SUBJECT INDEX

Bold numbers denote syntheses. a-adrenergic receptor, subclass, 477 acadesine, 281 central, 289 ACE inhibitors, 246 1,2,4-triaminobenzene, 61 effect on blood pressure, 19 1A/II a-sadrenergic, 52 acetazolamide, 311, 585 5-hydroxytripatamnine in drug design, 390 acidic proton, NSAIDs, 487 6-APA, 546 , 268 activation, 547 acne, 35 from penicillin, 546 acolbifene, 207 7-ACA, from cephalosporin C, 558 acridine, antimarials, 441 from penicillins, 562 acrivastine, 326 starting material, 561 actisomide, 616 7-ADCA, starting material, 563 activity vs potency, 63 7-amino deacetylcephalosporanic acid, acyclovir, 605 (see 7-ADCA) adenosine A1 receptors, 281 7-aminocephalosporanic acid (see 7-ACA) adinazolam, 506 a1-adrenergic agonist,COPYRIGHTED 84 adrenal MATERIAL cortex, 153, 169 abacavir, 607 adrenalectomy, 169 ablukast, 437 adrenalin, 43 ablukast, 446 agonist, b2-adrenergic, 48, 325 abortion, induction, 12 a-adrenergic, 281, 287 RU-486, 137 a1-adrenergic, 84 absorption, cholesterol, 451 adenosine, 603

Strategies for Organic Drug Synthesis and Design, Second Edition. By Daniel Lednicer Copyright # 2009 John Wiley & Sons, Inc. 633 634 SUBJECT INDEX

agonist, b2-adrenergic (Continued) amphetamine, 264 cholinergic, 336 ampicillin, 547 dopamine, 495, 496 amprenavir, 27 non-steroid progestin, 209 amprolium, 348 PPAR, 531, 535 ampyzine, 366 agonist-anatgonist opiate, 217, 222, 225 amquinate, 445 albuterol, 48, 324 amrinone, 338, 343, 616 albutoin, 293 amustaline, 524 alcoholism, treatment, 217 anabolic activity, 141 aldose reductase, 437 anastrozole, 309, 424 aldosterone, 153 androgens, abuse by athletes, 141 alertness, 283 anabolic, 141 alfuzocin, 478 controlled substances, 141 aliretioin, 37 angina, 54 alizapride, 424 angiotensin converting alkylating agents, 126 enzyme (see ACE) allergy, beta lactams, 546 angiotensin, 246 allopurinol, 304, 601 anileridine, 227 almotriptan, 391 anilorac, 578 alnitidan, 439 anitrazafen, 378 alovudine, 354 antagonist, a-2 adrenergic, 477 alprazolam, 506 a2-adrenergic, 280 altanserin, 487 a-adrenergic, 287, 468 altinicline, 327 b-adrenergic, 299, 438 alvimopam, 234 aldosterone, 153 alvocidib, 435 androgen, 150 Alzheimer’s disease, 91, 283, 327, 522 androgen, non-steroid, 208 Alzheimer’s, acetyl choline, 403, 522 angiotensin receptor, 285, 417 Alzheimer’s, acetylcholine, 91, 420 benzodiazepine, 507 Alzheimer’s, acetylcholinesterase, 522 canabinol, 297 Alzheimer’s, monoamine oxidase, 91 cholecystokinin, 508 ambrisentan, 358 dopamine b-hydroxylase, 295 amdinicillin, 549 dopamine, 332, 423, 533 amdoxovir, 608 endothelin, 253, 358 amedalin, 402 fibrinogen receptor, 30, 417 ametantrone, 113 GABA, 337 amfenac, 73 glucocorticoid, 137 amflutizole, 304 histamine H1, 276, 326, 360 amifloxacin, 456 histamine H2, 241, 276, 300, 307 amiloride, 365 , 81, 258, 326, 419, 436, aminoglutethimide, 339 446, 483 aminopenicillic acid (see 6-APA) neurokinin, 449 aminopyrine, 296 opiate, 215 aminorex, 264 progesterone, 137 amitriptyline, 106 serotonin H2, 370 amlexanox, 541 serotonin, 487 amodaquine, 442 thromboxanes, 319 amoxapine, 538 vasopressin, 498, 511 amoxicillin, 547 antiarrhythmic, 45 SUBJECT INDEX 635 antibacterial drugs, mechanisms, 454 atreleuton, 258 orally active, 52 atrial natriuretic peptide anticholinergic, 255, 366, 452, 454, (ANP), 92 515, 526 attention deficit syndrome, 283 anticonvulsant, 291 avanafil, 358 antidepressant spirones, 372–374, 469 avitriptan, 394 open chain, 57 azalanstat, 282 development, 57 , 475 non-tricyclic, 57 azepindole, 624 antifungal, non-conazole, 94–96 azetidone, beta lactam, 547 antihistamine, non-sedating, 326, 368, 409 azomycin, 271 phenothiazines, 532 azosemide, 63 antihypertensive, 54 AZT, 350 b-blockers, 50 aztreonam, 572, 573 antimalarials, history, 441 antimetabolite, 600 b1-adrenergic, 47 antipyrine, 296 b3-adrenergic, 51 antitussive, 221, 304 bacterial cell wall, 546 antrones, antineoplastic, 113 