Index

Symbols β-Adrenoreceptor-blocking drugs (–)-Pseudoephedrine 53 403 (-) 3S, 4R-Enantiomer of α-Adrenergic 305 β- 384 cromakalim 890 α-Adrenergic blocking activity β-Antagonist 391 (-) Bromhexine hydrochloride 390 β-Blockers 364, 882, 889 566 α-Adrenergic Blocking Drugs β (BIC) 827 344 -Halo-arylamines 34 β (DIC) 827 α-Adrenoceptor Blocking Agents -Ketoacidosis 669 (MIC) 827 388, 389 β-Lactam antibiotics 737 (R) and (S) Isomers of ampheta- α β-Lactam inhibitors 751 -Adrenoreceptor antagonists mine 270 388 β-Lactam ring 743 (R)-Amphetamine 270 α-Designation 865 β-Lactamase 748, 750, 758, (S) – (+) sodium 52 α-Eucaine 140, 141 759, 762 (Z)-Isomer 514 α-Glucosidase inhibitors β-Lactamase activity 760 β [D-Ala2, D-Leu5] enkephalin 672, 682 -Dimethylcysteine 738 310 α β -Glycosidase as a substrate 683 -Lactam structure 741 1, 3-Diaminoinositol 789 α β -Methylnorepinephrine 354 -Lactamase combinations 751 11-Hydroxy CPZ 846 α β - 548, 549 -Lactamase producers 751 11β-Hydroxysteroid α-Adrenerging blocking drugs β-Lactamase-producing Gram- dehydrogenase 722 367 negative organisms 758 14C-Labelled substrate 782 α -Lipoproteins 868 β-Lactams 742, 761 16β-Hydroxy-17β-estradiol 705 α -Prodine 548 β-Lipoproteins 868 17-Hydroxy-CPZ 846 α β 1-Adrenoreceptors 388 -Naphthyl salicylate 281 17β-Estradiol 688, 705 α β 1-Agonist 384 -Receptor-blocking pharmaco- 197Hg isotope 443 α logical characteristic 2-Adrenergic receptors 354 2, 3-Diphosphoglycerate (DPG) α features 384 analogues 71 2-Adrenoreceptors 388 α β-Receptors 55, 384 2, 5A Synthetase 857 2-Agonist activity 354 α β-Solamarine 825, 826 2-Deoxystreptamine 789 2- 391 α β-Substituting groups 687 2-Hydroxy-5-nitrobenzyl chloride 2-Globulin 349 α β-Tubulin 657 618 2-Receptors 388 β1 and β agents 386 2-Hydroxyestrone 705 17α-Hydroxyestrone 705 2 β β-Adrenergic activity 387 1-Partial agonist 398 2-Log-drug 800 β β-Adrenergic agonist 884 2-Adrenergic stimulant 54 2-Methoxyestrone 705 β β-Adrenergic blocking drugs 344 2-Agonist 387 2-Nitroaniline 24, 25 β 2D Display coordinates 67 β- agonists 2-Receptors 387 386 β2-Selective bronchodilator 387 3, 4, 5-Trimethoxybenzaldehyde 643 β-Adrenergic receptors 371 3, 4, 5-trimethoxy benzoid acid 3, 4-Dihydroxyphenylalanine β-Adrenoceptor Blocking Agents 838 (DOPA) 431 391 (–) 3S, 4R Cromakalin 890 3, 4-Dihydroxyphenylethylamine β (–)-Ephedrine 53 -Adrenoreceptor antagonist 889 431 897 898 MEDICINAL CHEMISTRY

3-Bromo-4 (hexylamino)-N- 4-Log drug 799, 800 7-Log combination 800 hexyl-1, 894 4-Phenylpiperidine analogues 8-Naphthalimide 894 3-Diethylamino propyl ester of 3, 322 8-Amino quinoline structural 4, 5-Trimethoxy 838 4′-Hydroxy analogues 632 3-Log drug 799, 800 glucuronide 533 8-Aminoquinoline 637 3-Quinoline carboxylic acid 786 5, 5-Diphenylhydantoin 216 8-Aminoquinoline analogues 623 3, 4-Dihydroxyhexylethylamone 5, 5-Diphenylhydantoin sodium 9-Aminoacridines 632 431 220 99 mTc 889 11β-Hydroxysteroid 5α-Cholestane 689 dehydrogenase 722 A 5-CH3 hydroxylation 518 3-Tubulin 657 5-Ethyl-5-phenylhydantoin 220 A-Type compounds 865 3D Chemical databses 74 5-Fluorodeoxyuridine-5′- Aberrant calcium signalling 219 3D Contour map 73 monophosphate Abnormal synchronous discharg- 3D Database from chemical (FUMP) 816 ing 218 abstracts 74 5-Fluorouracil from uracil 47 Absence seizures 219, 220 3D Database searching methods 5-Fluorouracil 47 Absolute configuration 55 79 5-Hydroxytryptamine 89 Absorption, distribution, metabo- 3D Databases 74 5α-Pregnane 688 lism and excretion (ADME) 3D Isoptential contour map 89 5α-Androst-8-ene 688 22, 90, 91 3D Search 75 5-Substituted hydantoins 216 Acarbose 682 3D Structure 60 5′, 3′-Phosphodiester bond 892 ACE inhibitors 87, 88, 889 3D Structure of macromolecular 5α, 8α-Androstane 689 Acetamido functional moiety targets 66 5α-Androst-8(14)-ene 688 396 3D Structure of macromolecular 5α-DHT 696 Acetaminophen 276, 274, 275, targets 66 297, 300, 298 5α-Dihydrotestosterone 696 3D Transformed ‘world coordi- Acetophentidine 274 5α-Estrane 688 nates’ 67 Acetanilid 299 5α-Reductase 697 3D-Databases 73, 74 5, 274, 276, 278, 5β-Androstane 688, 689 3D-Databases of ligands 76 279, 298, 585, 656 5β-Pregnane-3α-20α-diol(I) 709 3D-Orientation 50 Acetazolamide 457, 458, 3D-QSAR 88 6-Deoxy-6-demethyltetracycline 459, 461 ′ 776 4, 4 -Diaminodiphenyl sulfone Acetohexamide 673 644 6-Deoxy-6- Acetyl 15, 284 4-Aminoquinoline analogues methylenetetracyclines 776 Acetyl sulphafurazole 597 614, 632 6-Hydroxytryptamine 89 4-Aminoquinoline counterparts 6-Keto-prostaglandin F1α 10, 16, 16, 623 42, 156, 245, 399, 399, (6-oxo-prostaglandin F1α) 424 4-Aminoquinoline drugs 622 867 Acetylcholine chloride 403, 4-Aminoquinolines 623, 636, 6α-Hydroxytestosterone 696 637 400, 399 6-Mercaptopurine 814 4-Hydroxy cyclophosphamide Acetylcholinesterase 407 7-ACA 754, 755 804 Acetylcystein 566 7-Aminocephalosporanic acid 4-Hydroxyestrone 705 755, 754 Acetylcysteine 568 INDEX 899

Acetylsalicylic acid 15 Adipate 654 AIDS-vaccines 891, 894 Acrylic 218 Adjuvant therapy 541 Al-Mg-antacids 785 Aciclovir 858 Adrenal cortex 718 Albendazole 655, 656, 657 Acid (DNA) 854 Adrenal cortical hormones 686 Albuterol 386, 387 Acidotic diuretics 477 Administered antineoplasmic 227, 232 Acquired immunodeficiency drug 798 Aldol condensation 142, 263 syndrome (AIDS) 890 Adrenoreceptor antagonists 388 Aldophosphamide 804 Acriquine 637 Adrenoceptor blocking agents Aldosterone 471, 472, 718, Acrivastine 509 388 873 ACTH 472 Adrenergic stimulant 54 Aldosterone antagonists 872 Actinomycin C 818 Adreno-receptor blocking drugs Aldosterone titer values 720 Actinomycin D 818 403 Aldosterone inhibitors 471 Action potential 219 Adrenal cortical 718 Algorithm 73 β Adrenal corticoids 730 Activation of 1-receptors 384 503 Active benzoyl ecognine 129 Adrenal steroids 537 Alkali therapy 598 Active cavity 69 Adrenaline 376 823, 837 Active conformers 93 Adrenaline 147, Alkylating agents 801 374, 375, 376, 385 Active drug 466, 220 Alkylating antineoplastics 800 Adrenergic 375 Active metabolite 220, 300, Alkylene diols 839 Adrenergic blocking profile 34 367, 480, 507, 583, Allobarbital 179 Adrenergic neuron blockers 375 816, 860 Allopurinol 539, 541, 813 Adrenergic neuron blocking Active metabolite FUMP 816 Allosteric sites 71 agents 431 Active site 69, 73, 76, 83 Aloprostadil 866 Adrenergic receptors 55 Active site for a target molecule Alpha-adrenoceptor 389 69 Adrenocortical steroids Alpha-shape method 69 Active steroids 696 718, 720, 732 Alprostadil 866, 867 Actual receptor mapping 88 Adrenocorticosteroids 830 Alternative drug 761, 775, 790 Acute myocardial infarction 337 Adrenocorticotropic hormone (ACTH) 472 Althiazide 454, 455 Acyclic tertiary amines 821 Adriamycin 827 Altizide 445, 454, 455 Acyclovir 857, 858, 859, 860 Advanced molecular graphics 70 Al-Mg antacids 785 Acyclovir 860 Aedes aegypti mosquito 613 553, 560 Acylamino-propanediol chain Amantadine hydrochloride 556, 771 Age Incidence 795 560, 561, 855 Addison’s disease 696 Agents 386 Amantadinum 855 Adenine 814 Aglycones 710 Amantidine 856 Adenine deaminase 860 Agonists/antagonists 335 AIDS 890, 891, 892, 893, 894 Amantidine hydrochloride Adenocarcinoma strains 818 855, 856 Adenosine 255 AIDS immunoglobulin prepara- tions 893 Amaryllidaceae alkaloids 821 Adenosine triphosphate (ATP) Amaryllidaceae group of alka- 658 AIDS-Immunoglobulins 891, 893 loids 820 Adenylate cyclase stimulants 884 AIDS-related complex (ARC) Amethocaine 164 Adenylate cylase activity 312 891, 892, 893 900 MEDICINAL CHEMISTRY

Amethocaine hydrochloride 135 Amodiaquine iminoquinone 622 -antipyretic 275 AMI-H-atom abstraction 91 Amoxicillin trihydrate 753 Anhydrotetracycline 774 Amidase enzymes 676 Amorphous zinc-insulin compo- ANS 374 Amidopyrine 288, 289 nent 670 Antagonists 335 Amikacin 761, 785 Amoxicillin 749, 753 Angiotensinogen 349 Amino Acid Antagonists 817, AMPA 219, 268 325 811 Amphetamine 255 Anileridine hydrochloride 322, Aminoacetaldehyde 739 Amphetamine-type hallucino- 325, 326, 338 Aminoacetyl-t-RNA 789 genic drugs 7 Aniline 277, 286 Aminoacrichin 636, 637 Amphetamines 254, 270 Aniline and p-Aminophenol Aminoadipyl side-chain 754 Ampicillin 748, 749, analogues 275 Aminoalcohol 425 753, 756, 770 Aniline-based analgesic-antipy- Aminoalcohol carbamates Ampicillin-resistant strains 758 retic 275 416, 424 Amrinone 883, 884 Anodynes 566 Aminoalcohol esters 409, 423 Amylobarbitone 180 Anopheles mosquito 613 Aminoalcohol ethers 416, 424 Amylocaine 131 497 Aminoalcohols 417, 425 An 308 Antazoline hydrochloride 497, Aminoalkylethers 485, 486, Anabolic activity 696 498, 500 560, 514 Anaesthesia 106 Anthelmintic 654 Aminoamides 425 Anaesthesiophoric moiety Anthelmintics Aminoglycosides 789, 790, 791 129, 155 652, 653, 654, 661 Aminometradine 474 Anaesthetic ether 107 Anthracyclines 819 Aminopenicillin oral prodrug Anaesthetist 247 Anti-muscarinic agents 408 749 Analeptics 256, 260 Anti-psychotics 304 Aminopenicillins 748 Analgesic 305, 579 Anti-UV erythema 301 288, 542 Analgesic activity 579 Antiabsence activity 221 Aminophylline 256, Analgesic drugs 297 Antiandrogens 871 258, 259, 269 Antiasthamatics 867 Aminopterin 47 275 Antibacterial activity 754, 791 Aminopyrine 288, 289, 300, Analogues 3 Antibacterial agent 644 542 Analogues of purines 811, 813 Aminosalicylic acid 785 Analogues of pyrimidines Antibiotic 736, 788, 818 Amiodarone 365, 366, 364 811, 815 Antibiotic resistant bacteria 737 Amisometradine 474 Androgen receptors 871 Antibiotics 737, 751, Ammobarbital 199 Androgenic activity 696 784, 789, 817 Ammonium chloride 477, Androgens 691, 691, 692, 718, Antibradykinin activities 301 478, 568, 569, 570 870 409 Amobarbital 54, 180, 181, 179 Androsterone 691, 692, 696 Anticholinergic activity 848 Amodiaquine 614, 617, 622 Angiotensin-converting enzyme Anticholinesterase 245, 344 Amodiaquine hydrochloride inhibitors 86, 889 Anticholinesterase drugs 617, 622 Angiotensin II receptor 349 399, 403 Amodiaquine toxicity 622 Angiotensin II receptor antago- Anticonvulsant drugs 205 Amodiaquine base 619, 620 nists 349 Anticonvulsants 204, 209, INDEX 901

