249gestodene 484gimatecan 423glaucoma 122, 126glibenclamide 464glibornuride 463gliclazide 463glimepiride 464glipizide 464gliquidone 464glisoxepid 464GLP-1 342glucocorticoids 477–481glucose transporter inhibitors 79glucosylceramide synthase inhibitors 279glucuronidation 15, 146glutarimides 172, 195, 196glutathione 15, 157glutathione transferases 15glutethimide 172, 196glyburide 464glycerin dinitrate 66glycerol 71, 76glycine, as solubility enhancer 114, 166glycine ethyl ester, pKa 110glycol 76glycopyrrolate 221glycosides– anthracycline 492, 493

– antibacterial 78–81– cardiac 81glymidine 458GnRH agonists 357, 358GnRH antagonists 358gold sodium thiomalate 158gonadotropin agonists 347goserelin 358gout suppressants 476, 510gramine 341granisetron 223grapefruit 16, 17grepafloxacin 17, 517growth hormone 17growth hormone secretagogues 356Grunenthal 189guaifenesin 76guanabenz 122, 130guanadrel 128, 140guanethidine 122, 128guanfacine 123, 130, 342guanidine 127guanidines 122guanoxan 128guanylate cyclase stimulators 370gut 14GW597599 265gyrase inhibitors 514

hhaemo-, see hemo-halazepam 169, 470half-life of drugs 6, 15halides 49hallucinogenics 116, 264, 275, 295haloalkanes 49halofantrine 113, 233halofenate 155halofenic acid 155haloperidol 17, 72, 139, 241halothane 53hay fever 225–227, 252–258; see also

antipruritics, histamine H1 antagonistsheadache, see migraine, antimigraine agentsheart failure 372, 509heart valve damage 271heat shock protein 8heavy-metal poisoning, antidotes for 158,

159, 162hedgehog signaling inhibitors 366hedonal 193helminths (worms), see anthelminticshemiacetals 92, 138hemoglobin 133, 138, 154, 509

586 Index

hemolytic anemia 133, 517hemorheologic agents 441hemorraghe, see anticoagulantshemostatics 148, 157, 160, 182, 205heparin 349hepatic enzyme inducers 74hepatitis 351, 436hepatitis C virus protease inhibitors 351hepatoprotectants 159, 162hepatotoxicity 18heptabarbital 197heptane 91herbicides 84, 142, 155, 397, 402hERG 17heroin 164, 333Hertz, Roy 551hexachlorocyclohexane (lindane) 56hexachlorophene 87hexanols, solubility 36hexobarbital 41, 197hippuric acid 145, 511histamine 107, 377, 379, 393histamine agonists 377, 379, 401histamine antagonists 377histamine H1 antagonists 155, 225, 227,

230–232, 234–236, 239, 248, 252–258, 303,304, 312, 316, 402, 442

histamine H2 antagonists 101, 132, 264,377, 380–382, 402

histamine H3 antagonists 377histamine H4 antagonists 377histamine receptors 225histidine 377histone deacetylase inhibitors 156, 360, 366,

367HIV integrase inhibitors 26, 516HIV protease inhibitors 25, 350–352, 354;

see also antiviralsHIV-1 maturation inhibitors 491HMG CoA reductase inhibitors 548–550Hodkin, Dorothy Crowfoot 522Hoechst 173, 215Hoffmann, Felix 498Hoffmann-La Roche 466homotaurine 204hormone replacement therapy 477, 484HSP70 inducers 194HSP90 inhibitors 8human ether-a-go-go related gene 17hycanthone 496hydantoins 178, 179, 183hydralazine 137, 419hydrazines 137hydrazones 137

hydrocephalus 94hydrochlorothiazide 452hydrocodone 91, 92, 332hydrocortisone 479hydroflumethiazide 452hydromorphone 91, 92, 331hydrophilic pores 14, 119hydrophilicity, effect on PK 6, 7, 71, 72hydroxamic acids 146, 147, 156, 157, 352,

353hydroxy acids 157N-hydroxyamidines 120, 1214-hydroxybutyric acid 14910-hydroxycarbamazepine 316hydroxychloroquine 4201-hydroxycholecalciferol 4893-hydroxycotinine 176, 4023-hydroxydihydroquinidine 422hydroxyethylmorphine 3325-hydroxyindoles 159hydroxyindolylacetic acid 1593-hydroxyquinidine 42hydroxylamines 133, 1355-hydroxymethyltolterodine 232hydroxynortriptyline 312hydroxytriamterene sulfate 4082-hydroxy-4-trifluoromethylbenzoic acid 511hydroxytrimazosin 735-hydroxytryptamine (5-HT), see serotonin5-hydroxytryptophan 159hydroxyurea 192, 1941α-hydroxyvitamin D2 489hydroxyzine 254hyoscyamine (atropine) 223hyperammonemia 149, 150hypercalcemia 212hypercholesterolemia 548hypericin 90hyperprolactinemia 274, 294–296hypertension 543; see also antihypertensiveshyperuricemia 445hypnotics– acyclic ureides 193, 195– alcohols 74– amides 288, 371, 410, 426, 427– barbiturates 193, 197–199– benzodiazepines 466–476– carbamates 188, 189– other 74, 161, 235, 236, 380– phenothiazines 303, 305– piperidinediones 195, 196, 199hypoglycemia 452hypolipidemics 87hyponatremia 376

Index 587

hypotensives, see antihypertensiveshypoxanthine 435hypoxia probes 384hypoxia-selective antineoplastics 419

iibandronic acid 211ibudilast 440ibuprofen 497, 498ibuproxam 498ibutilide 285ICA-17043 151icatibant 359ICI 320ICL 670 508iclaprim 405icofungipen 160idarubicin 493idarubicinol 493idazoxan 125idebenone 141idoxuridine 433idrapril 352idrocilamide 75idronoxil 89ifenprodil 283ifetroban 156ifosfamide 55I. G. Farben 450ilaprazole 410iloperidone 245iloprost 540imatinib 112, 368imidafenacin 237, 380imidapril 337imidazole 377, 379imidazoles 377–386imidazolines 120imides 146, 172imipenem 525imipramine 101, 112, 310, 311imipramine N-oxide 112, 311imiquimod 418immunogenicity 347, 523immunomodulators 77, 169, 174, 196, 418,