bamiphylline, 595 apaxifylline, 596 barbital, 363 aplaviroc, 375 barbiturates, 364 apoptosis, 434 barbituric acid, 338 appetite suppressant, 297, 439 batelapine, 510 apraclonidine, 290 bazedoxifene, 204 aptazepine, 511 b-blockers, 45 aptinagel, 97 antihypertensive, 50 , 581 injectable, 55 cascade, 1 mechanism of action, 54 argatroban, 30 selectivity, 54 aripiprazole, 370 Becket-Casy rule, 79 arprinocid, 611 bemarinone, 484 arrhythmia, 54 bemitradine, 608 arteflene, 470 bendacalol, 468 arzoxifene, 204 bendazac, 407 asenapine, 519 benziodarone, 383 asimadoline, 236 benzydamine, 407 asoprinosil, 138 beta lactam, broad spectrum, 557 aspirin, 14 beta lactamase, 547, 558 astemizole, 409 resitance, 549 asthma, 54, 48, 419, 432, 593 beta lactams, mechanism, 546 Atabrine, 521 betaine, 561 atazanavir, 28 bexarotene, 100 atenolol, 55 bexlosteride, 208 atilide, 46 biapenem, 555 atipamezole, 280 bidisomide, 81 atiprimod, 251 bifeprunox, 420 atiprosin, 625 bifonazole, 276 atorvastatin, 246 bindarit, 408 atrasentan, 254 binospirone, 469 636 SUBJECT INDEX bioactivation, reductive, 488 carbazeran, 474 testosterone, 141 carbuterol, 50 biogenesis, steroids, 119 cardiac contratction, 337 bioisosterism, 106, 147 cardiotoxicity, 57 bipolar disorders, 420 cardiovascular disease, 54 Birch, A. J., 128 carfentanil, 231 bisantrene, 115 carnidazole, 270 bismethylenedioxy (BMD), 176 cartazolate, 589 bladders, overactive, 51 carumonam, 573 blockers, calcium channels, 329–332, carvone, 470 422, 512 cataracts, 437 blood discrasias, 52 cefaclor, 566 pressure, 47, 54 cefadroxyl, 563 blood-brain barrier, 104, 289, 325, 409 cefamandole, 560 bolasterone, 144 cefdinir, 565 Bothrops jararaca, 246 cefetamet, 564 breast cancer, tamoxifen, 195 cefoxitin, 550, 569 bretazenil, 508 cefpirone, 561 brifentanil, 231 cefprozil, 564 bromfenac, 73 cefquinome, 561 bromonium ion, 149 cefradoxine, 567 bromperamole, 313 cefradoxine, 567 bronchospasm, 47 ceftobipirole, 565 bropirimine, 362 celecoxib, 259 brotizolam, 622 cell entry, HIV, 310, 375 bunaprolast, 97 proliferation, 452 buquinolate, 444 lifespan, 434 burimamide, 277 centochroman, (see ormoloxifene) buspirone, 372 central a-adrenergic agonist, 289 butenafine, 96 cephalexin, 562 butorphanol, 222 cephaloglycin, 562 cephalosporin C, 558 calcipotriene, 188 replacement of sulfur, 569 calcium channel blockers, 85, cephalothin, 559 329–332, 422 cephradine, 564 calcium, hypertension, 329 ceronapril, 247 muscle contraction, 329 cetirizine, 368 calusterone, 144 cetizoxime, 568 cambendazole, 416 CETP, 451 canabinol, 297 chloramphenicol, 52 cancer cells, 350 chlordiazepoxide, 501, 620 chemotherapy, 126 chloripramine, 526 candesartan, 417 chlormadinine, 164 candoxatril, 92 chloromycetin, 52 canrenone, 157 chlorphenamide, 63 capravirine, 284 chlorproethazine, 533 caprofen, 396 chlorpromazine, 106, 533 , 246 chlorprothixine, 528 carbamazepine, 526 chlorthalidone, 407 SUBJECT INDEX 637 chlorthiazide, 489 coccidiosis, poultry, 348, 444 chlortrianisene, 195 codeine, 213 cholesterol blood levels, 186 cold, common, 28 biosynthesis, 244 colestelone, 186 dietary, 451 collagenase, 293 feedback inhibition, 186 colon cancer, 579 steroid hormones from, 119 constipation, 16 synthesis, 186 contractile force, heart, 474 cholesteryl ester transfer protein (see CETP) contraception, race horses, 7 cholinergic, 327, 328, 336 contraceptive, non-steroid, 205 Chromobacterium violaceum, monobactam controlled substance, 225, 499 from, 572 controlled substances, androgens, 141 chromolyn, sodium, 432 controversy, RU-486, 137 chromonar, 431 coral, as source for prostaglandins, 12 cicletanine, 580 Corey lactone, 4 ciclindole, 394 coronary spasm, 329 cidofovir, 356 corticoids, discovery, 170 cicloprofen, 77 labile side chains, 182 cimetidine, 241, 276, 278, 359 corticosteroids, 169 cimicoxib, 260 cortisol, 169 cinalukast, 81 cortisone, 169 cinepazet, 367 cough remedies, 215, 221 cinoxacin, 472 COX-1, 