215, 217, 218 Antineoplastic agents 794, 795, Arabinosyl hypoxanthine (ara– Antidepressants 509 797, 800, 801, 802, 809, HX) 860 Antihormone diuretics 471 812, 817, 827, 832 Arachidonic acid casade 602 Antidysrhythmic drugs 355 Antineoplastic drug 47, 798, Arildone 860, 861 799 Antiepileptic drugs 204 Arrest cell growth 829 Antineoplastic profile 832 Antiestrogens 870 Artemether 646, 647 Antiparkinsonism 417 Antifibrillatory drugs 355 Artemisinin 646, 647, 648 Antiparkinsonism agent 417, Antifolic acid compounds 811 Artemisinin prodrug 648 420, 425, 549, 553 Antifolics 811 Artemotil 646, 647 Antiparkinsonism drug 552, 556 Antigen 655, 887 Artesunate 646, 647 Antipodes 50 Antigenic assays 782 Artimisinine 613 Antiprogestational steroids 874 Antihistamine 484 Arylacetamide 308 Antipsychotics 304, 556, 836, Arylacetic acid analogues 527 Antihistaminic action 499 837, 844 Aryloxypropanolamines Antihistaminic agent 492, 497 Antipyretic 274, 296 394, 395 Antihistaminic activity 843 Antipyretic analgesics 5, 274, Arylpropionic acid analogues Antihistaminics 45, 484, 296, 297, 542 530 485, 504, 510 Antipyretic–analgesic activity 15 Ascomycetes 725 Antileprotic drugs 876 Antipyretics 297 Asparaginase 828, 829 Antileukemic activity of mustard Antipyrine 287, 299 gas 801 Asparagine 798 Antirachitic vitamins (Vitamin D) 15, 275, 278, 279, 280, Antilipedemic drugs 865, 868 686 281, 283, 284, 298, 299, Antilipemic drugs 867 Antirheumatic drug 5 300, 301, 542 Antimalarial agents 538, 614 Antiseizure drugs 204 506, 507, 508, 509 Antimalarial drug 628, 642 Antisympathetic drugs 363 AT III 887 Antimalarial vaccine 613 Antithyroid activity 876 Atom centered dipole 65 Antimalarials 612, Antithyroid drugs 865, 874 613, 654, 661 Atom centered monopole 65 Antitubercular antibiotics 877 Antimetabolite of thymidine 858 Atom centered quadrupole 65 Antitubercular chemotherapy Atom to atom linkage 90 Antimetabolites 811, 829 877 Atom-gap distance 73 Antimicrobial drugs 782, 783 Antitubercular drugs 876, 877 Atropine 3, 228, 344, 408, 409, Antimuscarinic 408 Antituberculostatic activity 881 411, 412, 424, 553, Antimuscarinic agents 408, 409 Antitumour agents 819 560, 843 Antimuscarinic 412 Antitussive property 579 Atropine-type compounds 424 Antimuscarinic drugs 344, 416, Antitussives 566, 579 553 Auranfin 535 Antitussive agents 568, 573 Antimycobacterial agents 790 Auranofin 535, 537 Aryltrioxanes 648 Antimycobacterial drug 783, Aurothioglucanide 536 Atromid-S, 869 784, 788, 865, 876 Aurothioglucose 535, 536, 537 Antiviral activity 860 Antineoplastic effects 815 Aureolic acid 825 Antiviral drug 855, 856, 857 Antineoplastic activity 827 Aviado’s hypothesis 567 Ara-C 829 Antipseudomonal penicillins 750 ASC 586 902 MEDICINAL CHEMISTRY

ATP 658 Basal anaesthetics 106, 116 Benzylpenicillin 737 Aureomycin 772 Base molecule 92 Betamethasone 522, 728, 730, Aurothioglucose 535 Basic entity 160 731 Aurothioglycanide 535, 538 Beef tapeworm 653 Bethanechol chloride 399, 400, Autonomic drug 344, 374 Belladona alkaloids 425, 843 403 Autonomic drugs 374 Bemegride 260, 263, 264, 270 432, 433 Autonomic nervous system Benactyzine 840, 842, 843 Bethanidine sulphate 431, 432, 433 (ANS) 374 Benactyzine hydrochloride 842, Auxin 85 843 Bethanidine sulphate 431 Azacrin 637 Bendrofluazide 448 Betol 281 Azacyclonal 840 Bendroflumethiazide Biguanides 642 Azaserine 817 445, 448, 454 Bile acids 686, 690, 713 Azaspirodecanediones 850 284, 542 Binding affinity 81, 99 Azathiopurine 813, 814 Benorylate 284, 300 Binding affinity profile 99 Azidothymidine 891 Benzamine hydrochloride 140, Binding ligand 73 Azithromycin 784 141, 142 Binding of ligands to enzymes 71 Azosemide 470 Benzatropine 556 Binding phenomenon 80 AZT 892 Benzene disulphonamide struc- tural analogues 455 Binding pockets 79 AZT-monophosphate 892 Benzhexol hydrochloride 551 Binding-energy 76 AZT-triphosphate 892 Benzhydryl functional rings 500 Binding-energy judgement 82 B Benzimidazole anthelmintic Binding-pocket of MHC peptide drugs 659 79 Back-diffusion 298 Benzimidazoles 507, 653, 655 Binding-site cavity 97 Bacampicillin 748, 749 Benzoate 701 Binding-site hypotheses 86 Bacampicillin hydrochloride 749 Benzocaine 131, 164, 165 Binding-site models 85 244, 250 123, 191, 194, Binding-site residues 97 Bacterial dihydrofolate 195, 216, 248, 851 Bio-isosterism 45 reductases 644 Benzomorphan analogue 321 Bioactive agents 14 Bactericidal 764 Benzonatate 567, 574, 578 Bioactive entities 15 Bactericidal agent 790 Benzothiadiazine 445, 454, 462 Bioavailability 339 Bacteriostatic action 764 Benzothiadiazines 445, 454 Bioavailability of ‘digoxin’ 712 Barbital 173, 175, 206 Benzothiazide type of diuretics Biochemical constitution 782 Barbital sodium 173, 175 463 Barbitone 173 Benzothiazides 445, 454 Biochemical theory 119 Barbitone sodium 175 Benzotropine mesylate 424 BIC 827 Barbitvrate anion 198 Benzoin 207 Bioisosterism 2, 45 binding site 195 Benzil 207 Bioisosters 46 41, 123, 170, 171, Benzoyl ecognine 130 Biological activity profile 719 179, 194, 198, 199, Benzoxazole analogues 242 Biological characteristics 36 205, 217, 218, 248, Benzthiazide 445, 449, 454 Biological half-life 722, 726, 304, 843, 851, 882 Benztropine mesylate 416, 727, Barbituric acid 171, 172, 173 556, 560 INDEX 903

730, 731, 732 Bromoguanil 637 C Biological modifiers specific Bromovinyldeoxy uridine Ca2+-channel blocking activity antibodies 832 (BVDU) 860 371 Biological response 34 Brompheniramine 515 CADD 61, 90, 91, 95, 97 Biological-half life 723 Brookhaven Protein Databank CADD approaches 97 Biologically active drug 3 (PBD) 74 CADD methods 67 Biologically-active-prototypes 2, Buclizine 499 CADD techniques 98 7 Buclizine hydrochloride CADD-strategic approaches 97 Biopsy examination 800 499, 501 Caffeine 194, 255, 256, 257, Biotechnology revolution 13 Bufadienolides 882 269, 473, 474, 475 Biotransformation 2, 41, 42 Bufalin 882, 883 Calcitonin 870 Biperiden 549, 550 Bufotalin 882 Calcium 884 Biperiden hydrochloride Building blocks 80 Calcium channel blockers 889 417, 425, 549, 550, 552 Bulky and large hydrocarbon Calcium chloride 477 Biperiden ring 553 environment 246 Calcium edetate 654 Bis-amide of 3-bromo-4 Bulky substituent 27 (hexylamino)-N-hexyl-1, 8- Bumetanide 467, 468, 469 Calculation of affinity 80 naphthalimide 894 Buphenine 367, 368, 370 Cambridge Structural Database (CSD) 74 Bisguanides 672, 681 Buphenine hydrochloride 368 Cammarata correlation 56 Bleomycin 798, 827 Bupivacaine 147, 155, 164 cAMP 883, 884, 885 Blocking agent 389 Bupivacaine hydrochloride 144, Blocking factors from B-cells 147 Camphoric acid 442 799 Burmetanide 467 Camptothecin 824 Blood-brain barrier (BBB) Busalfan 806 Cancerous tumors 797 810, 819, 892 Buspirone 851, 850 305 Boforsin 885 Buspirone hydrochloride 851 Cannizzaro reaction 261 Bogert-Cook method 689 Busulfan 806, 807, 829 Canrenone 472, 873 Bonded class 61 Butacaine 136, 155, 156 Caphalosporin C 754 Brain-peptides 297 Butacaine base 136, 137 Capreomycin 785, 790, 791, 879 308, 310 Butacaine sulphate 131, 136, Capreomycin IA 790 tosilate 365 137, 164 Capreomycin sulfate 877, 879 Bretylium tosylate 364, Butamben 131, 132 CAMM 345 365, 366 Butobarbitone 179, 180 CA 456 Bridging fragments 76 320 Cajeputol 573 487 Butorphanol tartrate 317, Capreomycin IB Bromhexine 569 320, 337 Capreomycin-resistant strains Bromhexine hydrochloride Butyl aminobenzoate 132 791 568, 569, 570 Butyrophenone antipsychotic Captodiame 840, 841 Bromine-containing dyes 894 drugs 505 Captodiame hydrochloride Bromocriptine 553 Butyrophenones 849 841, 843 Bromodiphenhydramine hydro- Butyrylcholinesterase 407 Captropril 87 chloride 487, 490 399, 401, 403 Bromodiphenylmethane 557 214, 215 904 MEDICINAL CHEMISTRY

Carbamylation 248 Catharsis 652 Centrally acting antitussive Carbapenems 790 Cationic nitrogens 246 agents 573 Carbapentane 578 Cationic zones 246 Centrally acting antitussives 566 Carbenicillin (I) 751 Caudal anaesthesia 129 Centrally acting muscule relax- Carbetapentane 579 Causation of neoplasms 794 ants 235, 246 Carbetapentane citrate 567, 574, Cavity 73 Cephalexin 755, 756, 757 575, 576, 578 Cavity-pocket interface 73 Cephalexin molecule 757 Carbidopa 561 Cavity-pocket interface lattice Cephaloglycin 757 Carbinoxamines 501 points 74 Cephaloridine 757 Carbohydrate-regulating 718 CD4+ and CD8+ T-cells 613 Cephalosporin 737, 755, 758, Carbon dioxide 739 Cefamandole 758, 759, 760 759 Carbonic anhydrase (CA) 456 Cefamandole nafate 758 Cephalosporin C 754, 755 Carbonic anhydrase inhibitor Cefazolin 755, 756 Cephalothin 757 462 Cefazolin sodium 755, 756 Cephradine 755 Carbonic anhydrase inhibitors Cefepime 763 Ceptradine 757 456 Cefepime hydrochloride 763 Cerebrospinal fluid (CSF) 760, 788, 810 Carbovir 891, 892, 893 Cefixime 760 Cessation 65 Carbromal 193 Cefotaxime 760, 763 Cestodes 653 Cardenolides 882 Cefoxitin 758 Cardiac β -receptors 396 Cestrinone 874 1 Cefoxitin sodium 759 Cetohexamide 673 Cardiac glycosides 345, 346, Ceftazidime 760, 762, 763 686, 690, 709, 882 Channel receptor 160 Ceftazidime sodium 761 Cardiac steroids 882 Chappel and Seemann’s hypoth- Ceftibuten 762, 760 Cardiac steroids and related esis 567 Ceftoxime 763 inotropic drugs 865, 882 Characterization of site 72 Cefuroxime 758, 760 Cardiovascular diseases 889 Charge-charge interactions 63 Cefuroxime sodium 759 Cardiovascular drugs 344 Charge-dipole interactions 62 95 238, 239, 240, CHEM-X 75 CBM 310 249 Chemical diversity of products Carmustine 808, 809, 810 Cell-cycle specificity 796 92 Cardiostimulants 367 Cell-cycle-phase 797 Chemical manipulation 4 Carrier protein 881 Cell-life cycle 796 Chemical reactions of the Carnenone 472 Cellular DNA polymerase 859 penicillins 743 Catechol 377 Cellular thymidine kinase 892 Chemistry of aminoglycosides Catechol-o-methyltransferase Central antipyretic mechanism 789 (COMT) 54, 384 297 Chemotherapeutic consideration Catecholamine 255, 270, 384, (CNS) 608 431, 839 121, 226, 254, 770 Chemotherapeutic intervention Catecholamine accumulation 839 Central nervous system (CNS) 796 stimulants 254 Chemotherapy of epilepsy 216 Catecholamine dopamine 431 Central sympathomimetic agent Chenodeoxycholic acid 712, Catecholamine synthesis 561 255 713 Catharanthine 821 Centrally acting α2-agonists 391 Chiral centre 120, 632 INDEX 905