436, 439, 559immunostimulants 565immunosuppressants 55, 153, 154, 358,

403, 428, 439, 496, 557–559incadronic acid 211INCB 9471 253incontinence 220, 232, 238indacaterol 283indalpine 259

indanazoline 126indapamide 453indecainide 238indeloxazine 280, 322indinavir 17, 349, 350indiplon 371indirectly acting sympathomimetics 268indobufen 500indocyanine green 300indole alkaloids 291–300indomethacin 146, 502indoprofen 499indoramin 244induction of CYP 16infertility 477inflammation, see antiinflammatoriesinhibition of CYP 16injection (parenteral dosing) of drugs 15–17inogatran 364inosine 435inotropics, see cardiotonicsinsect repellents 169insecticides 56, 84, 457in silico drug discovery 9insulin secretagogues 129insulin sensitizers 151, 152, 178, 179interactions, drug–drug 16intercalators 492, 496intestine 14intoplicine 299intoxication 17–20intraocular pressure 126; see also

antiglaucoma agentsiodine 53iodixanol 75iodoquinol 54, 417iohexol 54, 75iomeprol 75iopamidol 72, 76iopromide 75iosimide 76ipratropium 222ipriflavone 88iprindole 236iproniazid 137, 400ipsapirone 249irbesartan 38, 545irinotecan 424irofulven 141iron chelators 357, 508irreversible tyrosine kinase inhibitors 374irritable bowel disease 217, 278, 281, 381irsogladine 407isatoribine 436

588 Index

isavuconazole 387, 388isepamicin 80isoamyl nitrite 66isobutyl nitrite 66isofagomine 78isofezolac 504isoflavones 88isogramine 341isomazole 410isoniazid 17, 137, 399isopropylamine, pKa 110isoproterenol 83, 284isoquinolines 269isosorbide 94isosorbide dinitrate 66, 93isosorbide mononitrate 66, 94isosteres, see bioisosteresisotretinoin 153isovaleramide 148isoxicam 460isoxsuprine 283ispinesib 374ispronicline 401isradipine 108, 448istaroxime 487istradefylline 442itasetron 223itching, see antipruriticsitraconazole 17, 140, 391ivabradine 277ivermectin 562ixabepilone 96, 564

jJendrassik, Ernst 451

kKA-672 247kairine 173kairoline A 173kanamycin B 80karenitecin 423keratolytics 148ketamine 281ketanserin 244ketazolam 473ketobemidone 330ketoconazole 17, 3913-ketodesogestrel 4842-ketodoxapram 234ketones 139ketoprofen 500ketorolac 503

ketotifen 255, 315kidneys 15kinase inhibitors 422, see also

antineoplasticskinesin spindle protein inhibitors 374Klarer, Josef 62, 450Knorr, Ludwig 173Koenigs, Wilhelm 172Kolbe, Adolph Wilhelm Hermann 497Koller, Carl 215KRN-5500 444Kuhn, Roland 310Kurzrok, Raphael 538KW-6002 442

llabetalol 285Laborit, Henri 301lacidipine 448lacosamide 354lactams 172–183β-lactams 522–537lactic acidosis 131lactones 165, 559–562, 564lactulose 78lafutidine 402lamifiban 361lamivudine 431lamotrigine 405landiolol 327laninamivir 129lanosterol 387lanreotide 360lansoprazole 409lapatinib 374laquinimod 461laropiprant 144, 505lasofoxifene 111, 262latamoxef 533latanoprost 541laxatives 77, 78, 130, 207, 264, 539lazabemide 401LBM 415 356lead discovery 3–8lead optimization 13–20lecozotan 245leflunomide 169lefradafiban 187, 362lenalidomide 172, 196lenampicillin 526leprostatics 87lercanidipine 448lesopitron 249letrozole 184, 390

Index 589

leucovorin 552leukemia 206, 493, 509, 551leukotriene A4 hydrolase inhibitor 260leukotriene D4 antagonists 423, 511leukotrienes 538leuprorelin 358levallorphan 331levamisole 127levetiracetam 168, 173, 175levobunolol 47, 321, 323levocabastine 239levodopa 83, 159levodropropizine 248levofloxacin 519levomepromazine 305levomethorphan 331levonorgestrel 483, 484levoprotiline 306levorphanol 331levosimendan 411levovirin 429librium 466licofelone 504lidocaine 215, 341, 342, 343lidoflazine 241, 345Lieb, Charles 538Liebreich, Oscar 188lignocaine 343linagliptin 41, 111, 342, 443lincomycin 78lindane 56linezolid 176linifanib 371linopirdine 403lipase inhibitors 152lipid peroxidation inhibitors 490lipid-lowering drugs, see antilipemics5-lipoxygenase inhibitors 194lirimilast 195lisinopril 336Lister, Joseph 82lisuride 192, 295litracene 306liver 13–19lixivaptan 376lobeline 263lobucavir 438local anesthetics 77, 84, 215, 216, 224, 236,

341–344, 483locomotor stimulants 516lofepramine 114, 311lofexidine 120, 126, 342lomefloxacin 518lometrexol 552

lomustine 68lonafarnib 255lonazolac 504London dispersion forces 51long QT syndrome 17lonidamine 502loop diuretics 131, 155, 161, 181, 385loperamide 241lopinavir 350loprazolam 475loracarbef 530loratadine 226, 255, 315lorazepam 473lorcainide 113, 257lorcaserin 272lormetazepam 472lornoxicam 460losartan 543–545losoxantrone 496lotrafiban 361lovastatin (mevinolin) 548, 549loxapine 19, 318loxiglumide 355loxoprofen 498LSD 295lubeluzole 246, 327lubiprostone 539lucanthone 496lumefantrine 233lumiracoxib 506lurasidone 249lurtotecan 424lusitropics 487LY-517717 266lymecycline 494lysergic acid diethylamide 295

mmabuterol 286macitentan 408macrocyclic compounds 557–565macrolides 557–564Maillard reaction 394malaria, see antiprotozoalsmanidipine 449mannitol 71, 77MAO inhibitors 117, 216, 259, 270, 271, 273,

293, 400, 401MAP kinase inhibitors 366maprotiline 306maraviroc 240marijuana, see THCmarimastat 353masitinib 368