71 cintazone, 472 COX-2, 71, 258, 389 cipemastat, 293 forerunner, 390 cipralisant, 283 COX-3, 71 ciprofloxacin, 458 criminal behavior, 505 ciprostene, 9 cromolyn, 436, 516 citalopram, 388 cyclazocine, 225 civemeline, 336 cycloguanil, 377 cladarabine, 602 cyclooxynase (see also COX), 3, 71, clamoxyquin, 445 279, 324 clazolamine, 293 cycloserine, 268 clemizole, 409 cylcophosphamide, 422 clobazam, 504 cyproheptadine, 107 clodanolene, 241 cytarabine, 376 clomacran, 522 cytomegalo virus, CMV, 605 clomiphene, 196 cytotoxic activity, 350 clonidine, 289, 469 cloperidone, 486 dabigartan, 418 clopidogrel, 584 dabuzalgron, 52 clopirac, 242 daledalin, 402 clorexolone, 405 D-allanine, cell wall cross links, 546 cloroquine, 441 daltroban, 70 clorsulon, 70 dapiprazole, 589 clothiapine, 539 darfenacin, 255 cloxacillin, 547 darglitazone, 67, 302 clozapine, 537 dazepinil, 510 coccidia, 348 DDC, 352 638 SUBJECT INDEX decitarabine, 377 diurnal cycle, 93 dehyroepiandrosterone (see DHEA) DNA gyrase, 454 delicacies, fatty, 38 insertion, 362 delmadinone, 165 supercoiled, 454 desipramine, 525 dofetilide, 47 deteronol, 45 Domagk, 61 devapezide, 508 donepezil, 92 dexamethasone, 179 donetidine, 360 dextromethorphan, 221 dopamine, 495 dezaguanine, 587 blockers, side-effects 333 dezocine, 226 b-hydroxylase, 295 DHEA, dietary supplement, 143 D2 receptors, 404 from sitosterol, 122 doramapimod, 99 diabetes, 65, 251, 437, 535 dothiepin, 530 non-insulin dependent (NIDD), 65 doxapram, 255 type II, 51 doxepin, 518, 530 diazepam, 501 DPP, 251 diazoxide, 489 dribendazole, 415 dibenzepin, 537, 540 droloxifene, 199 dichlorisone, 175 dronaderone, 385 dichlorphenamide, 63 droperidol, 334 diclofenac, 72 duloxetine, 59 dicoumarol, 429 dutasteride, 151 didrogesterone, 169 dyes, antineoplastic 113 dienestrol, 193 diethazine, 532 ecalcidine, 189 diethylstilbestrol, 193 econazole, 274 differentiation, epithelial, 35 edatrexate, 612 difloxacin, 457 edoxudine, 349 digitoxin, 337 efavirenz, 471 dihydralazine, 473 elantrine, 527 dihydrofolate reductase (see DHFR) emedastine, 409 dihydrotestosterone, 141 emtricitabine, 356 diltiazem, 329, 513 enadoline, 236 dimefline, 433 enalapril, 247 dimetacrine, 522 enantioselective (see synthesis, dinoprost, 7, 12 enantioselective) diosgenin, 121, 165 endopeptidase, ANP, 92 dipeptidal peptidase (see DPP) endothelin, 253 diphenhydramine, 276 endothelium, vascular, 580 Discorea, steroids from, 121 englitazone, 69, 303 discovery, corticosteroids, 170 enilconazole, 274 estrogens, 191 enolicam, 499 disobutamide, 79 enpiroline, 325 disopyramide, 79, 615 enrofloxacin, 458 disoxaril, 267 enviradine, 411 diuretics, “high ceiling”, 63, 90 enviroxime, 411 organomercurial, 63 enzyme, proteolytic, 32 potassium sparing, 365 eperzolid, 265 SUBJECT INDEX 639 epilepsy, 337 etorphine, 219 NMDA, 97 etretinate, 37 epinephrine, 43 evolution, Darwinian, 556 episteride, 153 eye inflammation, 288 eplerenone, 157 equivalence, 5-membered heterocycles, 300 fadrazole, 581 benzene and pyridine, 324 false substrate, 348, 601, 605 dibenzazepine and dibenzoxepin, 518 famotine, 464 phenol and sulfonamide, 45 fananserin, 371 sulfonamide and phenol, 45 fanetizole, 300 tetrazole and carboxyl, 285 farglitazar, 69 trigonal sp2 carbon and nitrogen, 518, farnesol, 119 530, 587 farnesolation, 452 equivalence sulfur and methylene, 569 farnesyl transferase, 452 erbuzole, 282 fat blocker, 38 ergosterol, biosynthesis, 273 fatty acid, mimics, 80, 97 eritadenine, 609 felodipine, 330 erlotinib, 480 fenacs, 71 ertapenem, 556 fenclosic acid, 298 ertiprotafib, 532, 535 fenisorex, 439 esmolol, 55 fenobam, 291 estazolam, 506 fenoldapam, 497 estradiol benzoate, 125 fenquizone, 484 estradiol cypionate, 125 fentanyl, 229 estradiol, 124 fentiazac, 298 estramustine, 126 fibrinogen, binding, 30, 417 estrofurate, 126 blood clotting, 30, 417 estrogen, total synthesis, 131 filaminast, 83 alkylating, 126 finasteride, 150 discovery, 191 