Chiral compounds 50 citrate 496, 497 Chronotropic effect 269 Chirality in ofloxacin 786 Chlorothiazide 445, 446, 447, Chrysanthemic and pyrethric Chlopromazine 848 449, 450, 451, 452, 454, acids 663 Chloral hydrate 193 455, 461, 462 Chrysanthemum 663 Chlorambucil Chlorphenamine 512 Chrysanthemum extract 663 801, 804, 805, 806 Chlorphenamine maleate 512 Ciclacillin 753 Chloramphenicol 767, 768, Chlorphenesin 237 Cimetidine 516, 517 769, 770, 771, 882 Cinchocaine 149, 165 Chloramphenicol base 770 236, 237, 249 Cinchocaine hydrochloride 149 Chloramphenicol palmitate (USP) Chlorpheniramine maleate Cinchonidine 613, 614 3, 771 512, 514 Cinchonine 613, 614 498 558 Cinchophen 285, 286, 287, 299 Chlorcyclizine hydrochloride Chlorphenoxamine hydrochloride Cineole 572, 573 498, 499, 500 416, 424, 556, 558, 561 Cinerolone 663 Chlorguanide 640 Chlorphensin carbamate 249 Cinnamonitrile 643 Chlorguanide hydrochloride 638, Chlorproguanil 637 640 Cinoxacin 785 Chlorpromazine 555, 556, Chloride channel 123, 195 Ciprofloxacin 785, 786, 560, 843, 844, 846, 849 Chlormadinone 872 787, 788 Chlorpromazine hydrochloride Ciprofloxacin hydrochloride Chlormadinone acetate 872 846 monohydrate 788 Chlormerodrin 439, 440, 443 Chlorpropamide 673, 674 Ciprofloxacine hydrochloride Chlormerodrin (197 Hg) 439, Chlortalidone 464 440, 443 787 Chlortetracycline 3, 772, 776 Chloro functional moieties 392 cis-diethylstilbesterol 43, 49, 48 Chlorthalidone 462, 464, 466 Chloroacetyl catechol 378 cis-trans isomerism 7 242, 243, 249 Chlorobenzene 277 Cisplatin 826, 827, 828 Cholestanol 690 Chlorocyclizine 499 Chrysene 687 Chrysanthemic acid 663 Citrate 654 Chloroethane 31 Cholesterol 690, 693, 712, 868, Clarithromycin 784 Chloroform 111, 123 869 Class I anti-arrhythmic drugs 367 Chloropheniramine 515 Cholestyramine resins 712 Class II anti-arrhythmic drugs Chinocide 623 Cholestyramine(I) 712 367 Chloromycetin 767 Cholic acid 712, 713 Class III anti-arrhythmic drugs Chloroprocaine 157, 159 salicylate 284, 299, 367 Chloropyrilene 496 542 Class IV anti-arrhythmic drugs Chloropyrilene citrate 496, 497 409, 848 367 Chloroquine 538, 613, 614, 617, Cholinergic drugs 399 Class-III antiarrythmic agent 366 620, 621, 622, 642 400, 403 Class-III antidysrythmic drug Chloroquine base 616, 617 366 Cholinesterase inhibitors 247 Chloroquine phosphate 614, Classical bioisosteres 46, 47 Cholinolytic 409 617, 621 Classical recombinant techniques Cholinomimetic drugs 399 Chloroquine sulphate 617 195 Chromaffin granule transporters Chloroquine-resistant malaria Clauvulanic acid 751 839 643 906 MEDICINAL CHEMISTRY

Clavulanate-amoxicillin 752 Colon 720 Congeneric series 83 Clavulanate-ticarcillin 752 Color-code mode 74 Conjugation 42 Clavulanic acid sulbactam Combination chemotherapy 799 Constitutional isomers 54 tazobactam 751 Combination regimens of Contralateral 246 Clinical utility of natural antibiot- ethambutol 784 Coprostanol 690 ics 736 Combinatorial chemistry 14, 92 Corinary disease (CHD) 868 Clofazimine 790 Common denominator 217 Coronary artery disease (CAD) Clofazimine 645, 785, 790 Common ‘world’ coordinate 868 Clofibric acid 869 system 67 Corresponding conjugates 709 214, 216, 222 Comoquine 614 Cortical collecting tubule 720 Cloned receptor 92 Comparative Molecular Field Corticosteroids 697, 718 Analysis (CoMFA) 73 350, 354 Corticosterones 692 Comparison of sulphadiazine Vs Clonidine hydrochloride 350, Corticotropin 870 sulphanilamide 594 553 Cortisol 730 Competitive antagonist 246, 472 Cloning phenomenon 84 Cortisone 688, 718, 722, 723, Cloxacillin 746, 747 Competitive neuromuscular 730, 870 Cloxacillin sodium 746, 752 blocking drugs 245 Cough centres 275 Clozapine 847, 848, 849 Competitive paralyzants 245 Cough suppressants 566 CNS stimulants 254 Complementary molecules 76 Coulomb’s Law 63 CNS stimulation 474 Complex oligosaccharide 682 Covalent-bond synthesis 14 CNS-active antihypertensive Computational chemistry 66 COX-1 95, 522 drugs 553 COMT 384 COX-2 95, 97, 522 CNS-depressant drugs 843 Computer generated graphics COX-2 based NSAIDs 97 706 CNS-depressants 304, 553 COX-2 enzyme inhibitors 101 Computer simulations in drug- CNS-drug 474 COX-2 inhibitors design 90 CNS-peptides 267 95, 96, 97, 98, 99, 100 Computer-aided drug design 61 CNS-stimulants 269 CPM 310 Computer-aided molecular Coal tar analgesics 275 CSF 788 modelling (CAMM) 345 CNS 121, 226, 254, 770, 798 CPZ 504, 560, 846, 847 Computer-aided physico-chemi- Clofibrate 869 cal methods 22 Craig plot 35, 36 Collecting tubule cells 720 Computer-generated model 90 Creosote 571 129, 130, 155, 161 Computer-generated molecular Cromakalim 865, 889, 890 Cocaine hydrochloride 129 models 90 Cromoglicic acid 515 Cocillana 568, 570 Condensation of tropic acid and Cromolyn sodium 515 304, 312, 314, 315, tropine 411 Cryptoleurine 821, 823, 824 316, 335, 336, 566, 578 Configurational changes 18 Crystal structure of a target-drug Codeine elixir 573 Coprosterol 690 molecule 77 Coffee 566 CQ 622 Crystalline profile 671 Colaspase 828 Conformational analysis 99 Crystalline zinc insulin 670 Colcemid 820 Conformational flexibility 68 Crystalline zinc-insulin compo- Colchicine 820 Conformers 93 nent 670 Colforsin 884, 885 Cut-off point 26 INDEX 907

Crystallographic techniques 65 Cyclobutylmethyl 310 sodium 243, 249 Crystalluria 609 Cyclic adenosine monophosphate DDT 613 Crystalluria formation 607, 608 883 DCI (II) 392 CTZ 455, 462, 466 Cytoplasmic glycocorticoid Dapsone 604, 605, 606, 644, Cushing’s syndrome 731 receptors 722 645 321, 320 Cycloserine 785, 788, 789, 877 Data-processing 93 Cyclic basic chain analogues Cyclosporin A 72 Database searching system 74 485, 497, 514 Cyclothiazide 445, 450, 454 Database searching techniques Cyclic diacylurea 441 Cycloxygenase-II 719 74 Cyclic polypeptide complex Cycrimine 550 Database structure 76 antibiotic 791 Cycrimine hydrochloride 549, Daughter cells 800 Cyclic ureides 171, 172 550, 553 Daunomycin 822 498 CYP-3A4 91, 509 Daunorubicin 816, 817, 818, 819 Cyclizine hydrochloride Cypionate 701 Daunorubicin hydrochloride 498, 500 307, 308 818, 819 Cyclo-butylmethyl (CBM) 310 Cyproheptadine 513 Deacetylrifampin 882 Cyclobarbital 182, 186, 187 Cyproheptadine hydrochloride Deamination 817 Cyclobarbitone 186, 187 513, 514 DEC 655 244 Cytarabine 815, 816, 817, 860 231, 233, 235 Cyclobenzaprine hydrochloride Cytochrome P450 91, 123, 787 Decamethonium bromide 233, 244, 250 Cytokines 719 235, 248 Cyclodeoxygenase (COX) 95 Cytosol estrogen 871 Decarboethoxyloratadine 508 Cycloguanil 640 Cytosol estrogen receptors 871 Decisive functional moiety 50 Cycloguanil embonate 637, 639 Cytotoxic T lymphocytes 857 Defective viral particles 859 Cycloguanil pamoate 639, 640 Definite relevant complex 71 D Cyclomethycaine 137 Degeneration of microfilaria in Cyclomethycaine base 138 D-Erythro isomer 771 uterio 663 Cyclomethycaine sulfate 137 D-(–) ampicillin 749 Deglycyrrhizinised liquorice 570 Cyclomethycaine sulphate 137, D-β 738 Degrees of freedom 82 138 [D-Pen2, D-Pen5] enkephalin 310 Delta opioid receptors 310 Cyclopentane derivative 893, D-Penicillamine Delta receptors 311 865 738, 739, 745, 746 Delta-receptor-selective peptides Cyclopenthiazide 445, 450, D-Ribose residue 767 310 451, 454 D-Threo-isomer 771 Delta-sleep-inducing peptide Cyclopentolate 412 d-Tubocurarine 227, 228, 229 (DSIP) 267 Cyclopentolate hydrochloride d-Tubucurarine 44 Demclocycline 3 412, 424, 413 Dactinomycin 819 Demecarium bromide 403, 404, Cyclopentyl ring 553 Dactinomycine 817, 818, 819 405, 407 Cyclophosphamide 801, 803, Dactiromycin 819 Demeclocycline 3, 776 804, 805, 806 227, 232 Demecoloine 820 108, 121 DADLE 310 Demecycline 776 Cyclopropylmethyl 310 Dantrolene 243 Demethylated metabolites 337 908 MEDICINAL CHEMISTRY