590 Index

matrix metalloproteinase inhibitors 21, 26,352, 353, 495

maxipost 200mazindol 125MDMA 275mebendazole 385mechlorethamine 52, 55meclizine 252meclofenamic acid 506meclozine 252medazepam 471medifoxamine 138, 259medrogestone 483medroxalol 285medroxyprogesterone 482medroxyprogesterone acetate 482mefenamic acid 136, 506mefloquine 111, 414, 422mefruside 454megestrol acetate 482meglumine 77MEK inhibitors 372melagatran 362melanin-concentrating hormone receptor-1

antagonists 29melatonin 292melatonin MT1/MT2 agonists 275melitracene 306melogliptin 346meloxicam 460melperone 242melphalan 56, 151memantine 37, 115menogaril 493menopausal hot flushes 218menthol 74meobentine 128meperidine 251mephentermine 271mephobarbital 41, 197mepindolol 324mepivacaine 343meprobamate 189meptazinol 274mepyramine 227mequitazine 304merbaphen 451mercamphamide 451mercaptans 98mercaptoethanesulfonic acid (mesna) 99,

203, 205mercaptoimidazole (thiamazole) 182, 379mercaptomerin 451mercaptopurine 99, 439

mercaptovaline 99, 159, 339Merck & Co. 544mercumatilin 451mercurous chloride 451mercury-containing drugs 451meropenem 525mersalyl 451mesalazine 511mescaline 145, 275mesna 99, 203, 205mesotrione 142mestranol 485mesylates 206metabolic activation 17–19, 133metaclazepam 472metaldehyde 94metamizol 181metapramine 317metaproterenol 284metapyrilene 225, 227metaraminol 282metastat 495metaxalone 177metformin 124, 131methacycline 494methadone 139, 237methamphetamine 270methanesulfonic esters 206methaqualone 419methazolamide 457methdilazine 304methemoglobin 133methicillin 528methimazole 99, 182, 379methionine 159methitural 102methixene 304methocarbamol 190methohexital 41, 198methotrexate 147, 551methotrimeprazine 305methoxsalen 142methoxynaphthylacetic acid 1418-methoxypsoralen 1427-methoxytacrine 420methsuximide 1784-(methylamino)antipyrine 203methylaminorex 280methylanilines 341L-N-methylarginine 129, 157methyl benzoate 59methyldopa 159methylene blue 62

Index 591

3,4-methylenedioxymethamphetamine275

methylergometrine 295methylergonovine 295(R)-α-methylhistamine 379methylnaltrexone 334methylphenidate 251methylprednisolone 478N-methylpyridinium 3973-methyl-2-thiohydantoin 182methyprylon 199methysergide 295metiamide 101metipranolol 324metoclopramide 217metocurine 289metolazone 138, 453metopimazine 168, 308metoprolol 39, 93, 325metopyrone 401metrifonate 74metronidazole 17, 378, 383metyrapone 401mevalonate 548mevastatin (compactin) 548mevinolin (lovastatin) 548, 549mexazolam 473mexiletine 259, 342mezlocillin 527MGCD-0103 367mianserin 317, 394mibefradil 279micafungin 359Michael acceptors 19, 155miconazole 17, 387, 388microtubule-stabilizing agents 564midazolam 471midodrine 167, 285, 286Mietzsch, Fritz 62, 450mifentidine 380mifepristone 490miglitol 72, 77miglustat 78migraine 291migraine prophylaxis 255milnacipran 237milrinone 406minaprine 406mineralocorticoids, see corticosteroids,

steroidsminocycline 495minoxidil 70, 407miotics (contract pupil) 190, 380mirtazapine 317, 394

misonidazole 383misoprostol 538, 541mitiglinide 150mitomycin C 300mitotane 56mitoxantrone 496mivacurium 289mizolastine 258mizoribine 428MK-0974 354MK-473 155MKC-1 375MMI-270 353moclobemide 216modafinil 146, 157, 168moexipril 338mofarotene 262mofebutazone 180mofegiline 43molecular modeling 9, 10molecular weight 13–16molluscicides 94molsidomine 161mometasone 479monoamine oxidase (MAO) 267, 268monomethyl fumarate 149montelukast 422moprolol 322morclofone 261mordant yellow 512moricizine 17, 307morocromen 192, 278morphine 269, 329, 332morpholine, pKa 110mosapramine 240, 314mosapride 218motesanib 366motility, gastrointestinal, see

gastroprokineticsmotion sickness 222, 226moxalactam 533moxifloxacin 519moxonidine 123, 127MS-275 366mucolytics 98, 116, 162multidrug resistance gene 16multiple sclerosis 169, 398, 461muraglitazar 152, 188muscarinic acetylcholine M1 antagonists

313muscarinic acetylcholine M3 antagonists

238muscarinic agonists 264muscarinic antagonists 118, 222, 237

592 Index

muscle relaxants– skeletal 75, 115, 126, 160, 177, 183, 189,

190, 200, 234, 242, 259, 264, 300, 311,410, 419, 468

– smooth, see anticholinergics,bronchodilators, vasodilators

muscular dystrophy 508mushroom poisons 347mustards 52, 54–56muzolimine 131, 181, 379myalex 504mycophenolic acid 153mydriatics (enlarge pupil) 282, 299myoson 232

nnabilone 86nabumetone 139, 141nadolol 323nafamostat 127, 164nafarelin 358nafcillin 48, 526nafronyl 48, 221naftazone 182, 192naftidrofuryl 221naftopidil 248, 327nalbuphine 333nalidixic acid 514, 516nalmefene 333naloxone 333naltrexone 333naphazoline 48naphthalene 472-naphthylamine 133naphthyl groups 481-naphthyl N-methylcarbamate 481-naphthylthiourea 48naphthyridines 415, 416naproxen 499napsagatran 363naratriptan 258, 293narcotic antagonists 119, 239, 330, 331, 333narcotics, see analgesicsnaronapride 220nasal decongestants 124, 126, 280, 282nasal dosing, peptides 347nateglinide 38, 163National Cancer Institute 415, 554natriuresis enhancers 442nausea, see antiemetics, emeticsnaveglitazar 151navitoclax 365nebicapone 85nebivolol 327

nedocromil 509, 515nefazodone 17, 247nefiracetam 174, 344nefopam 235negamycin 161, 355nelarabine 438nelfinavir 351nematodes, see anthelminticsnemonapride 219nemonoxacin 519neopentylamine, pKa 110neoplastic diseases, see antineoplasticsneostigmine 118, 187, 190nepafenac 168, 500neramexane 111, 115neratinib 373netilmicin 81netobimin 61, 385neuraminidase inibitors 122, 129, 160neuritis 189neurokinin NK1 antagonists 265, 266neurokinin NK3 antagonists 418neuroleptics, see antipsychoticsneuromuscular blocking agents 118, 119,