Fischer indole synthesis, 389 hormone replacement, 125 flavodilol, 434 oral activity, 125 flavone, 433 receptor binding, 193 flavoperidol, (see alvocidib) estrone, 124 flavoxate, 434 etanidazole, 272 fletazepam, 504 ethacrinic acid, 90 floctafenine, 446 ethanolamine, 54 flordipine, 331 ethionamide, 323 flosequinan, 462 ethisterone, 128 fluanisone, 368 ethitoin, 292 flubiprofen, 76 ethonam, 272 flucindole, 395 ethosuximide, 257 fluconazole, 306 ethynerone, 132 fludarabine, 601 ethynodiol diacetate, 130 fludrocortisone, 173 etintidine, 278 fluid, accumulation, 498 etonitazine, 410 flumezanil, 508 etonorgestrel, 134 flumizole, 279 etoperidone, 372 flunidazole, 271 etoprine, 345 flunixin, 324 640 SUBJECT INDEX

fluomethasone, 181 grepafloxacin, 459 fluoroprednisolone, 174 Grewe synthesis, 219 fluotracen, 111 griseofulvin, 386 fluoxetine, 57, 622 guanoxone, 468 fluoxymestrone, 149 fluparoxan, 622 hair growth, 357 fluproquazone, 483 Halcionw, 505 fluprostenol, 7 hallucinations, 225 fluradoline, 517 haloperidol, 332, 368, 533 fluspiperone, 335 Hauser, rearrangement, 73 fluspiriline, 335 HDL, high density lipoproteins, 451 fluticasone, 184 heart failure, 337 fluvastatin, 401 rate, 47 fluverestant, 128 helminths, 414 fluvoxamine, 60 hemiasterlin, 34 folates, 611, 612 hepzidine, 108 synthesis, 344 heroin, 213 folic acid, 344, 481 herpes virus, 349 folinic acid, 344 histamine H3 receptors, 283 fosphenitoin, 293 HIV, binding site competitor, 310, 375 fostedil, 422 drug cocktail, 542 frentizole, 422 replication, 22, 284 furagrelate, 385 resistance, 354, 362 furaprofen, 385 RNA genome, 350 furosemide, 63 transcriptase, 350 HMG-CoA reductase, 244 GABA, 585 hormone replacement therapy, 125 gaboxadrol, 585 human immunodeficeiny galdansetron, 520 virus (see HIV) ganciclovir, 606 hycanthone, 528 garenoxacin, 461 hydolozine, 288 Gassman, synthesis, 73 hydracarbazine, 341 gastric acid, 413 hydralazine, 474 gemcitabine, 350 hydrochlorthiazide (HCTZ), 489 gepirone, 373 hydrocodone, 215 gestodene, 132 hydrocortisone, 172 gestonerone, 137 hydroxyglutarate, 244 gevotroline, 624 hydroxylation, metabolic, 296, 368, 450 glafeninie, 446 hydroxymethylglutaryl CoA, glaucoma, 290, 299, 313, 585 (see HMG-CoA) gliamilide, 66 hydroxyprogesterone, 163 glimepiride, 257 hydroxytamoxifen, 198 glitazone antidiabetics, 67, 301–303 hydroxyzine, 368 glutethimide, 339 hypertension, 54 glyburide, 66 ACE, 19 glyhexamide, 89 refractory, 357 good lipoproteins, 451 hypertrophy, prostate, 476 gout, 304, 412 hypolipidemic, 244, 251, 451, 531 Grave’s syndrome, 356 hypotensive, 357 SUBJECT INDEX 641 ibafloxacin, 456 cyclooxygenase, 4, 14, 71, 241 IBS, 16, 236, 449 DHFR, 344 ibufenac, 71 DNA gyrase, 454 ibuprofen, 75 DPP, 251, 252 ibutilide, 46 ergosterol biosynthesis, 203 iclaprim, 347 farnesyl transferase, 452 icopezil, 420 gastric acid, 413 icotidine, 360 histamine H1, 368 idazoxin, 469 HMG-CoA reductase, 244 ifetroban, 320 ileus, 233 igmesine, 236 lypoxigenase, 4, 97 ileus, surgery, 233 mediators, allergy, 432, 516, 541 imafen, 580 microtubule, 282 imiloxan, 281 neoangiogenisis, 402 imipenem, 552, 571 NMDA, 97 imipramine, 518, 522, 524 NNRTI, 284, 471, 542 imiquimod, 628 pancrealipase, 38 immortality, neoplasms, 434 PDE, 358, 593 imolamine, 305 phopholipase A2, 170, 397, 398 inactivating link, 55, 182, 233 platelet aggregation, 8, 18, 30, 319 incontinence, 255, 449, 451 protease, viral, 22 incretin, 251 protein kinase, 98, 311, 479 indacrinone, 90 renin, 20 indinavir, 25 reverse transciptase, 350, 352–356 indiplon, 591 sialidase, 320 indomethacin, 91, 396 sodium-potassium pump, 413 indoprofen, 405 SSRI, 57 indorenate, 399 TNF-a indoxole, 390 tubulin formation, 34 influenza, avian, 320 tyrosine kinase, 403, 448 epidemic, 320 viral integrase, 362 inhibitor, ACE, 246 xanthine oxidase, 304, 600 acetyl choline, 255 ink, ball point pen, 113 acetylcholinesterase, 522 insufflation, 432 aldose reductase, 437 insulin, 251 