Demethylquinidine 362 Determinant factor 797 Dibenzazepines 218, 847 Demerol (R) 549 Detoxification 41, 817 Dibenzodiazepine derivative 848 Demulcent 569 Dexamethasone 728, 731, 522 Dibucaine base 150 Demulcent expectorants 568 Dexamphetamine 194 Dibucaine 155 Deoxoridine 857 515 Diaminopyrimidines 640 De novo design 73, 80 Dexchlorpheniramine 514 Dienoestrol dibenzoate 704 Deoxyisomer 55 Dexchlorpherniramine 515 Dibucaine hydrochloride 149, Density difference method 69 Dexpropranolol 361 150, 165 Deoxuridine 858 Dexpropranolol hydrochloride DIC 827 Deoxycholic acid 713, 712 361 Dichloro diphenyl trichloroethane Deoxycycline 776 Dextranase 682 (DDT) 613 Deoxypodophyllotoxin 824, 825 Dextro-moramid tartrate 327 Dichloro-isoprenaline [II] 392 Deoxyribonucleic acid (DNA) Dextroamphetamine 270 Dichlorphenamide 460, 462 816, 854 319, 337 529 Deoxyuridylate 812 Dextromethorphan elixir 573 Diclofenac sodium 528, 529, 530 Depolarization 219 Dextromethorphan hydrobromide Diclofenamide 457, 460 Depolarizing neuromuscular 317, 319, 337, 574, 578, 579 Dicurin procaine 443 blocking drugs 233, 245 Dextromoramid 4, 5 Dicyclomine 413 Depolarizing paralyzants 245 Dextropropoxyphen 4, 5, 328 Dicyclomine hydrochloride 413, Derivatives of estradiol 701 hydrochlo- 414, 424 Derivatives of testosterone 697 ride 327, 328, 329, 339 Dicycloverine 413 DES 706, 707 52, 55 Diel’s hydrocarbon 687, 689 837, 838, 839 331, 339 Dienestrol 702, 704, 707 Design of ligands 73 Diabetic acidosis 672 Dienoestrol 704 β Design of molecules 80 Diabetic -ketoacidosis 668 Dietary fibre 712 Designer 549 Diacetyl 335 Diethazine 425 Designing drugs 74 Diacetylmorphine hydrochloride Diethyl amino 163 Designing of ligands 73 313 Diethyl malonate 172 Designing the cardiac glycoside Diamines 420, 425 Diethylcarbamazine (DEC) 655 receptor 345 Diaminobenzophenone 658 Desipraminum 838 Diaminobenzophenone hydro- Diethylcarbamazine citrate 654 Desloratadine 508 chloride 658 Diethylstibesterol 702 Desmethyl ranitidine 518 Diamorphine 321 Diethylstilbesterol (DES) 702, Desmethylmorphine 333 Diamorphine hydrochloride 312, 703, 706 DES 706 313, 314 Difenoxin 338 Desmethylastemizole 507 Diaoxide 350 Diffusion coefficient of the drug 40 Desolvation effects 82 Diastereoisomers 50, 51, 52, 614 Digestive enzymes 668 Desolvation energies 82 851 Digitalis 345, 710, 884 Desoxycorticosterone 731 Diazoxide 352, 353, 355 Digitalis glycosides 711 Desoxycorticosterone acetate 732 Dibenzazepine analogous 847 Digitogenin 714 Digitoxigenin 347, 710 INDEX 909

Digitoxin 346, 347, 348, 710, Diphemanil metisulfate 420 Diuretics 438 711, 712, 882 Diphenhydramine 43, 486, ‘Divide and Rule’ concept in Digitoxose 346 490, 560, 561 design of ligands 75 Digoxigenin 347 Diphenhydramine hydrochloride DL-Camphene 427 Dihydroepiandrosterone 694 486, 489 DL-Dopa 559 Dihydrocodone bitartarate 316, 323 DNA 816, 854 336 Diosgenyl diacetate 708 DNA probes 782 Digoxigenin 346, 710 Diphenoxylate hydrochloride DNA viruses 859 Digoxin 346, 347, 348, 362, 322, 323, 338 DNA-dependent RNA 711, 712 Diphenyl sulfone 645 polymerase 819, 826 Dihydro-s-triazine analogue 637 Diphenylhydramine 190 DNA-synthesis 797 Dihydroartemisinin 646, 648 Diphenylmethane derivatives DNA-UV spectrum 829 315, 316, 317 840 Dobutamine 884 Dihydrocodeine phosphate 312, Diphenylmethane compounds Dopamine D 848 315 840 DOPA 431 Dihydrodigoxin 712 Diphenylmethyl piperidine group DOCK 75 structural analogous 505 Dihydrofolate reductase (DHFR) DOCK 3.5 78 811, 812 489 DOCK-Programme 75, 76 Dihydrofolate reductase (DHFR) Diphenylpyraline hydrochloride Docking 99, 101 antagonists 71 489, 490 Docking by superimposition 77 Dihydrofolate reductase inhibitor Diphenylsulfone analogues 644 Docking of a flexible ligand 76 640 Dipole-dipole attractions 163 Docking programmes 79 316 Dipole-dipole interactions 62 Dopaminergic mechanisms 270 Dihydromorphinone 308 Dipropionate 701 Dopamine 55, 56, 384, 547, 548, Dihydropteridinediphosphate Dipyrone 290, 300, 542 561, 848 607 Direct-acting sympathomimetic Dopamine agonists 553 Dihydrotestosterone 871 agent 387 Dopamine antagonists 553 488, 490 Directly acting 399 Dopamine β-hydroxylase 431 Dimeric indole alkaloids 821 Directly acting parasympa- Dimeric naphthalimide 895 thomimetic drugs 402 Dose-response curve 247 Dimeric tetrahydroisoquinolines Disjunction 8 Doxapram 260, 262, 270 821, 822 Disopyramide 358, 362 Doxapram hydrochloride 262 Dimethadione 220 Disopyramide phosphate 358, Doxorubicin 827 Dimethisoquin base 152 359 Doxylamine succinate 489, 490 Dimethisoquin hydrochloride Dispersive interactions 62 DPDPE 310 149, 151, 152 Dissociation constant 43 Drocode 315 Diosgenin 708, 714 849, 850 Dissociation constant, pKa 43, Dipeptides 761 162 Droperidol injection 117 Diperodon 148, 165 Distinct polypeptide hormone Drug 470, 655 Diperodon hydrochloride 144, 668 Drug design 2, 3, 4, 6, 55, 60, 165 Disulfamide 457, 461 61, 63, 93 Diphemanil methylsulphate Disulphamide 461, 462 Drug design through 420, 421, 425, 426 Diuretic 444, 472 conjunction 10 910 MEDICINAL CHEMISTRY

Drug design through Electron-density map 79 Enhancing bronchial secretion disjunction 8 Electron-donating moiety 29 566 Drug discovery 14, 454 Electron-withdrawing Enkephalin 84, 297, 310 Drug discovery process 14 heteroaromatic nucleus 593 Enolization 171 Drug metabolism 42 Electron-withdrawing moiety 28 Enthalpy 73 Drug metabolite 41 Electrostatic and hydrophobic Entropic effects 82 Drug receptor 45 fields 73 Entropy 101 Drug resistance 800 Electrostatic forces 163 Environmental incidence 796 Drug substance 50 Electrostatic models 64 Enzyme active site 47 Drug-drug interactions 305 Electrostatic potential 89, 98 Enzyme catalysts 246 Drug-enzyme complex 751 Elevated aldosterone 720 Enzyme cyclo-oxygenase 526 Drugs to combat AIDS 865, 890 Elimination half-life 790 Enzyme-linked immunosorbent DSIP 27, 268 Emetine 571 assays 782 DSIP/P-DSIP 268 Emotional crisis 170 Enzyme-system of the host-cell 855 d-Tubucurarine 44, 227, 228, Empirical scoring 99 229 EAA 268 Epanolol 397, 398 Dwarf tapeworm 653 ELISA 782 Ephedrine 52, 53, 254, 375, Electron microscopy 22 376, 384, 385 E Effective refractory period 357 Estradiol cypionate 701 Ecognine 130 Electrical activity 357 Estradiol enanthate 701 E and Z-isomer 53 Enanthate 701 Estradiol valerate 701 E-type compounds 865 Enantiomers 50, 51, 52, 55 Epidural anaesthesia 129 Eagle’s KB carcinoma 823 Enantiomorphs 50 Epileptic seizures 205 Easson-Stedman Theory 55 Endogenous leukocytic pyrogens Epinephnine 870 Ectoparasites 664 297 Epinephrine 166, 375, 376, 377, 384, 385, 398 Edrophonium 344, 405 Endogenous oestrogens 705 Epinine (deoxy isomer) 55 Edrophonium chloride 248, 403, Endogenous opioid 306 405 Endogenous opioid peptides 306 Epitestosterone 696 Effective inhibitor 70, 890 Endomorphin-1 307 Epoprostenol 866 Effective inhibitor of histamine- Endomorphin-2 307 Epoprostenol sodium 866, 867 induced broncho constric- Endorphins 275 Ergosterol 690, 691 tion 890 Energies of formation 65 Erythromycin 679, 712 Effects of α -Antagonism 388 Ester methyl penicilloate 741 1 Energy of deformation 61 Eicosanoid 719, 865, 867 Energy of interaction 63 Ester of ampicillin 753 Electro-cardiogram 356 Energy-based docking programs Estradiol 700, 701, 705, 706 Electro-convulsive therapy 270 78 Estradiol dehydrogenase 705 Electroencephalogram 194 Energy-grid 78 Estriol 699, 700, 705 Electroencephalography 205 Energy-grid based docking 78 Estrogens 871, 882 Electrolyte effects 720 120, 247 Estrone 698, 699, 701, 705 Electrolyte-regulating 718 Enhanced sedimentation coeffi- Etacrynic acid 467, 469 Electron withdrawing pyrimidine cient 829 Etamivan 261 nucleus 595 Enhancement in interior negativ- Ethacrynic Acid 469, 470 ity 219 INDEX 911

Ethacrynic-type drugs 470 Excitation 219 Fibrin 887 Ethambutel 877 Excitatory amino acid (EAA) Fibrinogen 887 Ethambutol 877, 784, 788 268 Filaricidal action 655 Ethambutol hydrochloride Excretion 22, 42 First generation 397 877, 880 Exogenous asparagine 829 First generation β-blockers 392, Ethambutolum 877 Expectorant 566, 568, 569, 571 396 Ethamivan 260, 261 Expectoration 566 First generation cephalosporins Ethanol 304 Exploitation of leads 3 755 Ethanolamine antihistaminic Exploration of leads 3 Falciparum malaria 621 agent 490 Expression of genes 720 First generation cephalosporins Ether 107, 247 Extended insulin zinc suspension 758

Ethical pharmaceutical industry 671 First generation H1-antagonists 12, 13 Extended-spectrum penicillins 505 ERP 357 750 First generation tricyclic Ethopropazine base 555 Extension tactics 397 antihistaminics 509 Ethionamide 877, 878, 881 Extensive intracellular binding First-administered antineoplastic drug 798 Ethionosamide 785 712 First-generation cephalosporins Ethnic incidence 795 Extrapyramidal stimulation (EPS) 755, 758 Ethopropazine 555, 556 847 First-generation H1-antagonist Ethopropazine hydrochloride F 490 425, 554, 555 First-generation H - F-type compounds 865 1 Ethosuximide 211, 212, 220, antihistaminics 490 221 Fab fragment 84 First-generation sulfonylureas False metabolite 593 Ethotoin 208, 220 673 False negatives 403 Ethoxzolamide First-line drugs 784 457, 459, 460, 462 Fast-acetylators 881 First-pass elimination 354 Ethyl chloride 121 227, 231 First-pass metabolism 337 Ethyl morphine 335 Fencarbamide 417 Fish tapeworm 653 Ethyl p-aminobenzoate 132 Fenoprofen 532 Flat worms 653 Ethylene chlorohydrin 134 Fenoprofen calcium 530, Flexible docking 79 Ethylenediamines 485, 490, 532, 533 Flow-sheet of estrogen design 9 493, 494, 500, 514 Fenoprofen glucoronide 533 Fludrocortisone 731, 732 Ethylenimines 801, 807 321, 324, 850 Fludrocortisone acetate 732 308, 310 Fentanyl citrate 117, 124, 322, 296, 301 Etidocaine 160 324, 325, 338 Flufenisal 284, 542 Etiocholanolone 696 Fentanyl citrate and droperidol Fluferisal 299 Etofyline clofibrate 868 injection 117 Flukes 653 Etofylline 256, 259 FEP determinations 99 Fluorescein 42 Eucalyptol 571, 572, 573 Ferguson’s theory 25 Fluorocortisone 727 Eugenol 152, 154 Fertilization phenomenon 663 Fluoroquinolones 784, 785, 786, Euphthalmin 140, 143 Fexofenadine 506 790 Exalgin 143 Fibric acid 869 Fluorouracil 47, 800, 815, 816 912 MEDICINAL CHEMISTRY