289, 290, 300, 490, 491neuroprotectants 95, 211, 246, 249, 259, 283,

385nevirapine 17, 317nexopamil 277NF-κB activation inhibitors 149NHE-1 130niacin 398, 505, 548niaprazine 248nicainoprol 323nicardipine 449niclosamide 86nicorandil 66, 401nicotinamide 398, 399nicotine 393, 402nicotine addiction 272nicotinic acetylcholine agonists 118, 259,

401nicotinic acid 398nicotinic agonists 118, 272nicotinic receptors 118N-nicotinoyl glycine 398nicoumalone 143nifedipine 60, 447nifekalant 435niflumic acid 394, 507nifurtimox 183nikethamide 399nilotinib 368nilutamide 60, 179

Index 593

nilvadipine 447nimesulide 455nimetazepam 468nimodipine 447nimorazole 383nimustine 69nipradilol 323niridazole 183nisoldipine 447nitazoxanide 183nitisinone 142nitrates 66nitrazepam 60, 468nitrendipine 60, 447nitric oxide 66nitric oxide synthase inhibitors 128, 129, 157nitriles 184nitrites 66nitro compounds 59nitroarenes 59nitrobenzene 59nitrofurans 61, 183nitrofurantoin 60, 183nitrofurazone 183nitrogen mustards 52, 54–56nitroglycerin 66, 76nitroimidazoles 378nitroso compounds 68nitrosoarenes 60, 135nitrosoureas 54, 68nitrothiazoles 183nitrous oxide 161nizatidine 132NK, see neurokininNK-611 90NMDA antagonists 115, 211, 270, 281, 283,

427, 501noberastine 258nocloprost 541nolatrexed 418nolomirole 275nomifensine 136, 230nonsedating histamine H1 antagonists

256–258nonsense mutation suppressors 508nonsteroidal antiandrogens 170, 179nonsteroidal antiinflammatory drugs, see

NSAIDsnootropics– 3-(aryloxy)propylamines 246, 247, 260,

280– benzylamines 190– five-membered lactams 173–175– nicotine analogs 259, 264, 401

– other pyridines 403, 420– quinones 141– tryptamine derivatives 297, 298noradrenaline 267noradrenaline reuptake inhibitors 228, 270,

276noradrenaline/dopamine reuptake inhibitors

229norbutriptyline 313norchlorcyclizine 252norcyclizine 252nordazepam 60, 169, 394, 467, 469, 472norepinephrine reuptake inhibitors 228,

270, 276norethindrone 484norethisterone 484norfenefrine 281norfloxacin 514, 517norgestimate 483normeperidine 168nornicotine 402norpropoxyphene 229nortilidine 330nortriptyline 312norzimeldine 231noscapine 269, 288NSAIDs– arylacetic acids 497–506– arylpropionic acids 303, 497–503– benzoic acids 497, 498, 506, 507– other 75, 150, 224, 236, 403, 419, 455, 456– phenols 85– pyrazolones 180, 181– salicylates 497, 498, 511–513– thiazinecarboxamides 459, 460NTBC 142nucleoside analogs 428–445nucleoside phosphorylase inhibitors 439nufenoxole 237NXL-104 182, 207

oobatoclax 375obesity 152, 171; see also anorexicsobidoxime 399ocinaplon 370octofene 87octopamine 282octreotide 360odanacatib 353ofloxacin 514, 518oglemilast 400olanzapine 19, 318olaparib 372, 411

594 Index

olcegepant 354olefins 40–44oligoamides 347, 365oligoarylamines 365oligosaccharides 78–81olmesartan medoxomil 186, 545olopatadine 145, 312olpadronic acid 211olsalazine 62, 512omapatrilate 99, 339omecamtiv mecarbil 372omeprazole 10, 17, 104, 396, 409oncogenes, see carcinogensoncolytics, see antineoplasticsondansetron 381OPC-6535 508opiate agonists 239, 241, 243, 274, 329–334opiate antagonists 119, 239, 330, 331, 333opiates 329–334opioid analgesics, see analgesicsopipramol 311opium 269optimization of leads 13, 20oral bioavailability 6, 14orbofiban 362orciprenaline 83, 284orexin antagonists 288organomercurials 451orlistat 152ormeloxifen 262ornidazole 51, 383orotic acid 435orphenadrine 234ortataxel 556orthocaine new 215oseltamivir 160, 164osmotic agents 94osmotic diuretics 76, 77, 193osmotic laxatives 77, 78ospemifene 263ostarine 170osteoporosis 210, 260–263otamixaban 363overactive bladder 230, 281oxacillin 528oxaliplatin 158oxametacine 147, 502oxamniquine 287oxantel 124oxantrazole 496oxaprozin 144, 150oxatomide 254oxazepam 169, 467, 472oxazidione 142

oxazolam 473oxcarbazepine 316oxedrine 35, 282oxidative stress inducers 194N-oxides 70oximes 138oxiracetam 72, 175oxiranes 96oxisuran 105, 403oxitriptan 159, 292oxitropium 222oxmetidine 382oxolinic acid 515oxprenolol 322oxybate sodium 149oxybutynin 165, 221, 233oxycodone 333oxymetazoline 124oxyphenbutazone 180oxypurinol 439oxytetracycline 494oxytocics 295ozagrel 380ozolinon 161

pPA-824 384paclitaxel 554, 555pafenolol 326Paget’s disease 210pain suppression, see analgesics, NSAIDspaliperidone 244palonosetron 219pamidronic acid 211pancopride 219pancuronium 490panipenem 525panobinostat 156, 294pantoprazole 410Papaver somniferum 269papaverine 269, 287paracetamol (acetaminophen) 84, 92– metabolism 82paraldehyde 94parallel synthesis 10paraquat 397parasitic infections, see anthelmintics,

antiprotozoalsparasympathomimetics, see cholinergicsparecoxib 456parenteral dosing (injection) of drugs 15–17paricalcitol 489Parkinson’s disease, see antiparkinsoniansparomomycin 81