angitensingenase, 19 in diabetes, 65, 67 ANP, 92 resistance in NIDD, 67 aromatase, 308, 339, 424, 581 sensitivity, 535 beta lactamase, 567 integrase, viral, 362 betal lactamase, 551 interaction, non-bonding, 90 blood coagulation, 429 interferon, inducer, 362 cAMP, 593 intestinal motility, 227 cancer progression, 35 intranasal delivery, 222 CETP, 451 intraocular pressure, 290, 313 cholesterol synthesis, 186 intriptylline, 108 cholesterol synthesis, 244 iodoxifene, 198 collagenase, 293 irbesartan, 285 competitive, sulfa drugs, 61 irritable bowel syndrome (see IBS) COX-2, 258 irtemazole, 412 642 SUBJECT INDEX isatin, 625 lipoxynease, 4 isobuzole, 312 lisinopril, 247 isocarboxazide, 267 lisofylline, 597 isomazole, 588 lixivaptan, 511 isoniazide, 267, 364 lofemizole, 279 isoprene pathway, 119 lofentanil, 231 isoproteronol, 45 lometrexol, 614 isopyrine, 296 Lomotilw, 228 isostere, sulfur-methylene, 355 longevity, and antibacterial drugs, 61 isoxepac, 518, 530 loracarbef, 571 isoxycam, 488 lorazepam, 502 istradefylline, 597 losartan, 285 itasetron, 418 losoxantrone, 115 itazigrel, 279, 299 loteprednol, 184 izonsteride, 209 lovastatin, 400 loxapine, 538 Kaposi sarcoma, 63 lubiprostone, 16 ketazocine, 225 lucanthone, 528 ketobemidone, 228 ludes, 483 ketoconazole, 274 lupitidine, 278, 361 ketoprofen, 78 lynestrol, 130 ketorolac, 243 kinases, cell proliferation, 98 malaria, 440, 521 malformation, 340 labetolol, 50 maprotilene, 111 labor, induction, 12 maraviroc, 310 lacidipine, 332 maribavir, 411 ladostigil, 92 marijuana, 435 lamotigrine, 378 market, benzodiazepines, 499 lanoconazole, 275 mast cells, 432 lanosterol, 119 mazapertine, 369 large game, 219 mechanisms, antibacterial drugs, 454 lasoxifene, 201 medazepam, 503 lavoltidine, 307 medorinone, 616 LDL, low density lipoproteins, 451 mefloquin, 443 leg, restless, 423 megesterol, 164 lenalidomide, 340, 406 melagartan, 33 leprosy, 405 melatonin, 93 letrozole, 308, 424, 581 melengesterol, 167 leukotrienes, asthma, 182, 419 melitracen, 109 levallorphan, 221 meperidine, 226 levamisole, 579 mephenitoin, 292 levonorgestrel, 131 mercaptopurine, 600 levorphanol, 221 meropenem, 555 Libriumw, 501 mesclazone, 623 lifesapn, cells, 434 mestranol, in oral contraceptives, 129 linezolid, 265 metabolism, inversion, 78 linpiride, 403 ester cleavage, 55 lipoproteins, 451 hydroxylation, 238, 296, 450 SUBJECT INDEX 643

N,dealkylation, 80 mitoxantrone, 113, 549 olasalazine, 62 mivobulin, 615 reductive activation, 91 modafinil, 84 prontosil, 61 monobactam, fermentation, 572 sulfasalazine, 62 , 448 metaproteronol, 44 mood-altering properties, 499 methacrine, 441 morphinan, 221 methadone, 79 morphine, 213 methantheline, 515 morphine, antidote, 219 methaqualone, 483 isolation, 213 methenolone, 147 structure determination, 214 methicillin resistant Staph. Aureus., 547 simplification, 223 methicillin, 547 MRSA, 547 methixine, 529 mubritinip, 311 methopholine, 465 mucus, gastric, 14, 71 methosalen 431 multidrug resistance, 556 methotrexate, 611 muraglitazar, 69 methsuximide, 257 muscarinic, 328 methycyclothiazide, 490 muscimol, 585 methylprednislone, 178 mushroom, amanita, 585 methyltestosterone, 143 methyprylon, 341 nabilone, 436 methysergide, 390 nadolol, 101 metiamide, 278 nadrolone, 141 metiamide, 280 nafoxidine, 201 metolazone, 485 naftidine, 96 metopimazine, 535 nalidixic acid, 454, 618 metopon, 215 nalmexone, 217 metranol, 125 nalorphine, 215 metronisazole, 270 naloxone, 219 mevalonic acid, 244 naltrexone, 217 mevastatin, 244 napitane, 104 mexrenoate, 157 napsagartan, 32 mibolerone, 142 naratriptan, 394 miconazole, 274 narcolepsy, 84 microconazole, 274 nasal decongestant, 56, 287 Micronasew,66 natural products, marine, 34 microskeleton, cell, 34, 282 nausea, cancer chemotherapy, 418, 423 microtubules, 34, 282 naxifylline, 598 midazolam, 507 NCI, 113 mifepristone, 137 nebivolol, 438 migraine, 390, 438 nefazodone, 309 milk, irradiation, 429 