Fluoroxytri-fluoromethane 815 G Glimepiride 678 Fluprednisolone 728 Glipizide 676, 678 G-protein-activated K+ channel 530, 531, 532 250 Glomerular filtrate 438 Fluroquinolones 785 G-proteins 308 Glucagon 668 Flurothyl 264, 270 Glucagon secretion 676 G1-resting phase 797 Fluroxene 108, 109, 121 Glucocorticoid 718, 719, 720 G2-resting phase 797, 798 Flutamide 871, 872 GABA 123, 216, 221, 250, 255 Glucocorticoid activity 718, 723 Fluoromethane 815 GABA agonist 662 Glucocorticoid receptor 720 Flow-sheet of estrogen design 9 GABA-transaminase 221 Glucocorticoid-responsive Folic acid 48, 637 dermatoses 731 GABAA-mediated chloride ion Folate antagonists 811 conductance 123 Glucose metabolism 681 Folic acid from PABA 608 GABAergic inhibitory response Glucuronic acid 42, 876, 886 FUMP 816 123 Gating mechanism 357 For resonance structures of Gallamine 229 Glucuronide 298, 504, 705 aniline 31 Gallam 227 Glumepiride 676 Force fields 65 229, 247 Glutamine antagonists 817 Formyl acetic acid 588 Gallium-67 889 Glutathione 298 Forscolin 885 Gamma-aminobutyric acid Glutathione synthesis 800 Forskolin 885 (GABA) 216, 250 Glutethimide 170, 192, 193, Foundation 76 Ganglionic 409 199, 200 Fourth generation cephalosporins Ganglionic blocking agent 10, Glyburide 676, 677, 678 762, 763 427, 430 Glyburide 678 Fragmentation approach 79 Ganglionic-blocking drugs 348, Glycerol monoethers and ana- Free fatty acids (FFA) 868 433 logues 236 Free salicylate 299 Gastric distress 299 Glycine 255, 559 Free sulphonamide 583, 608 Gemfibrozil 868, 869 Glycolipids 782, 783 Free-energy of binding (∆∆ bind) Gene-cloning methodologies 92 Glycopyrrolate 422, 423, 553 81, 99 General anaesthetics 106, 118, Glycopyrronium bromide 420, Free-energy perturbation 97, 121, 128 422, 423, 425, 426 100, 101 General formula 687 Glycoside k–strophanthoside 882 Free-energy perturbation (FEP) Genetic change 800 Glycosides 819, 825 method 100 Genins 710 Glycosides of the Free-energy perturbation tech- Genomic DNA 782 anthracyclinones 819 nique 95 Genetic engineering 22 Glycylcyclines 777 Freshwater mollusk 653 Glycyrrhiza 568 Freshwater snail 653 Genomics 14 Glycyrrhizin 571 Friedel-Craft’s acylation 265 Geographical incidence 795 Glypizzide 677 Friedel-Craft’s reaction 469, 850 Geometrical isomers 54 G -Pool 797 Frusemide 468 Gestogens 691, 707 o Gold compounds 534 Full digitalization 712 Gi/o proteins 312 Gold sodium thiomalate 537 Full-salol principle 15 Ginger 568 Gram-positive bacterial infections Fumarate reductase 659 Gitoxigenin 710 583 Furosemide 467, 468, 470 INDEX 913

Graphical analysis 99 Heme iron 647 Higher anticholinergic profile GRID 73 Henderson-Hasselbalch equations 560 Grignard reaction 328, 840 43 Histamine 247, 484, 485, 515

Grignardization 421 Heparin 865, 886 Histamine (H2) receptor blockers Grignard’s reagent 554, 725 Heparin sodium 886 516 Histamine H -receptor antago- Growing organisms 880 Hepatic cytochrome P-450 518, 1 nists 485 Guaiacol 15, 573 679 Histamine H receptor blocking Guaicyl phenyl cinchoninate 15 HCTZ 455 2 activity 517 Guaifensin 571, 573 Hepatic cytochrome P-450 system 3A4 679 Histamine H - Guaiphensin 571 2 Hepatic drug-metabolizing 517 431, 433 enzyme system 882 Histamine mediated by H2- Guanethidine monosulphate 431, Hepatic gluconeogenesis 680 receptors 517 433 Histamine (H - & H -) receptors Hepatic metabolism 712 1 2 hydrochloride 553 484 Heroine 332 637 Histamine receptor 506 Herpes simplex virus (HSV) 894 Guanidine analogues 637 Histamine sensitive receptors Heteroarylacetic acid analogues Guanidine residues 681 484 523 Guanine 814, 829 Histaminic activity 485 Heterocycles 653 Guanine-rich DNA 826 Histidine 484 Heterocyclic amines 819, 824 Guanosine analogue 893 HIV 890, 893, 895 Heterocyclics 659 HIV centres 891 H Hexa-methonium bromide 427 HIV PR 69, 70 Hexaethyl analogue 11 H-bonding interaction 397 HIV protease 69, 71, 82 Hexafluorenium bromide 230 H-bonding sites 79 HIV reverse integrase 69 Hexafluoronium bromide 230, H and H receptors 516 1 2 227, 231 HIV reverse transcriptase 69 H -antagonism 518 1 10 HIV-1 860, 893 H -antagonists 514 1 Hexamethonium bromide HIV-drug 891 H -receptors 484 1 427, 430 HIV-drug under the spotlight Haloperidol 849, 850 Hexamethyl analogue 11 894 109, 122, 247 Hexesterol 691 HIV-immunoglobulins 893 Hammett substitution constant Hexestrol 702, 703, 707 HIV-neutralizing antibodies 893 28, 29, 32 Hexobarbital 182 HIV-vaccines 894 Hammett’s constant 33, 57 Hexoestrol 703 HLA-major histocompatibility Hansch constant 57 antigens 857 Hexylcaine 140, 157, 160 Hansch equation 33, 34, 36 Hoffmann’s degradation 265 Hexylcaine hydrochloride 131, Hansch’s correlations 33 140 Homatropine 414 HCQ 622 High presystemic elimination rate Homatropine hydrobromide 414, HDL 869 705 415 HDL levels 869 High throughput screening 92 Hookworm 652, 661 Heats of formation 65 High-ceiling diuretics 467 Hormonal antineoplastic agent 872 Hematropine hydrobromide 424 High-degree of success rate 90 Hormonal control 831 914 MEDICINAL CHEMISTRY

Hormone antagonists 865, 870, Hydrocortisone injection 722 I 874 Hydroflumethiazide 445, 447, Ibufenac 528, 529 Hormone incidence 796 448, 454 528, 530, 532 Hormone receptors 831 Hydrogen bonding 49, 76 Ideal sedative and hypnotic 170 Hormone-replacement therapy Hydrogenated 17H-cyclopenta- (HRT) 686 phenanthrene 686 Idiopathic parkinsonism 548 Hormones 830, 870 Hydrolyzable choline esters 407 Idoxuridine 857, 859, 860 HSV 895 315, 335, 566 Ifosfamide 803 HSV–1 859 Hydromorphone hydrochloride ILs-1 and -2 832 HSV–2 859 312, 315, 316, 336 Imaging radioisotopes 888 HSV-DNA polymerase 859 Hydrophilic centre 162, 163 Imaging radiopharmaceutical 888, 889 Humalog 671 Hydrophilic entity 160 IDDM 668 Human immunodeficiency virus Hydrophobic fields 73 (HIV) 890 Hydrophobic contact 76 Iletin 671 Human insulin 46 Hydrophobic optimum 40 Imidazole triazines 826, 827 Human insulin analog 671 Hydrophobic thiobarbiturate 124 Imidazoline analogue 243 Human-immune system 613 Hydroxy triamterene sulphate Imidazoline derivatives 485, 497 Hyberdised molecule 15 480 Imides and amides 819, 820 Hybridization 65 Hydroxycamptothecin 824 Immunosuppressant activity 829 Hycanthone 826, 827, 828 Hydroxychloroquine 538 Immunotherapy 831 HRT 686 Hydroxychloroquine base 620 In-built conformational freedom Hydantoin 205, 206, 216, 217, Hydroxychloroquine sulphate 85 218 619, 620, 622 Inactive anhydrotetracyclines Hydantoin analogue 218 Hydroxydione sodium succinate 774 Hydantoin counterpart 220 114, 124 Inactive ecognine 129 Hydantoin derivatives 206 Hydroxyl ion 198 Inactive isotetracyclines 774 Hydantoins 218 Hydroxyprogesterone 725 Inactive metabolites 504 Hydralazine 350, 354, 396 Hydroxyzine 840, 841 Inactive oxidative metabolite Hydralazine hydrochloride 350 Hydroxyzine hydrochloride 841, 842, 843 527 Hydrazone hydrazide 351 Hyperchromicity by DNA-UV- Inactive steroids 696 Hydrid application 65 spectrum 829 Incidence of tumours 795 Hydrochloride 754 Hyperpolarization 219 Indapamide 462, 465, 467 Hydrochlorothiazide 445, 446, Hypertension 720 Indirect action 399, 662 447, 454, 455 Hyperthyroidism 874 Indirectly acting drugs 403 316, 335, 566 Hypnotic activity 195 Indolines 465 Hydrocodone bitartrate 316, 336 Hypnotic drug 170, 175 Indomethacin 523, 524, 526, Hydrocodone tartrate 312, 316, 530, 541 317 Hypnotics 170, 194 Indoprofen 530, 532, 533 Hydrocortisone 718, 721 Hypoglycemic agents 672 Inducer of Cl– ion influx 662 Hydrocortisone 522, 718, Hypothalamic thermoregulatory centre 297 Inductive effect (F) 28, 29, 31, 722, 723, 726, 727, 870 Hypothetical receptor site(s) 155 32, 33 Gydrocortisone acetate 722 INDEX 915

Infiltration anaesthesia 129 ductance 366 Isomer epinephrine 55 Inflammatory response 820 Interferon 855, 856 Isoniazide 878 Influenza type A virus M2 Interferon α-2B 856 Isopamaquine 625 protein 562 Interferon alfa-2a recombinant Isoniazid (INH) 15, 41, 764, INH 879, 881 832 784, 788, 877, 878, 880, 881 INH-resistant strains 881 Interferon gamma 613 Isopentaquine 623, 630, Inhalation anaesthetics 106 Interferons 800, 832 631, 632 Inhibition of the synthesis of Interleukins 832 Isophane insulin 670 mycotic acids 881 Intermediate acting barbiturates Isophane insulin injection 670 Inhibitor 71 179, 190, 193 Isophane insulin suspension 670, Inhibitor of cell-wall synthesis Intermediate acting 671 788 glucocortinoid 727, 728 Isoprenaline 375, 377, 384, Inhibitor of dihydrofolate Intermediate chain 160 385, 515 reductase 642 Intermediate-acting barbiturate Isoprenaline [I] 392 Inhibitor of Na+-K+-ATPase 884 54, 190 Irritant 571 Inorganic bromides 216 Invermectin 662 Isotetracycline 774 Inorganic compounds 444 Intermediate-spectrum Isoproterenol 49 Inosinic acid 814 fluoroquinolone 787 Isoquinoline analogues 149 Inotropic drugs 345, 882 Internitrogen distance 11 Isoprenaline hydrochloride 385 Inotropic effect 269 Intraatomic distance 17 Isopropamide 417 Insulin 668, 669, 670, 675 Intracellular levels of thymidine Isopropamide iodide 417, 418, 678, 679, 680, 681, 870 triphosphate 892 419, 425 Insulin activity 670 Intramolecular distances and biological activity 42 Isopropyl functional moieties Insulin injection 670 Intravenous anaesthetics 106, 397 Insulin production 668 111, 197 Isoprotenol 49 Insulin 670 Investigative ligand 97 Isoproterenol hydrochloride 377, Insulin resistance 668 Ion channel and protein receptor 378, 384 Insulin sensitivity 681 hypotheses 121 Isosteres 44 Insulin therapy 669 Ion channels 218 Isosterism 2, 45 Insulin units 670 α Ionizable -amino moiety 761 Isosterism and bioisosterism 2 Insulin variants 672 Ionization 162 Isoxsupurine 367, 368, 371 Insulin zinc suspension 670 Ionized barbiturates 198 Isoxsupurine hydrochloride 368, Insulin-dependent diabetes Ipecac 568 mellitus (IDDM) 668 369 Iron preparations 776 Insulins 46 Isoxupurine 368 Irreversible oxidation 123 Intermediate-acting IUPAC 689 Isatin 150, 286 glucocorticoid 727 Iso-propyl cyanamide 638 J Intercellular cAMP 884 Isogramine 161 Interactive graphics 77 JG-365 83, 84, 82 Isolated groups of pancreatic Intercalation of DNA strands 636 Junctional folds 227 cells 668 Interference of colchicine 820 Isoleucine 79 Interference with calcium con- 916 MEDICINAL CHEMISTRY