Index 595

paroxetine 10, 17, 251PARP inhibitors 300, 372pazinaclone 426pazopanib 369, 406pazufloxacin 519PDE, see phosphodiesterasepefloxacin 514, 518PEG (poly(ethylene glycol)) 92, 348peldesine 439Pelletier, Pierre Joseph 413pemetrexed 553pemirolast 515pemoline 128P-glycoprotein (P-gp) 13, 16P-glycoprotein inhibitors 254, 290, 367L-penbutolol 47, 320, 321penclomedine 402penciclovir 443penethamate 527penfluridol 241penicillamine 99, 159, 339penicillin 522penicillin F 522penicillin G 522, 527penicillin V 522, 527penicillinase inhibitors 182pentachlorophenol 84pentamidine 120, 127pentanols, solubility 36pentazocine 2742-pentenylpenicillin 522pentobarbital 41, 198, 202pentopril 338pentostatin 438pentoxifylline 441pentoxyverine 221peptic ulcers, see antiulcerativespeptidases 166peptide deformylase inhibitors 356peptides 166, 347, 358–360peptidomimetics 347–361peramivir 129perampanel 404perazine 306PERC 57pergolide 294perhexiline 230pericyazine 308perindopril 337peristaltic stimulants, see gastroprokineticsperoxides 97perphenazine 109, 308perzinfotel 211pethidine 251

PGE1 539PGE2 538PGG2 538P-gp 13, 16pharmacokinetics–structure relationship 5phases of clinical development 5phenacemide 195phenacetin 85, 91phenanthrene 47phenazone 4, 173, 181phenazopyridine 62, 405phencyclidine 37, 116, 264phendimetrazine 280phenelzine 137phenethicillin 527phenethylamines 267–290pheneturide 193, 195phenformin 124, 131pheniramine 230phenmetrazine 280phenobarbital 17, 46, 197phenol 36, 82, 84phenols 82– prodrugs 84, 164, 186phenothiazine 303phenothiazines 301–309phenoxybenzamine 52phenoxymethylpenicillin 522, 527phenprobamate 190phenprocoumon 142phensuximide 178phentermine 271phentolamine 120, 125, 320phenylacetic acid 149N-phenylacetylglutamine 149phenylbutazone 4, 46, 1804-phenylbutyric acid 149phenylephrine 282phenylethylamines 267phenyl groups, unsubstituted 46phenylketonuria 408phenylpiracetam 175phenylpropanolamine 280phenytoin 17, 179, 213pheochromocytomas 51phocomelia 189pholcodine 108, 332pholedrine 273phosphates 213phosphodiesterase III inhibitors 247, 406phosphodiesterase IV inhibitors 170, 195,

287, 400, 444, 508phosphodiesterase V inhibitors 299, 442,

443

596 Index

phosphonates 209phosphonic acids 209phosphoric acid derivatives 213photosensitizers 90, 142, 564, 565phototoxicity 18, 90phthalimide, pKa 172physostigmine 190phytoestrogens 88picoprazole 396picosulfate 207picotamide 366Pictet–Spengler reaction 269picumast 247pidotimod 174pilocarpine 378, 380pilsicainide 344pimavanserin 257pimecrolimus 559pimobendan 411pimonidazole 383pimozide 240pinacidil 400pinaverium 117pinazepam 169, 470pindolol 323pioglitazone 178pipamperone 242pipecurium 118, 491pipecuronium 491pipemidic acid 514, 518piperacillin 527piperazine 109, 250piperazines 109, 227–266piperidine, pKa 110piperidines 227–266piperoxan 320pipotiazine 308piracetam 173, 174pirazolac 504pirbuterol 285pirenzepine 313piretanide 455, 508pirfenidone 406piribedil 250piritramide 239piritrexim 408pirlindole 293pirmagrel 149pirmenol 71, 233piroxicam 186, 396, 460piroximone 182, 400pirozantrone 496pirprofen 499pitavastatin 550

pivampicillin 526pixantrone 496pizotifen 255, 315pizotyline 255, 315plasma clearance 7plasma half-life 6, 15plasma protein binding 6Plasmodium falciparum 413platelet aggregation inhibitors 265, 366, 439,

539, 540platelet glycoprotein IIb/IIIa blockers 265,

361, 362platinum-containing drugs 158PLD-118 160pleconaril 385plerixafor 565plinabulin 381polar surface area 14, 16polidocanol 77poly(ADP-ribose) polymerase inhibitors 386polycyclic hydrocarbons 47poly(ethylene glycol) 92, 348polyols 71–81polythiazide 453pomalidomide 196ponalrestat 502pores, hydrophilic 14, 119posaconazole 391potassium channel blockers 150, 263, 398,

435, 462, 463potassium channel openers 174, 200, 400,

407potency of drugs 8, 18Poulenc Freres 215pozanicline 259PPAR-γ agonists 151, 152, 178, 179practolol 47, 321, 324pradefovir 443pralatrexate 552pralidoxime 118, 398pramiconazole 392pramipexole 115, 274pramiracetam 174pramiverine 257pranlukast 509pranoprofen 501prasugrel 265pravastatin 549prazepam 93, 169, 469praziquantel 288prazosin 415, 425preclamol 274preclinical development 5prednisolone 479

Index 597

prednisone 17, 479pregabalin 161pregnanolone 483preladenant 245premazepam 475prenalterol 324prenylamine 229, 273pridinol 71, 232prilocaine 343prils 335–340primaquine 414, 421primidone 197prinomastat 371probenecid 17, 458, 507probucol 87procainamide 134, 215, 216procaine 215procarbazine 117, 137procaterol 283prochlorperazine 109, 307procyclidine 71, 233prodrugs– amides as 114, 167– of alcohols 164, 186, 213, 214– of amides 214– of amines 112–114, 167, 187– of carboxylic acids 167, 186– of ketones 140– of phenols 84, 164, 186– of thiols 213progabide 149progesterone 477, 482progesterone receptor modulators 489progestins 477progestogens 482–488proglumide 150proguanil 131prokinetic drugs, see gastroprokineticsprolactin 274prolactin inhibitors 294–296promazine 101, 301, 304, 393promethazine 4, 301, 303prontosil 62, 450propafenone 325propantheline 221propargylamine, pKa 110propentophylline 441propericiazine 308propiomazine 303propiram 227, 401propiverine 220propofol 82, 84propoxyphene 228propranolol 47, 320, 321, 322

propylamine, pKa 110propylbenzene 912-propyl-2-pentenoic acid 148propylthiouracil 201, 434propyphenazone 181proquazone 419prostacyclins 538prostaglandin analogs 538–542prostaglandin antagonists 156, 505prostaglandin E1 (PGE1) 539prostaglandins 538prostatic hyperplasia 278, 279, 416proteases 166proteasome inhibitors 352protein binding 6protein kinase C inhibitors 375prothipendyl 304, 393protionamide 400protizinic acid 303proton pump inhibitors 104, 370, 396, 409,