nematodes, 414 milrenone, 616 neoangiogenisis, 402 milrinone, 338, 616 nepicastat, 295 minalrestat, 467 nequinate, 445 minaprine, 343 nerve transmission, 43 minoxidil, 357, 489, 508 nervous system, autonomic, 43 misoprostol, 12, 14 b-adrenergic, 45 644 SUBJECT INDEX netoglitazone, 303 ocinaplon, 590 neuraminidase, 320 octazemide, 579 neurokinins, 449 octriptyline, 109 neurotransmitter, 54 ofloxacin, 458 nevirapine, 542 olopatadine, 519 nicotine, smoking, 497 olsalazine, 62 nicotinic, 327 omaciclovir, 606 nifedipine, 330 omeprazole, 413 nifemazone, 296 ometidine, 278 niflumic acid, 324 omoconazole, 276 nifurazone, 240 onapristone, 139 nifurpirinol, 240 ondansetron, 418, 520 nifurquinazol, 479 ontazolast, 419 nimazone, 293 opioid receptor kappa, 225, 235 nimodipine, 330 sigma, 236 nisoxetine, 57 opium, 213 nitric oxide, 580 oral absorption, cephalosporins, 562 nitrofuran, 239 penicillins, 547 nitrogen mustards, 126, 369, 475, 524 oral contraceptives, 129 nitromifene, 196 orlisat, 39 nitroxyl radical, 488 ormoloxifene, 206 nivaldipine, 330 oseltamvir, 321 nizatidine, 300 ospemifene, 200 N-methyl D-aspartate (see NMDA) osteoarthritis, 71 nocodazole, 415 osteoporosis, estrogens, 191 non-insulin dependent diabetes Vitamin D, 186 (NIDD), 65 ovulation, induction, 196 nonnucleoside reverse trancriptase inhibitor inhibition, 128 (see NNRTI) oxabendazole, 414 non-sedating, antihistamine, 325 oxagrelate, 476 nonsteroid antiinflammatory agents oxamniquine, 451 (see NSAID) oxaprotiline, 112 norepinephrine, 43 oxaprozin, 262 norethandolone, 142 oxazepam, 502 norethindrone, 129 oxazolidinone, antibacterial, 265 norethinodrel, 129 oxiconazole, 274 norgestrel, 131 oxandrolone, 147 norgestrienone, 134 oxmetidine, 278, 359 norgesttrienone, 134 oxolamine, 304 normethandrolone, 141 oxolinic acid, 455 norsteroids, by sequential ring oxprenolol, 55 synthesis, 134 oxycodenone, 217 Torgov-Smith synthesis, 131 oxyphenbutazone, 297 nortryptiline, 102, 107 ozolinone, 301 NSAID, 3 ulcerogenesis, 14 pamaquine, 442 p-aminobenzoic acid, and sulfa drugs, 61 ocaperidone, 336 pancreatic beta cells, 65, 301 ocfentanil, 230 pantoprazole, 414 SUBJECT INDEX 645 papaver bracteum, 217 pimobendan, 343 papaver somniferum, 213 pimozide, 334 papaverine, 463 b-pinene, 597 parecoxib, 260 piperazine, in CNS drugs, 368 Parkinson’s disease, 104, 423 piperoxan, 468 PDE V, 598 piquindone, 626 selectivity, 83 piquizil, 477 pefloxacin, 456 pirbencillin, 549 peledesine, 591 pirbulterol, 325 pelitinib, 448 piritrexim, 614 pelretin, 38 pirmagrel, 582 pelrinone, 361 pirolate, 627 pemirolast, 617 piromidic acid, 618 penicillin, 546 piroxantrone, 114 absorption, oral, 548 piroxicam, 402, 488 antibacterial spectrum, 549 pirprofen, 77 fermentation, 546 pirquinozol, 625 Gram positive, 548 pivampicillin, 548 penicillin, 545 plasmodia, 441 selectivity, 546 platelet aggregation, 8, 30 source of 6-APA, 547 pobilukast, 81 source of 7-ACA, 562 ponalrestat, 475 source of 7-ACA, 562 poppy, dried sap, 213, 216 Penicilliun notatum, penicillins from, 546 potency vs activity, 63 pentamorphone, 219 potentiating groups, additive effects, 173 pentazocine, 225 potentiation, fluorine, 173 pentiapine, 512 poultry, coccidia, 348, 444 pentopril, 250 pramipexole, 423 pentoxyfylline, 596 prasugrel, 584 pepstatin, 19 prazocin, 477 peptidoglycans, cell wall, 546 prednisolone, 172 peptidomimetic drugs, inactivation, 32 prednylene, 178 perindopril, 249 pregnancy, 128 peroxisome proliferator activated receptors premafloxacin, 460 (see PPAR) Premarinw, 121 petit mal, 257 prenalterol, 57 pharmacophore, 239, 269, 332, 343, 383 presynaptic, 57 protease inhibitors, 27 prindoxan, 344 rings, 43 prizidilol, 342 phenazocine, 224 prodrug, 623, phenitoin, 292 prodrugs, 313, 343, 446, 488, 548, 623 phenoxilate, 227 profens, 75, 385, 397, 405 phentolamine, 288 profens, metabolic inversion, 78 phentolamine, 46 progesterone, 128 phenylbutazone, 296, 472 11-hydroxylation