K Laughing gas 111, 122 Ligand structure 69 LDL-apo β 869 Ligand-flexibility 76 Kainic acid 268 LDL-cholesterol 869 Ligand-peptide complexation 82 Kanamycin 766, 785, 790 Lead compound 37, 38, 40, 98 Ligand-receptor combinations 76 Kanamycin sulphate 766 L-cysteine 568 Ligand-receptor complex 86 Kanamycin-resistant strains 791 Lead identification 94 Ligand-receptor docking 93 Kanamycins A, B and C 767 Lead optimisation 94 Ligand-receptor recognition 68 Kanosamine entity 767 Lactam form 351 Ligand-receptor structures 68 Kappa 307 L-erythro isomer 771 Ligand-receptor volume Kappa agonists 307 Least-squares fitting 90 complementarity 75 Kappa 308 Least-squares optimization 65 Lignocaine 165, 166, 360, 361 Kappa receptor agonists 310 Leptazol 254 Lignocaine base 144 Kappa receptors 308, 337 Leslie’s method 312 Lignocaine hydrochloride 144 124 Lethal DNA damage 800 Linear free-energy approaches 7 Ketamine hydrochloride 123, Linear Hansch equation 33 112 Lethal synthesis 798, 800 metabolism 681 K+ channel 250 Leucine-enkephalin 297 Lipid theory 118 Keto-enol tautomerism 466, 172 Leukotactic substances 719 Lipoidal methylindolyl 467 Ketoconazole 679 Leukotriene synthesis 655 Lipoidal solubility 594 530, 531, 533 Levopropoxyphene base 577 Lipophilic centre 161 Ketotifen 516 Lidophilic entity 156 Lipophilic entity 156 Ketotifen fumarate 515, 516 Levarterenol 846 Lipoprotein metabolism 869 Ketprofen 532 Levodopa 553, 556, 559, 561 Lipoproteins 868 Killer (NK) cells 800 329, 339 Liquorice 568, 569, 571 Killer T-cells 799 Levopropoxyphene 576 Lispro insulin 671 Knoevnagel condensation 369 Levopropoxyphene napsylate 574, 576, 578, 579 Local anaesthetic Known ligands 70 52, 55, 340, 566 129, 132, 156, 158, 162 Known receptor 80 Levorphanol tartrate 317, 318, Local anaesthetics 128, 131, Known receptor sites 74 319, 336 132, 152, 155, 161, 163, L 147, 155, 156, 158, 164, 360 165, 166 Local hormones 865 L-(+) ampicillin 749 Lidocaine hydrochloride 144 Loci of filler atoms 73 L-1210 818 Life-cycle of the parasite 644 Löfgren’s classification 155 L-threo isomer 771 Ligand at the active site 69 Log cell survival 797 Labetalol 399 Ligand binding site 69 Log cell-kill 799 Labetalol hydrochloride 399 Ligand design 73 Log cell-kill principle 799 Lactic acid production 820 Ligand interactions 82 Logical set of components 81 Lactim-lactam tautomerization Ligand modification 71 Lomustine 808, 809, 810 196 Ligand receptor 73 Long-acting barbiturates 173, Lactones 819, 824 Ligand receptor gap region 73 728 Large structural moieties 567 Ligand receptor recognition 68 Long-acting glucocorticoid 728, Lattice of interaction energies 73 730 INDEX 917

Long-range emitters 888 Malignant tumours 797 Mefloquine 648 Longer biological half-life 594 Malonic acid 171 Mefloquine hydrochloride 648 Longer-acting mepivacaine 145 Malonic esters 171 Megestrol 830 ‘Loop’ and ‘high-ceiling’ diuret- Maltase 682 Megestrol acetate 830, 831 ics 467 Mammalian dihydrofolate Melphalan 802, 803, 805 Loop diuretics 467 reductase 644 Membrane-stabilizing agents 358 Loose dye-trytophan linkage 894 Mammalian DNA polymerase Mepacrine 633 Loratadine 508 892 Mepacrine base 635 Lorcainide 359 Mannich condensation 551, 552 Mepacrine hydrochloride 633, Lorcainide hydrochloride 359 Mannich reaction 469, 550, 635 Losartan 349, 350 577, 578 Mepacrine mesylate 636, 637 Low therapeutic index 175 Mannitol 475, 476 Meperidine 305, 318, 322, Lower antihistaminic activity MAO 547 337, 340, 549, 548 560 MAOIs 553 Meperidine hydrochloride 322, Lower mineralocorticosteroid Markownikoff’s addition 702 337 activity 718 Markownikoff’s rule 213, 410 Mephalan 801 Loxapine 847, 848 Mazindol 264, 270, 265 236, 248 Loxapine succinate 848 Macromolecular targets 66 Mephenytoin 208, 220

LTC 4 865 Malonyl urea 172 Mephobarbital 177, 206 LUDI 79 MAO 305, 843 Mepivacaine 146, 155, 165 LUDI-programme 76 MAOI 305 Mepivacaine base 146 Luteal-phase dysfunction 709 MBC-MIC ratio 787 Mepivacaine hydrochloride 144, Lysergic acid diethylamide LSD Meaning of ‘Site’ 71 146, 147 194 Mebendazole 655, 657 Mepreidine 843 M 427 238, 239, 248, Mecamylamine hydrochloride 249, 839 M-Mitosis phase 797 427, 430 Meprylcaine 157, 160

M2 channel 562 Mechanism of drug action 22 Mepyramine 491 MACCS-3D 75 Mechanism of resistance 799 Mepyramine maleate 491, 493 Macrolides 784 Mechansim of action 747 Meralluride 439, 440, 441, Mafenide 603, 604 Mechlorethamine 802 442, 443 Magestrol acetate 831 Mechlorethamine hydrochloride Mercaptan adducts 776 Major histocompatibility com- 801, 802, 805 Mercaptomerin 441 plex (MHC) 77 Mecillinam sodium 753 Mercaptomerin sodium 439, 441, Major steps in structure-based Meclizine hydrochloride 443 drug design 67 499, 500 Mercaptopurine 813, 814 Major tranquilizers 836 Meclofenamate sodium Mercaptopurinum 813 Making secretion less viscous 295, 301 Mercumatilin sodium 439 566 295 Mercurial diuretics 439 Malaria eradication programme Meclozine 499 Mercury-197 443 612 Medicinal compounds 686 Merethoxylline 443 Malaria parasite 613 294, 295, 301 918 MEDICINAL CHEMISTRY

Merethoxylline procaine 439, 170, 190, 199, Methyldihydromorphinone 335 442, 443 200 351, 354, 561 Merethoxylline procaine 439 Methazolamide 457, 458, 459, Methylnorepinephrine 354 Mersalyl 439, 443, 470 461 Methyl penicilloate 743 Mersalyl sodium 443 503 Methoxycamptothecin 824 Mesomeric effect 31 Methdilazine hydrochloride Methylphenidate 266 503, 504 Mesoridazine 847 Methylphenidate hydrochloride Mesuximide 212 Methicillin 746, 747 264, 266, 267, 270 Metabolic alkalosis 720 Methicillin sodium 747, 752 Methylphenobarbital 173, 177, Metabolic inactivation 160 Methimazole 874, 875, 876 178, 199 Metabolism 655, 41 Methionin-enkephalin 297 Methylphenobarbitone 177 Metabolism of methyprylon 200 Methisazone 860, 861 Methylpiperazine 655 Metabolism of mycobacteria 782 Methixene hydrochloride Methylprednisolone 723, 724, 420, 421, 425, 426, 553 Metabolism of sulphathiazole 725, 726 594 236, 237, 238, Methylxanthine 255 248 Metabolites 2, 123 Methyprylon 170, 193, 200 Method of disjunction 8 Metabolize GABA 216 Methyprylone 193 Method of variation 7 Metaglinides 678 Metisazone 860 Methodologies for docking 77 Metallothionine 800 Metixene 421 Methohexital sodium 113, Metaphase state 659 Metoclopramide 712 114, 190, 199 Metaraminol 379, 385 iodide 227, 228, 247 Methohexitone sodium 113 Metarminol bitartrate 375, 379, Metoformin 681 Methoin 208 380 Metoformin hydrochloride 681 Methotrexate 800, 811, 812, 238, 241, 242, 249 Metolazone 462, 465, 466 829 320 Metraminol bitartrate 385 Methotrimeprazine 327, 329, Methabarbital 205 330, 339 Metyrapone 471, 472 Methacholine 401 Methoxamine 378, 384 361 Methacholine chloride 399, 401, Methoxamine hydrochloride Mexiletine hydrochloride 360 402, 403 375, 378, 379, 385 Meyer-Overton and Meyer- 4, 5, 327, 332, 340, Methoxycamtothecin 824 Hemmi theory 24, 118 566, 567, 882 109, 110, 122 Meyer-Overton theory 119 Methadone hydrochloride Methsuximide 211, 212, 221 MHC-peptide 78 327, 339 Methyclothiazide 451, 452, 454 Michael condensation 192 Methamphetamine 255 Methyl penaldate 741 Miconazole 679 Methanesulphonate esters 806 Methyl prylon 200 Microbiological method 726 Methanesulphonate ion 806 281, 282 Microtubule synthesis 659 Methanesulphonates 801, 806 Methyl-dopa 350, 351, 352, MICs 787, 827 495 354, 553 Miglitol 682 Methaphenilene hydrochloride Methylacetanilide 143 Milrinone 883, 884 495, 497 Methylaminoacetyl catechol 377 Milrinone acetate 884 494 Methylclothiazide 445 Mineral-corticosteroid 472 Methapyrilene hydrochloride 494, 496 INDEX 919

MIC-MBC ratio 787 Molecular drug designs 246 Morphine 3, 4, 124, 300, 304, Mineralocorticoid 472, 718, Molecular dynamic simulations 307, 308, 312, 313, 314, 719, 726, 731, 732, 720 97, 101 316, 318, 319, 320, 321, Mineralocorticoid activity 718, Molecular dynamics 84 322, 332, 333, 334, 336, 337, 340, 566 723, 726 Molecular dynamics method 77 Morphine analogues 312 Mineralocorticoid-aldosterone Molecular electrostatic potential 872 (MEP) 63, 65 Morphine molecule 335 Minimal biologic profile of Molecular extensions 86 Morphine sulphate 312, 336 activity 662 Molecular geometry 65 Morphine-like drugs 304 Minimum alveolar concentration Molecular hybridisation 14 Morphine-related antagonists (MAC) 118, 119, 122 335 Molecular interaction 2 Minimum energy conformation Morpholino function 163 Molecular mechanic 69 determinations 99 Mosquito carrier 613 Minocycline 775, 776 Molecular mechanics 61, Most vital binding mode 83 Minocycline hydrochloride 775 63, 65, 66, 81, 101 Motional flexibility 78 Minor tranquilizers 836 Molecular mechanics calculations MPPP 548, 549 Minoxidil 396 100 MPTP neurotoxicity 548 Miscellaneous agents 486 Molecular mechanics methods MPTP-induced parkinsonism Miscellaneous analogues 330 95 548 Miscellaneous anti-inflammatory Molecular modeling 60, 61, 66 MPTP 548, 549 drugs 538 Molecular modeling community mRNA 722 Miscellaneous central nervous 61 Mu (µ) opioid antagonists 307 system stimulants 256, 264 Molecular modeling in drug Mu opioid activity 340 Miscellaneous sulphonamide design 89 Mu opioid receptors 307 diuretics 462 Molecular modeling software 90 Mu receptor antagonists 310 Miscellaneous theory 119 Molecular modeling techniques Mu receptors 337 Misoprostol 866, 867 61 Mucopolysaccharide 886 Misoprotol 866 Molecular orbital approach 7 Multidrug-resistant tuberculosis Mithramycin 825, 826 Molecular orbital calculations 7 789 Mitochondrial electron transport Molecule negentropy 56 Multifarious of 3D structures 85 system 636 Molecules 14 Multiple binding modes 83 Mitosis phases 797 Moniliformis 661 Mitostatic drug 798 Monoamine oxidase (MAO) Multiple binding sites 69 Mitotane 830, 831 305, 843 Multiple opioid receptors 311 Mn-neurotoxicity 547 Monoamine oxidase inhibitors Multiple-bonding sites 79 Modafinil 255 (MAOIs) 305 Muscarinic activity 391 Modeling of the site 66 Monochloracetyl chloride 377 Muscarinic agents 423 Monte carlo simulations 65 Modern chemistry 18 Muscarinic targets 403 Monte carlo technique 84 Molar refractivity (MR) 28, 31 Muscle relaxants 226, 232, 244, Molecular biology 61 Morphan analogues 320 839 Morphinan analogues 317 Molecular comparisons 89, 90 Mustards 801 Molecular connectivity approach Muzolimine 478, 479, 480 7 920 MEDICINAL CHEMISTRY