410protozoals, see antiprotozoalsprotriptyline 312proxyphylline 441PRT 054021 367prucalopride 134, 220prulifloxacin 114, 520pruritus (itching), see antipruriticspseudohypericin 90psoralens, see 8-methoxypsoralenpsoriasis 489, 509, 551PT-523 552pteridines 415, 416pulmonary hypertension 124, 369, 370, 458purine derivatives 435–439, 443–445pyrantel 124pyrazinamide 399pyrazofurin 429pyrazolone antipyretics 172pyrexia, see antiinflammatoriespyridine 395, 397pyridine N-oxides 70pyridines 393–410pyridinol carbamate 399pyridostigmine 399pyrilamine 225, 227pyrimethamine 405pyrimidine N-oxides 70pyrimidines 25, 27, 3931-(2-pyrimidinyl)piperazine 250pyritinol 403pyronaridine 417

598 Index

qquaternary ammonium salts 118quazepam 201, 470quercetin 88quetiapine 19, 319quinacrine 420quinagolide 208, 274quinapril 338quinazoline 416quinazoline N-oxides 466quinazolines 415quinazolones 418, 419quinethazone 452quinidine 17, 42, 421quinine 4, 172, 413, 421quinoline 416quinolines 24, 412–425quinolonecarboxylic acids 4, 514–521quinupramine 111, 314quinupristin 563

rR406 366R-115777 380R-115866 391R-126638 392R-406 366rabeprazole 409raclopride 218radioactive tracing agents 53radiosensitizers 383, 564, 565ragaglitazar 152raloxifene 260raltegravir 369raltitrexed 553ramatroban 156, 293rambazole 391ramelteon 275ramipril 337ramosetron 381ranitidine 102, 132ranolazine 327, 345rapacuronium 490rapamycin 557, 558rasagiline 113, 271rate of elimination 7ravuconazole 389razaxaban 370reactive compounds, toxicity 17rebamipide 163reboxetine 228, 322recainam 3455α-reductase inhibitors 487reflux esophagitis, see antiulceratives

regadenoson 437remifentanil 164, 243remikiren 349, 357remoxipride 218renin 335renin inhibitors 336, 357renzapride 219repaglinide 510repartitioning agents 286repinotan 249repirinast 510Research Triangle Institute 415reserpine 165, 299resistance, antibiotic 523respiratory stimulants 234, 253, 263, 399retigabine 136, 394, 404retinoic acid agonists 152, 153, 509retinoic acid metabolism blocking agents

391revaprazan 370, 406reverse transcriptase inhibitors 294, 317rhein 89rheumatoid arthritis 98, 158, 159, 169, 352,

366rhizoxin 564Rhone-Poulenc 301ribavirin 429ribostamycin 80ridogrel 149rifabutin 562rifampin 17, 563rifapentine 17rifaximin 563rilmazafone 167rilmenidine 125rilpivirine 405riluzole 385rimantadine 37, 115rimiterol 284rimonabant 234riociguat 370, 407risedronic acid 212risperidone 244ritalinic acid 251ritanserin 256ritipenem 525ritodrine 282ritonavir 17, 351rivaroxaban 176rivastigmine 188, 190, 273rivoglitazone 179rizatriptan 292RNA polymerase inhibitors 562Ro 03-8799 383

Index 599

Ro 31-1118 325Ro 31-7453 375Ro 48-6791 471Ro 48-8684 471rocuronium 491rodenticides 48, 299rofecoxib 456roflumilast 170, 396, 400rolapitant 111, 265rolipram 175, 275rolitetracycline 494romidepsin 360ropinirole 275ropivacaine 344roquinimex 461roscovitine 444rosiglitazone 178rosoxacin 515Ross, Warren 415rosuvastatin 550rotigotine 274roxatidine 264roxifiban 120, 188, 362roxithromycin 560RPR 109881A 555RSR-13 154rubitecan 423ruboxistaurin 375rufinamide 390rufloxacin 102, 518rule of five 13Runge, Friedlieb 82rupatadine 114, 255, 316

sS-8307 543, 544S-8308 544sabeluzole 246, 327safinamide 117, 207safrole 42sagopilone 564salbutamol 72, 284salicin 497salicylamide 168, 512salicylamide O-acetic acid 512salicylates 497, 498, 511–513salicylic acid 497, 498, 511salmeterol 285salsolinol 287salt formation, advantages 107sapacitabine 432sapropterin 408saquinavir 351saracatinib 374

saralasin 335, 543sarizotan 401sartans 543–547satavaptan 262satraplatin 158saxagliptin 345Saxl, Paul 451Schering 215schizophrenia 418Schmiedeberg, Oswald 188scopolamine 96, 222secnidazole 60, 73, 383secobarbital 41, 198γ-secretase inhibitors 353, 355sedatives, see hypnoticsseizures, see antiepilepticsP-selectin inhibitors 24selegiline 271seletracetam 43, 175selodenoson 438selumetinib 372semagacestat 355sematilide 217senicapoc 151seratrodast 150sergliflozin etabonate 186serine protease inhibitors 127serotonin 292serotonin antagonists 244, 245, 255, 296serotonin 5-HT1 agonists 219, 248serotonin 5-HT1,2C agonists 250serotonin 5-HT1A agonists 23, 219, 245, 248,

249serotonin 5-HT1A antagonists 245, 257serotonin 5-HT1A,B,D,F agonists 258serotonin 5-HT1B,1D agonists 291–293serotonin 5-HT2 antagonists 240, 256, 277serotonin 5-HT2A agonists 275serotonin 5-HT2A antagonists 236, 250serotonin 5-HT2A,2C agonists 295serotonin 5-HT2A,2C antagonists 234serotonin 5-HT2C agonists 272serotonin 5-HT3 antagonists 219, 223, 381serotonin 5-HT4 agonists 130, 218–220serotonin receptors 225serotonin reuptake inhibitors 228, 234, 236,

237, 248, 259, 270, 276serotonin transporter inhibitors 228sertaconazole 388sertindole 246sertraline 17, 230Sheehan, John C. 522sibrafiban 121, 362sibutramine 112, 272

600 Index

sickle cell disease 151, 509side-effects 16–20silanes 264, 509sildenafil 442silodosin 279silperisone 264simendan 411simvastatin 549sirolimus 558sitafloxacin 520sitagliptin 23, 273, 346sitaxentan 458skin rashes 18sleep disorders, see hypnoticssmall molecule drugs, future 9SmithKline Beecham 415SMO antagonists 366smoke 17SN-38 424SNS-032 258sodium channel blockers 130, 216, 217, 220,