by fermentation, 170 phosphodiesterase (see PDE) by perfusion, 170 phosphorus, rarity in drugs, 422 inverted CD configuration, 168 picenadol, 229 potentiating groups, 162, 165 piclamilast, 83 role in female cycle, 161 646 SUBJECT INDEX proguanyl, 378 rabapprazole, 414 prontosil, 61 ragaglitazar, 535 propizepine, 540 ralitrexed, 482 propranolol, 54 raloxifene, 204 propylthiouracil, 356 raltegravir, 362 prorenone, 155 raluridine, 354 proroxan, 469 ramelteon, 93 prostacyclin (PGI), 8 ramipril, 249 prostaglandins, as contraceptives, 7 ranitidine, 241, 276, 361 biogenesis, 3 ranolazine, 367 effect on gi tract, 16 reasoning, elegant, 120 from soft coral, 12 reboxetine, 58 gastric protection, 14 receptor binding, 90 inflammation, 3 receptor binding, irreversible, 28 numbering, 2 receptor, a-2 adrenergic, 477 prostatic hypertrophy, 145 benzodiazepines, 500 protease, and angiotensin, 19 opiate, 225 aspartil, 22 recovery, post-surgical, 233, 429 and HIV, 22 Regain, trade name, 357 renin, 19 regulation, viscera, 449 FDA approved, 22 remifentanil, 233 protozoa, 269 renin-angiotensin system, 246 protriptyline, 109 replication, bacterial, 454 proxazole, 305 research, low level, 340 Prozacw, 57 resistance, antimalarials, 441 pseudomonas, resistance, 560 antinemotodals, 414 psoralen, 431 bacterial, 556 psoriasis, 431 multidrug, 556 kinases, 98 restless leg syndrome, 423 psychopharmacology, 106 retinal, and vision, 35 pteridines, function, 577 retinoic acid, 35 pulmonary hypertension, 253 retinoids, 99 pyrazinamide, 364 retrovirus, 348 pyrimethamine, 345 reverse transcriptase, 350, 471 pyrimethamine, 377 revolution, treatment of CNS disease, 533 Quaalude, 483 rheumatoid arthritis, 293 quaternary salts, 515 kinases, 98 quazinone, 628 rhinovirus, human, 28 quazodine, 476 rhodanine, PPAR, 67, 301 quetiapine, 539 rimonabant, 297 quifaplon, 398 ripazepam, 621 quinacrine, 441 risotilide, 46 quinacrine, 521 ritolukast, 447 quinapril, 250 rizatriptan, 392 quinethazone, 484 rofecoxib, 261 quinine, 325, 440, 443 rofluminast, 84 Quinhao, malaria, 470 rogletimide, 339 quinoline, antimarials, 441 rolodine, 587 SUBJECT INDEX 647 romazerit, 263 skin disease, psoralen, 431 ronidazole, 270 PUVA, 431 rotigotine, 105 retinoids, 99 RU-486, 12, 137 skin patch formulation, 104 rupinavir, 28 sleep, 589 smoking, withdrawal, 497 salivation, 336 sodium-potassium pump, gastric acid, 413 salmeterol, 49 solabegron, 51 sanfetrinem, 557 solifenacin, 452 santoquine, 442 sorbinil, 438 saponin, 121 sorbitol, 437 saprisartan, 286, 388 sorivudine, 349 saquinovir, 22 sotalol, 45 SAR, ACE inhibitors, 246 soterenol, 48 benzodiazepines, 503 soybean oil, steroids from, 122 COX-2 inhibitor, 259 spiradoline, 235 meperidine series, 228 spirapril, 248 NSAID, 71, 75, 262 spironolactone, 154 profens, 385 stanazole, 145 quinolone antibacterials, 455 statin 245, 400 sulfonamide hypoglycemics, 66, statin, 244 67, 312 statine, 20 saralasin, 284 stavudine, 353 schistosmiasis, 450, 527 stenbolone, 148 secalciferol, 187 steric bulk, 179 selective serotonin reuptake inhibitors, steric bulk, 43, 89 (see SSRI) steroids, biogenesis, 119 selodenson, 604 numbering, 120 semaxanib, 402 oxygenation at C11, 133 seminal fluid, prostaglandin source, 2 structure determination, 119 seratrodast, 83 total synthesis, 124 serendipity, 45, 54, 267, 499 stigmasterol, 122 sertindole, 396 stimulant, respiratory, 433 sertraline, 103 stroke, NMDA in cell death, 97 serum esterase, 55 structure activity relationships (see SAR) sezolamide, 586 requirements, SSRI, 59, 60 Sharpless, oxidation, 53 mistaken, 500 sialidase, 320 substituents, unnatural, 376 side effects, a-adrenergic blockers success, limited, 432 antidepressant, 371 sudoxicam, 488 cortioids, 170 sufentanil, 232 dopamine blockers, 537 sugar surrogates, 605 dopamine, 370 sulbactam, 551 tryclic antidepressants sulconazole, 274 vasodilator, 342 sulfa drugs, mode of action, 61 sulfa drugs, 63 