Mycobacterial strains 791 N-Arylanthranilic acid 294 Neomycin sulphate 765 Mycobacterial-catalase- Neamine 766 Neoplasms 797 peroxidase enzyme complex n-Amylpenicillin 738 Neoplasms in the CNS 798 881 Naproxen 533, 534 Neoplastic drug 799 Mycobactin M 783 Narcotine 567, 579 Neostigmine 408, 248 Mycobactin P 783 Naproxen sodium 52 Nerve block anaesthesia 129 Mycobactin S 783 Napsylate 754 Net atomic charges 64 Mycobactin synthesis 783 Narciclasine 820, 821 Neuberg’s synthetic method 376 Mycobactins 783 Narcissus 820 Neurological symptoms of AIDS 892 Mycosides 782, 783 Narcotic analgesic agents 566 Neuromuscular blocking agents Mycosterols 690 Narcotic analgesics 3, 4, 275, 304, 336, 578 227 N Narcotic antagonists 332 Neuromuscular blocking drugs 226, 227, 245, 409 N-acetylprocainamide 363 Narcotic drugs 566 Neuron firing 664 N-amylpenicillin 738 Narcotic efficacy of drugs 24 Nateglinide 679 Neuronal firing 219 N-arylanthranilic acid 294 Natural agonist 349 Neuroses 836 N-heptylpenicillin 738 Natural antineoplastic drugs 819 New antimalarial drugs 646 N-methylpiperazinyl 785 Natural avermectins 662 New chemical entities (NCEs) Na+ and K+ channels 720 14 Natural penicillamine 739 + + New fluoroquinolones 790 Na /K -activated ATPase 720 Natural penicillins 744 New leads 92 NADH-specific reduction 881 Natural products 653, 654, NADPH 606 661, 662 New target-drug 46 NADPH-dependent microsomal Natural tetracyclines 776 New target-drug-molecule 42, 46 reductases 606 Naturally occurring penicillins Nafcillin sodium 753 737 Newer drug molecules 60, 80, 83 Nalidixic acid 785 Nauseant expectorants 568 Newer drugs 90 332, 337, 340 NDMA-receptor complex 124 Newer tetracyclines 777 Nalorphine hydrochloride Ndomorphin-1 307 332, 340 Ndomorphin-2 307 Newtonian mechanics 61 307, 308, 333, Negative log of the fraction 799 Nexeridine 331, 332 334, 336, 337, 339 Negative receptor assays 871 Nexeridine hydrochloride 331 Naloxone hydrochloride 332, Nemathelminthes 652 Nicotinic depolarization 248 333, 334, 340 Necocinchophen 287 Nicotinic-receptor agonists 305 Naltiben 311 Nematode-cell division 659 NIDDM 675, 678, 680 307, 308 Nencki principle 281 Nikethamide 254, 260, Naltrindol 311 Neocinchophen 286 261, 270 Naphazoline 380, 385 Neomycin 712, 765, 766, 790 170, 191, 200 Naphazoline hydrochloride 375, Neomycine A 766 380, 381 Nitric oxide synthase 613 Neomycin B 766 Naphthalene acetic acid ana- Nitromifene 871 logues 533 Neomycin C 766 Nitromifene citrate 870, 871 INDEX 921

Nitrosoureas 801, 808 Nonglycoside inotropic agents Nucleic-acid amplification Nitrosulfathiazole 604 883 techniques 782 110, 122 Nonhypnotic sedative 841 Nucleotidase 817 Noninsulin-dependent diabetes Nylidrin hydrochloride 368 Nylidrin hydrochloride 368, 370 mellitus (NIDDM) 668 Nisentil (R) 549 Nonpeptide 339 O NK cell 832 Nonsedating second-generation O-amino benzaldehyde NMDA 219, 254, 268 antihistaminics 508 cyanohydrin 285 N-methyl-D-aspartate (NMDA) Nonselective α-antagonists 388 O-desmethylastemizole 507 receptor 124 Nonsteroidal antiandrogens 871 Object space 67 N-methyl-4-phenyl 1, 2, 3, 6 Nonsteroidal inotropic drugs 885 Obligate intracellular parasites tetrahydropyridine 549 Nonsystemic antacids 776 855 NMR-spectroscopy 66 Norastemizole 507 Observed solvation free-energy (∆∆G ) 99 Nonsegmented flatworms 653 Nontoxic 664 sol Non sulfonylureas 672, 678 Nonzwitterizonic species 508 Oestradiol benzoate 701 Non sulphonylurea oral Nor- 309, 310 Oestradiol enanthate 701 hypoglucemic agents 678 Noradrenaline 374, 375 Oestradiol undecanoate 701 Non-apeptide entity 268 Noradrenergic 848 Oestradiol 3, 48, 691, 698, 700, 701 Non-barbiturate sedatives 200 Noramidopyrine methane- Non-barbiturates 170, sulfonate sodium 290 Oestriol 691, 698, 699, 700 171, 190, 198, 199 Norepinephrine 304, Oestrogen activity 870 Non-cell cycle phase specific 339, 384, 398, 431 Oestrogen receptor 871 drugs 797 Norestemizole 507 Oestrogen triphenylethylene 870 Non-depolarizing muscle relax- 123 Oestrogens 691, 692, 698, 705, ants 227 Normal cells 798 870 Non-insulin-dependent diabetes Normeperidine 337 Oestrone 691, 698, 700, 701 mellitus (NIDDM) 675, Normorphine 308 Ofloxacin 785, 786, 787, 788 677, 678 Noroxymorphone 308 Oil-gas-partition coefficient 119 Non-mercurial diuretics 439, Oil of wintergreen 281 444 Noscapine 567, 574, 576, 579 Novel drugs 60 Oldest synthetic local anaesthetics Non-NMDA 254 153 Novel ligands 66, 82 Non-resistant 621 OP -Receptors 307 Novel medicinal compounds 2 1 Non-resistant falciparum malaria OP -Receptors 307 621 NPH iletin 670 2 OP -Receptors 307 Non-selective α-blocking drugs NPH insulin 670 3 Open-chain 218 388 NSAIDs 95, 97, 522, 523, 530, Open-chain ureide 187 Non-steroidal anti-inflammatory 533, 541, 813 drugs (NSAIDs) 95, 97, NSC 45388 827 analgesic 124, 305 522, 813 N-tert-butyl norepinephrine 54 Opiate receptors 275 Non-steroidal oestrogens 702, Nuclear androgen receptors 872 304, 306 703, 706 Nuclear overhauser effects Opioid ‘agonist’ 339 Nonclassical bio-isosteres 48, (NOEs) 71 Opioid alkaloids 307 49 Nucleic acid synthesis inhibitor Opioid analgesics 305 859 922 MEDICINAL CHEMISTRY

Opioid antagonists 309 Oxmetidine 517 Para-aminobenzoic acid esters Opioid peptides 306 Oxmetidine hydrochloride 26 Opioid receptor 307, 311 516, 517, 518 Para-aminosalicylic acid (PAS) Opioid receptor types 307 Oxolinic acid 785 783 Opioids 304, 306 Oxydihydroquinoline 362 Para-nitrosulfathiazole 604 Oppenauer oxidation 317, 708 Oxymetazoline 381 Para-sympathetic blocking drugs 409 Optimization of a lead 73 Oxymetazoline hydrochloride Parabanic acid 172 Optimization of lead compounds 375, 381, 385 98 333, 334 4, 5, 274, 275, 276, 278, 284, 297, Optimized conformation 55 Oxymorphone hydrochloride 312 298 Oral anticoagulants 882 Oxyphenbutazone 3, 5, 6, 292, 293, 300, 542 Paracetamol (acetaminophen) Oral contraceptives 882 274, 298 Oxypurinol 541 Orally active semisynthetic Paraldehyde 118, 124, 125, Oxytetracycline 3, 776 cephalosporin 756 191, 200 Oreintation map (OMAP) 87 P Paralysis agitans 546 Organ imaging 888 Parameterization 65 P-1534 818 Organic ligand 444 Parameterization of force fields P-388 818 Organomercurials 444 65 P-acetamido phenol 618 Orphan drug 829 Paramethadione 210, 211, 220 P-acetamidobenzene sulphonyl Orphan opioid receptor 307 Paranitrosulfathiazole 604, 606 chloride 586 557, 561 Paranitrosulphathiazole 604 P-aminobenzenesulphonamide Orphenadrine citrate 416, 424, 582 Parasympatholytic 409 556, 557, 560 P-aminobenzoic acid 134 95 Ortho-propoxy moiety 159 P-aminophenol analogues 275 Parent molecule 92 Orthocaine 133, 131 p-chlorophenyl guanidine 638 Parent tetracyclines 777 Orthoform 131 P-glycoprotein transporter 505 Parkinson syndrome 561 Osmotic diuretics 475 P-hydroxybenzyl-penicillin 738 Parkinsonism 546 Osmotic electrolytes 475 P-nitrophenol 277 Parkinsonism produced by MPTP Osmotic nonelectrolytes 475 548 PABA 166, 593, 604, 607, OTC-drugs 255 608 Parkinson’s disease Outward transport 799 546, 547, 548 Pacemakers 219 Oxacillin 746, 748 Partial cell-death 829 Paludrine 613 Oxacillin sodium 748 Partial salols 281 Pamaguin 623, 632 Oxamniquine 659, 660 PAS 879 Pamaquine 613, 623, 625, 626, Oxandrolone 695, 696, 697 631, 632 Pathway of biosynthesis of mycobactins 783 Oxazine ring 786 Pamaquine naphthoate 623 Pd-on-charcoal 658 Oxazolidine-2, 4-dione 209 Pamaquin’s stereochemistry 632 PEMA 221 Oxazolidinediones 209, 210, Pancreatic polypeptide 668 217, 218, 220 Pemoline 260, 261, 270 230, 247 Oxazolones 742 Pemoline conjugates 270 Papaverine 304, 424 Oxazolone structure 741 427, 428, 430 Para-aminobenzoic acid (PABA) Oximetidine hydrochloride 518 26, 593 INDEX 923

Penaldic acid 740 Peptide docking 79 Phenacetine 4, 5 Penicillamine 738, 739, 740, 741 Peptide ligand 79 Phenacaine base 153 Penicillin 42, 737, 738, 739, Peptidoglucolipids 783 P-gp substrate 362 740, 741, 742, 743, 752, Peptidoglycolipids 782 P-glycoprotein transporter 505 764, 766 Permethrin 663 Phenanthrene aminocarbinols 34 Penicillin G 166, 748, 749, PG 541 Phenanthroindolizidines 821, 756, 770 Peptone 721 824 Penicillin G-sensitive infections Peripheral α-adrenoceptor Phenanthroquinilizidines 821 747 stimulant 385 Phenanthroquinolizidines 823 Penicillin V benzathine 752 Peripheral actions 297 287, 288, 299, 542 Penicillin V hydrabamine 752 Peristaltic activity 652 Phencarbamide 417, 424 Penicillin variants 744 Peroxisome proliferator-activated 124 Penicillin N 754 receptor-r Phencylidine 836 Penicillin-V 744, 746, 752 (PPAR) 680 Pheneramines 501 Penicillinase 747 Peroxisome proliferator-activated Phenetermine 266 Penicillinase-resistant penicillins receptors 681 Phenindamine 510, 513 746, 751 Perphenazine 844, 845, 847 Phenindamine tartrate 510, 511, Penicillins related to ampicillin Petazocine 337 513 753 3, 4, 322, 323, 324 Pheniramine 515 Penicilloic acid 740, 741, 743, Pethidine hydrochloride 322, Phenobarbital 24, 173, 744, 746 323, 337 176, 177, 184, 198 199, Penillic acid 741, 743 Pfitzinger reaction 150 205, 206, 213, 216, 220, Penilloaldehyde 739, 740, 744 221, 222, 712 PG12 865 Penilloaldehyde-carboxylic acid PGF 865 Phenobarbitone 176 740 2 Pharmacodynamic 50 Phenoformin 681 Penilloic acid 740, 744 Pharmacokinetic 50, 91, 726 Phenol 44, 280 Penniloaldehyde 738 Pharmacophore 85, 88 Phenolic functional moieties 392 Pent-2-enylpenicillin 737 Pharmacophore models 85 Phenolic glycolipids 783 Pentaquine 628, 631, 632 Pharmacophore vs binding-site 326 Pentaquine phosphate 623, 628, models 85 Phenoperidine hydrochloride 630 Pharmacophoric hypothesis 85 322, 326, 339 320, 321, 337 Phase nonspecific drugs 796 420, 501, 504, Pentetrazol 260, 262 Phase specificity 796, 799 505, 553, 843, 839 54 Phase-specific drugs 796, 797 Phenothiazine analogue 554 Pentobarbital sodium 183, 199 Phenacaine 153 Phenothiazine antihistaminics Pentobarbitone sodium 183 501 Phenacaine hydrochloride 152, tartrate 428, 429, 153 Phenothiazine antipsychotics 501 431 Phenacemide 214, 215, Phenothiazine compounds 843, Pentolonium tartrate 428 218, 221 844 Pentoxyverine 574 274, 275, 276, Phenothiazine derivatives PEP calculations 100 277, 278, 298 486, 501, 514, 558 Peptide complexation 82 924 MEDICINAL CHEMISTRY