224, 405, 408sodium/proton exchange inhibitors (NHE-1)

130, 131solabegron 281solifenacin 230solubility– alkanols 36– drugs 5, 10, 13, 14– ethers 91somatostatin analogs 360sorafenib 371, 396sorbinil 178sorbitol 71, 77sorivudine 434sotalol 83, 268, 286sparfloxacin 144, 520spectinomycin 79spermicides 77spiramycin 562spirapril 337spironolactone 487splenda (sucralose) 51, 79squalene 548SR 121463 262SR-4554 384stains, see dyesstatins 548–550stavudine 433Sternbach, Leo 466steroids 477–491stibogluconate 158stimulants, see CNS stimulantsstiripentol 74

St. John’s wort 16, 90stomach 14Streptomyces 492streptomycin 122, 129streptozotocin 69strychnine 299succinimides 177, 178sucralose 51, 79sudoxicam 460sufentanyl 243sulbactam 524sulbenicillin 204, 528sulfadiazine 458sulfadoxine 134, 459sulfamethoxazole 17, 459sulfamic acids 207sulfamidochrysoidine 62sulfamoxole 459sulfanilamide 62sulfapyridine 459, 512sulfasalazine 62, 512sulfates 207sulfinpyrazone 180sulfisoxazole 459sulfluramid 457sulfonal 193sulfonamides 21, 450, 452–460; see also

sulfonylureassulfonates 206sulfones 26, 101, 106sulfonic acids 203–205sulfonic esters 206sulfonylureas 462–465sulfoxides 101, 104, 396, 397sulfoxone 87sulfur mustard 54sulindac 105, 503sulotroban 156sulpiride 217sulprostone 147, 541sulthiame 457sultopride 218sultosilic acid 205, 206, 513sumatriptan 291, 292sunitinib 113, 217suprofen 500surface, see topicalsurgery, antiseptic 82suriclone 426sweeteners, artificial 77, 79, 115, 205, 434sympathomimetics, see adrenergic agonistssynephrine 267, 282syphilis 451

Index 601

tT4, thyroxine 159tabimorelin 356TAC-101 509tachyarrhythmias, see antiarrhythmicstacrine 414, 420tacrolimus 557, 559tadalafil 299tafenoquine 421TAK-375 275TAK-442 170Takeda 543talabostat 355talampanel 476talampicillin 526talbutal 198talinolol 325talnetant 418talsaclidine 44, 264taltobulin 356tamibarotene 509tamoxifen 263tamsulosin 279tandospirone 249tanomastat 505tapentadol 274taranabant 171, 396tariquidar 367TAS-106 431tasosartan 546, 547tauromustine 69taxanes 554–556taxol 10, 554, 555tazarotene 509tazifylline 442tazobactam 524TBC-3711 369TBR-652 382tebufelone 85tecadenoson 438tecans 415, 423, 424tecarfarin 143tedisamil 263tegafur 434tegaserod 122, 130telaprevir 351telbivudine 433telcagepant 192, 354telithromycin 561telmisartan 546temafloxacin 517temazepam 138, 472temelastine 402temocapril 102, 338

temocillin 529temoporfin 564temozolomide 65, 382temsirolimus 558tenatoprazole 409tenidap 139, 459teniposide 90tenofovir disoproxil 210, 444tenoxicam 459tepa 55tepoxalin 504teprenone 141teprotide 335teratogenics 189terazosin 426terbinafine 48, 116, 271terbogrel 149terbutaline 3, 284terfenadine 226, 256terguride 294teriflunomide 169terodiline 229tert-alkylamine dealkylation 111tertatolol 320, 323tertiary alcohols 71, 73terutroban 162tesaglitazar 152, 206tesofensine 111, 112, 251testosterone 477, 486tetomilast 508tetrabenazine 287tetrachlorodioxin 52tetrachloroethylene 57tetracycline 493tetracyclines 492–495tetrahydrocannabinol (THC) 86, 146tetrahydrofolic acid 552tetrahydrofuran 91, 100tetrahydroisoquinolines 269, 287–290tetrahydropyran 100tetrahydrothiophene 100tetrazepam 468tetrazoles 146tezosentan 509thalidomide 172, 189, 195thalline 4, 173tham 115THC 86, 146thebaine 269theobromine 440, 451theophylline 440therapeutic index 5THF 91, 100thiabendazole 378, 386

602 Index

thiamazole 182, 379thiamphenicol 78thiazinamium 303thiazolidinediones 178, 179thiethylperazine 307thioacetamide 201thioamides 194thiocarbonyl compounds 201thioethers 100thioguanine 201, 439thiols 98– prodrugs 213, 214thionylan 227thiopental 199, 202thiophene S-oxides 102, 103thioridazine 17, 306thiotepa 55thiothixene 307thioureas 194thrombin inhibitors 349, 354, 363, 364; see

also antithromboticsthrombolytic drugs, see antithromboticsthromboxane antagonists 149, 150, 156, 542thromboxane synthase inhibitors 149, 380,

510thromboxanes 538thymidylate synthase inhibitors 418thyroxine, T4 159tiagabine 161, 240tiamenidine 127tianeptine 146, 313tiapride 217tiaprofenic acid 503tiaramide 224tiazofurin 429tibolone 484ticagrelor 439ticarcillin 529ticlopidine 17, 265ticrynafen 102, 103, 155tienilic acid 155tigecycline 495tilidine 43, 330tiludronic acid 212timolol 326timoprazole 396tinidazole 106, 382tinofedrine 232tiopronin 99, 162, 339tiotropium 96, 222tipifarnib 380tipranavir 143tiracizine 187, 313tirapazamine 70, 419

tirilazad 490tirofiban 361tiropramide 261tizanidine 123, 126tizoxanide 183TMC-207 417tobacco alkaloids 402tobramycin 80tocainide 343tocolytics (inhibitors of uterine motility)

282, 283, 286D-α-tocopherol 86tofisopam 476tolamolol 327tolazamide 463tolazoline 124, 320tolbutamide 52, 462tolcapone 85tolfenamic acid 506tolmetin 503toloxatone 176tolperisone 242tolrestat 163tolterodine 232toluene 47o-toluidine 133, 341, 343tolvaptan 376tomopenem 525tomudex 553topical anesthetics, see local anestheticstopical antifungals, see antifungalstopical disinfectants 82, 87, 118topiramate 95, 207topixantrone 496topoisomerase I inhibitors 299, 415, 423,