sulfanilamide, 62, 488 sidefanil, 358, 599 discovery, 61 sitafloxacin, 460 sulfasalazine, 62 sitosterol, 122 sulfinpyrazone, 297 648 SUBJECT INDEX sulfonamide hypoglycemics, mode tetrydamine, 408 of action, 65 tezacytabine, 351 antibacterial structural requirements, 62 thalidomide, 340 sulindac, 91 thalium, toxicity, 76 sulopenem, 557 thebaine, 216 sultroban, 71 theobromine, 596 sumarotene, 99 theophylline, 593, 594 sumatriptan, 391 thiabendazole, 414, 416 sunepitron, 618 thiazides, potassium loss, 365 sunitinib, 403 thienamycin, 552 suximide, 257 thiethylperazine, 534 swoop, one fell, 12 thiobarbiturates, 364 synephrine, 56 thiothixine, 529 synthesis, enantioselective, 21, 46, 52, Third World, schistosomiasis, 450 57, 58, 78, 92, 126, 209, 244, 246, thozalinone, 264 253, 313, 322, 336, 375, 392, 438, thromboxane, 8, 18, 319 451, 470, 554, 570, 585, 597 binding site competitor, 70 b-blockers, 54 thrombus, formation, 18, 30 morphinan, 220 thyroxin, elevated levels, 356 Torgov-Smith, 124, 131 tiacrilast, 483 tiagabine, 337 tacrine, 523 tiamenidine, 290 tadalafil, 629 tiapamil, 86 talabostat, 252 tiaramide, 423 taltobulin, 35 tibecasone, 183 taludipine, 333 ticarcillin, 549 tametraline, 103 ticlopidine, 583 tamibarotene, 100 ticolubant, 326 tamoxifen, 197 tigestol, 130 tampramine, 541 timolol, 299, 312 tandospirone, 374 tiopinac, 530 tandutinib, 481 tiospirone, 374 targets, elusive, 191 tipifarnib, 452 taxol, 34 tiprednisone, 186 tazobactam, 552, 567 tirapazamine, 488 tazolol, 300 tixanox, 517 tazomeline, 329 tobacco, withdrawal, 497 tebuquine, 442 tolazemide, 65 tecadenoson, 604 tolazoline, 288 temocillin, 550, 569 tolbutamide, 65 tenidap, 402 tolciclate, 95 terlakiren, 20 tolimidone, 359 terpenes, 119 tolindate, 95 tesicam, 467 tolmetin, 242 testosterone, 141 tolnaftate, 95 tetrabenazine, 464 tolvaptan, 499 tetrahydrocanabinol, 435 topical corticoids, 182 tetramisole, 579 topixantrone, 540 tetroxyprim, 347 topoisomerases, 454 SUBJECT INDEX 649 topological analogues, 102 vasoconstrictor, 246, 253 topology, DNA, 454 vasodilator, 341, 357, 422, 489 torcetrapib, 451 vasodilator, coronary, 430 toremifene, 200 vasodilitation, by PGI, 9 transcription, DNA, 454 vasopressin, 498, 511 transition state, protease, 19 velnacrine, 523 trazodone, 371 verapamil, 85, 329 trepipam, 495 verlukast, 447, 483 treprostinil, 12 verophylline, 595 tretinoin, 35 vidagliptin, 251 triafungin, 618 vinca alkaloids, 34 triamcinolone, 180 Vioxxw, 261 triampyzine, 366 virion, DNA an/or RNA, 348 triamterine, 619 extrusion, 320 trianisene, 194 host cell, 348 triazolam, 505 replication, 348 triazolam, 621 structure, 348 trichomonas, 269 virus, replication, 19, 320 trifenagrel, 279 Vitamin D, 429 triflupromazine, 535 bone structure, 186 trimazocin, 478 hydroxylation, 187 trimethadione, 266 skin growth, 188 trimethoprim, 346 VLDL, very low density trimethoquinol, 465 lipoproteins, 451 trimetrexate, 481 voriconazole, 307 trioxifene, 202 vorozole, 425 trioxsalen, 431 triptan, migraine drugs, 391–394 WARF, 429 troglitazone, 302 warfarin, 429 troxacitabine, 354 weekly dosing, 443 tuberculosis, 267, 268, 323, 364 world travelers, 228 tubulin, cell division, 34 tumor necrosis factor, (TNF), 340, 406 xanomeline, 329 tumors, blood vessels, 402 xanoxate sodium, 516 turosteride, 152 xanthine oxidase, 304, 601 xanthine, 597, 602 ulcerative colitis, 62 xemilofiban, 33 ulcers, NSAID induced, 14 x-ray structure and drug uldazepam, 505 design, 22 upper, 264 xylometazoline, 288 uridine, 348 yam root, steroids from, 121 valdecoxib, 260 Valliumw, 501 zafirlukast, 398 vapiprost, 18 zalcitabine, 352 vardenafil, 600 zalepon, 589 varenicline, 498 zanamivir, 321 varespladib, 397 zankiren, 21 vasoconstriction, 56, 287 zanoterone, 146 650 SUBJECT INDEX zenarestat, 485 zolazepam, 621 zidovudine, 350 zolmitripatan, 392 , 258 zolpidem, 500 zindotrine, 609 zometapine, 620 zinoconazole, 275 zompirac, 243 ziprasidone, 404 zoniclezole, 421