424topoisomerase II inhibitors 416, 496topotecan 415, 424torasemide 463torcetrapib 191toremifene 263torsades de pointes 17torsemide 463tosedostat 156, 353tosufloxacin 516toxicity of drugs 17TPA-023 391trabectedin 288tramadol 330tramiprosate 204trandolapril 337tranexamic acid 160tranezamic acid 160tranilast 507

Index 603

tranquilizers, see antipsychotics, hypnoticstransplant rejection 557tranylcypromine 270trapidil 440travoprost 147, 540traxoprodil 283trazodone 247trefentanil 243tremor, see antidyskinetics, antiparkinsonianstreprostinil 540tretinoin (all-trans-retinoic acid, vitamin A

acid) 153triamcinolone 478triamcinolone acetonide 4791,2,4-triaminobenzene 62triamterene 408triazenes 64triazolam 470triazoles 387–392trichlormethiazide 453trichloroacetaldehyde 138trichloroacetic acid 138, 1481,2,4-trichlorobenzene 56trichloroethanol 74, 138triclabendazole 385triclopyr 155, 402tricyclic antidepressants, see antidepressantstriethylamine, pKa 110trifluoperazine 307trifluoroacetamides 166trifluoromethyl groups 51trifluorothymidine 433triflupromazine 305trifluridine 433triflusal 511, 512trigonelline 398trihexyphenidyl 233triiodobenzoic acid 75trimazosin 73, 426trimebutine 220trimecaine 343trimeprazine 305trimetazidine 252trimethadione 177trimethobenzamide 260trimethoprim 404trimetrexate 136, 409trimipramine 314tripamide 453tripelennamine 225, 227triprolidine 145, 231trocade 352troglitazone 17, 179trombopoetin agonists 153

tropane alkaloids 222–224tropisetron 223trospectomycin 79trovafloxacin 167, 516troxacitabine 138, 430tryptamine 107tuberculostatics 201, 399, 400, 417; see also

antibacterialsD-tubocurarine 289tubular secretion 15tubulin ligands 291tubulin polymerization inhibitors 356, 381tucaresol 138, 509tulobuterol 281TXA2 538tybamate 189tyramine 107, 267tyrosine kinase inhibitors, see antineoplasticstyrosinemia 142

uU-101387 246UCB 173udenafil 443UK-240455 427ulcers, gastric– drugs for treatment, see antiulceratives– NSAID-associated 497, 498ulifloxacin 114, 520ulipristal acetate 136, 490undesirable effects of drugs (adverse drug

reactions) 17–20unoprostone isopropyl 541unsaturated groups (alkenes) 40–44UR-8880 455uracilacetic acid 53, 433urapidil 248, 435urea cycle disorders 149urea 193ureas 28, 29, 192–199ureides 146urethanes (carbamates) 187–191uricosurics (enhancers of uric acid excretion)

88, 155, 180, 435, 458urinary acidifiers 116, 159urinary incontinence 220, 232, 238urogenital atrophy 263

vV-11294A 444vadimezan 505valacyclovir 437valdecoxib 456

604 Index

valium 468valnoctamide 148valproic acid 144, 148N-valproylglycine 162valrocemide 162valsartan 547vamicamide 238vancomycin 361vandetanib 373vanilloid-1 antagonists 25vanoxerine 241vapiprost 542vardenafil 443varenicline 272, 422vascular disrupting agents 381vasoconstrictors 126, 296, 505vasodilators– cerebral 221, 236, 283, 287, 298, 422, 440– coronary 66, 93, 94, 229, 230, 241, 278, 440– peripheral 236, 242, 250, 282, 283, 285,

401, 437, 441, 539, 540vasopressin agonists 360vasopressin antagonists 262, 376vasopressors (antihypotensives)

273, 282, 285, 407vasoprotectants 88, 182vatalanib 372, 421Vater, Wulf 446vecuronium 490vegetables 17VEGF inhibitors 371, 373veliparib 386velnacrine 414, 420vemurafenib 370venlafaxine 276veralipride 218verapamil 17, 277, 446verlukast 423vernakalant 330veronal 193verteporfin 565vertigo 401; see also motion sicknessvesnarinone 425vicriviroc 253vidarabine 436vigabatrin 43, 161vilazodone 248vildagliptin 342, 346viloxazine 280, 322vinblastine 297vinca alkaloids 291, 297, 298vincamine 298vincristine 297

vindesine 298vinflunine 298vinorelbine 297vinpocetine 298vinyl bromides 53vinyl chloride 49vinyl chlorides 52vinyl fluorides 43vinyl groups 40–43vinylbital 199viral infections, see antiviralsviramidine 429vismodegib 366vitamin A 153vitamin B3 398, 399vitamin B9 551vitamin C 77vitamin D analogs 488, 489vitamin D2 488vitamin D3 489vitamin E (tocopherol) 86vitamin H (biotin) 162vitamin K antagonists 143Vogl, Alfred 451volume of distribution 6volume, body fluids 7vomiting, see antiemetics, emeticsvon Mering, Josef 188, 193voreloxin 516voriconazole 389vorinostat 156VX-702 366

wWani, Mansukh C. 554warfarin 60, 139, 142, 349weight reduction, see anorexicsWestern yew tree 554willow bark extracts 497Willstatter, Richard 215Wintersteiner, Oskar 522Wong, Pancras C. 543worms, see anthelmintics

xxamoterol 327xanomeline 264xanthine oxidase inhibitors 439, 445,

510xemilofiban 363xibenolol 321ximelagatran 121, 362ximoprofen 499

Index 605

xipamide 454X-ray contrast agents 72, 75, 76

yYH1885 370, 406YM-150 367yohimbine 299

zzafirlukast 511zalcitabine 430zaleplon 371zaltoprofen 501zamifenacin 278zanamivir 122, 129zatebradine 277zatosetron 223ZD 9331 147, 552zebularine 429

zenarestat 502zidovudine 58, 432zileuton 192, 194zimeldine 71, 231ziprasidone 244zofenopril 164, 339zoledronic acid 212zolmitriptan 292zolpidem 52, 410zomepirac 503zonampanel 501zoniporide 131zonisamide 457zopiclone 427zopolrestat 502zosuquidar 254, 327zotarolimus 558zotepine 140, 318zuclopenthixol 308