Phenobarbital sodium 184 Phthalylsulfathiazole 598, 599, Plasma-extenders 367 Phenothiazine nucleus 555 601, 602 Pirenzepine hydrochloride 423 Phenoxybenzamine 388 Phthalylsulphacetamide 600 540, 541, 542 Phenoxybenzamine hydrochloride Phthalylsulphathiozole 599 Pituitary-adrenocortical function 388, 389, 391 Phthalylsulphatiazole 599 731 Phenoxymethyl-penicillin 738, Physical theory 119 Pivampicillin hydrochloride 754 744, 752 Physostigmine 248, 399, 406, Plant products 819 Phenoxymethyl pinicillin calcium 408 Plasma esterases 159 752 Physostigmine salicylate 403, Plasma half-life 722, 723, 726, Phensuximide 211, 212, 221 406, 408 727, 730, 731, 732 Phentermine 264, 265, 266, 270 Phytosterols 690 Plasma-renin activity 355 388, 389 Picene 687 Platelets 655 Phentolamine hydrochloride Picrotoxine 254 Platyhelminthes 652 389, 391 Pilocarpine nitrate 399, 402, 403 Plicamycin 826 Phentolmine 389 Pimobendan 885, 886 Podophyllotoxin 824, 825 Phenyl salicylate 280, 281 Pindolol 395 Polar sulphamoyl- Phenylbutazone 3, 5, 6, 291, Pinworm 653 chlorobenzamide 467 293, 300, 542 Pipemidic acid 785 Polythiazide 445, 453, 455 Phenylbutazone 6 Piperacillin sodium 750 Polythiouracil 875 P-glycoprotein 362 Piperazine 654, 655 Poppy plant 304 Phenylephrine 846 Piperacillin 752 Pork tapeworm 653 Phenylethyl malonamide (PEMA) Piperazine antihistaminics 505 Positional isomers 54 221 Piperazine derivatives 498 Potassium acetate 475 Phenylpropanolamine 382, 385 Piperazines 653, 654 Potassium channel activators 889 Phenylpropanolamine hydrochlo- Piperiazine 661 Potassium depletion 720, 723 ride 375, 382 Piperidine analogues 549 Potassium guaiacosulphonate Phenylpropylamine analogues 572, 573 327 Piperidine antihistaminic 507 Potassium guiacosulfonate 572 Phenytoin 207, 208, 213, 216, Piperidine or tropane derivatives 712, 882 140 Potassium iodide 568, 570, 571 Phenytoin sodium 206, 207, Piperidinediones 200 Potassium secretion 720 208, 220 Piperidino 163 Potent mu (µ) opioid agonists Pholcodine 574, 578, 579 Pipobroman 826, 828, 829 307 Phopholipids 868 Pipradrol 840, 841 Potential biological activity 50 Phosphamide mustard 804 Pipradrol hydrochloride Potential-dependent calcium channels 350 Phosphate 654 840, 843 ‘Potential-drug candidate’ in Phosphodiesterase III 884 Pirbuterol 387, 388 silico 90 Photodynamic therapy (PDT) Pirbuterol hydrochloride PPA 385 894 386, 387 Practolol 396 Phosphodiesterase inhibitors 883 Pirenzepine 420, 423, 425 Pramocaine 153 Phthalylsulfacetamide 598, 600, Piperonyl butoxide 663 601, 602 PPARs 681 Pramoxine 155, 165 PPARr 680 Pramoxine hydrochloride 152, 153, 154 INDEX 925

Precursor protein 659 Procainamide hydrochloride 360 Propanediol carbamates 839 Prednisolone 522, 723, 726 Procaine 42, 131, 134, 140, Propanetheline bromide 415 Pramoxine base 154 147, 156, 157, 158, 166, Propanidid 116 p-Nitrophenol 277 443, 500 Propantheline 415, 712 PMZ 504 Procaine hydrochloride 131, Propantheline bromide 415, 416 133, 134, 144, 166 Prenylamine base 369 Proparacaine 157, 166 Procaine base 134 Pregnenolone 704, 708 Proparacaine hydrochloride 138, PMOC 306 Prednisone 723, 726, 167 802, 809, 822 Procaine, 158 Propiomelanocortin (PMOC) Pregnanediol 707 Procaine merethoxylline 443 306 Prenylamine 369, 371 Prochlorperazine 847 fumarate and Prenylamine lactate 369, 370 Procyclidine 553, 554 pentazocine 332 Prepared ipecacuanha Procyclidine hydrochloride Propoxycaine 140, 157, 159 568, 569, 571 417, 425, 553, 554 Propoxycaine hydrochloride 131, Preproinsulin 669 Prodrug 3, 583, 598, 648 140, 166, 167, 328, 339 Presence of thiazolidine ring 740 Production of microfilaria 663 Propoxyphene 18, 30, Prevention of histamine release A 306 Propoxyphene cyclic analogue 515 Proenkephalin B 306 Prilocaine 145, 155, 160, 164, 18 306 166 Propranolol 363, 394, 395, 396 Profenamine 554 Prilocaine base 145 Propranolol base 364 691, 707, 708, Prilocaine hydrochloride 144, Propranolol hydrochloride 363, 709, 870 145, 166 364, 394, 399 Primaquine 626, 627, 632 Progesterone metabolism 709 Propylthiouracil 874, 876 Primaquine base 627, 628 Proguanil 614, 637, 640 Prospective ligands 66, 81 Primaquine phosphate 623, 626, Proguanil base 639 Prostacyclin 867 627, 628, 631 Proguanil hydrochloride 637, Prostaglandin 865, 867 Primary amine metabolites 606 638, 639, 640 Prostaglandin (PG) 865, 719 Primary effects of Proinsulin 669 Prostaglandin (PG) synthesis 95, mineralocorticoids 720 Proinsulin folding 670 301, 541 Primary lateral sclerosis 91 Prolonging cardiac action 364 Prostaglandin analogues 867 Primidione 214 Promethazine 501, 502, 504 Prostaglandins and other Primidone 214, 221, 222 Promethazine hydrochloride eicosanoids 865 Principle of mixed moieties 10 499, 502, 504, 513 Prostanoic acid 865 Pro-opioid proteins 306 Promethazine teoclate 502 Protamine 670 Probable structure of penicillin Promethazine theoclate 502 Protamine sulphate 671 743 Promethazines 501 Protamine zinc 671 Probe atom 73 Prompt Insulin zinc suspension Protamine zinc insulin 671 Probenecid 538, 539, 541 671 Protamine zinc insulin injection Probucol 868, 869 Pronethalol 392, 393 671 Procainamide 360, 362, 363, Prontosil 582, 583 Protamine zinc insulin suspension 553 Pro-opiod proteins 306 671 Protein-anaesthetic interactions 926 MEDICINAL CHEMISTRY

121 Pyremethamine 644 Quantum chemical methods 65 Proton donating 607 Pyrethrins 663, 664 Quantum mechanical approach 7 Protein receptor hypotheses 121 Pyrethroids 663, 664 Quantum mechanical calculation Protonated resonance form of Pyrethrolone 663 65 tetracaine 159 Pyrethrum and pyrethroids 663, Quantum mechanical methods 63 Prothrombin 887 664 Quantum mechanics 7, 62, 63, Proton transport system 562 Pyrethrum extracts 663 65, 101 Prototype drug molecules 92 Pyribenzamine hydrochloride Quaternary ammonium Prototype of all corticoid 515 anticholinesterase 407 receptors 722 Pyridostigmine 406 Quaternary ammonium Prototype of all glucocorticoids Pyridostigmine bromide 403, cholinomimetics 403 722 406, 407, 408 Quaternization 246, 421 Proxymetacaine 138, 155 Pyridoxine 561 Quinacrine 613, 621 Proxymetacaine base 139 Pyrilamine 515, 560 Quinacrine hydrochloride 633, 636 Proxymetacaine hydrochloride Pyrilamine maleate 491, 492, 131, 138, 139 493, 560 Quinalbarbitone 185, 186 Quinalbarbitone sodium 184, Proxyphylline 259 Pyrimethamine 637, 640, 641, 186, 199 Pt complex 829 642, 643, 644, 645, 646 Pseudoephedrine 52, 53 -derived nonthiazide Purkinje fibre cell 357 diuretic 465 Pyrethric acid 663 Pyrethric acid 663 Quinazolone 200 Proxyphylline 256 Pyrethrin I 663 Quinethazone 462, 463, 466 Pseudo tropane 129, 130 Quinidine 362, 613, 614 Pseudo-oligosaccharides 789 Pyrethrin II 663 Quinidine gluconate 362 Psychoses 836 Pyrimidine 594 Quinidine sulfate 358 Pt-containing drug 800 Pyrimidine analogues 640, 815 Quinidine sulphate 358, 362 Pteridine moiety 637 Pyrimidine diuretics 474 15, 613, 614, 621, Pteroic acid 607 Pyrimidine nucleoside 622, 646 Purine 473 antimetabolite 817 Quinine acetylsalicylate 15 Purine biosynthesis 817 Pyrogenic factors 296 Quinine analogues 646 Purine diuertics 473, 474 Pyrrocaine 147, 156 Quinine bisulfate 646 Purine or xanthine diuretics 473 Pyrrocaine base 148 Quinine sulphate 646 Purines 811 Quinine-clindamycin 646 Purple foxglove 710 Pyrrocaine hydrochloride 144, 147, 148 Quinine-pyrimethamine- Putative active metabolite 221 sulfadiazine 646 Pyrrolidine ring 678 pamoate 659, 661 Quinine-tetracycline 646 Pyrrolidino 163 Pyrazinamide 784, 785, 788, Quinisocaine 151 877 Q Quinocide 631, 632 Pyrazine ring 678 Quinocide hydrochloride 623, QSAR studies 36 Pyrazolodiones 287, 542 631 Quantitative structure-activity 287, 542 Quinoline and iso-quinoline relationships (QSAR) 6, Pyrazolones and pyrazolodiones analogues 149 542 23, 32, 33, 36, 90 INDEX 927

Quinoline derivatives 285 Recognition site points 85 843 Quinoline nucleus 632 Recombinant 832 Ribavirin 857, 859, 860 Quinone 547, 548 Reduced mineral corticoid Ribonucleic acid (RNA) 854 Quinone-imine system 622 activity 570 Rifabutin 784 Quisqualic acid 268 Reduction in interior negativity Rifampicin 764, 877, 880 219 Rifampicin-a 880 R Refampicin 880 Rifampin 645, 784, 880, 882 R – (–) naproxen sodium 52 Regression methods 99 Rifobutin 788 R(–) isomer epinephrine 55 Regular insulin injection 671 Rigid opioids 310 (R)-amphitamine 270 Relaxation of the skeletal muscle Rigid-site points 86 246 (R) and (S) isomers of ampheta- Ro 31-8959 82, 83, 84 REM 268 mine 270 Robotics 93 Renin-angiotensin pathway 349 Rapid influx 357 95 Repaglinide 679 Radiation incidence 796 Rosiglitazone 680 Repetitive action 664 Radiation therapy 799 Roundworm 652 Radioimmunotherapy 888 Replication and transformation Recombinant 332 855 S 558, 560, 561, Radioisotopes 887, 888 S-DNA : replication phase 797 837, 838, 839 Radiolabeled benzodiazepines S(+) isomer epinephrine 55 195 Reserpine and related alkaloids 837 S-DNA : replication phase 798 Radionucleotides 888 Resonance 31, 33 S-oxidation 518 Radiopharmaceuticals 888 Resonance effect (R) 29, 28, S-phase specific 817 Radiosensitizer 865, 887 30, 32, 158 Salazosulfapyridine 598, 601, Ranitidine 516, 517, 518 Replication phase 798 602 Ranitidine N-oxide 518 RFLP 782 Salbutamol 386, 387 Ranitidine S-oxide 518 Resonance stabilised 607 (S)-isomer of amphetamine 270 Rapid-acting insulin 671 Resonance structures of aniline SA node 356 Rate of distribution 41 31 RIF 784 Rational approach to drug design Resonance forms of unionized Salem and Aviado’s hypothesis 6 tetracaine 159 567 Rational designing 93 RNA 854 279 Rauwolfia alkaloids 375 RIMAs 843 283, 299, 542 Receptor 27, 46, 50, 161 Resonance form 159 Salicylate 299 Receptor selectivity 312 Resperpine 839 Salicylic acid 298, 279, 281, Receptor site 16, 84, 155, 706 Resting organisms 880 280 Receptor site cavity 73 Restriction fragment length Salicylic acid analogues Receptor-binding site 86 polymorphism 279, 542 Receptor-ligand complexes 60 (RFLP) 782 Saline expectorant 570, 568 Receptor-ligand recognition 79 Reverse designing 93 Salivary glands 720 Receptor-volume of interest 76 Reverse transcriptase 69, 892 Salmetrol xinafoate 386, 387 Reciprocating shaker 721 Reversible inhibitors (RIMAs) Salol 280, 281, 542 Salol principle 14, 281 928 MEDICINAL CHEMISTRY

Salsalate 282, 299, 542 SAR of oxacillin 748 cephalosporins 758, 760 Saluretic activity 470 SAR of oxamniquine 660 Second generation tetracyclines Santoquin 620, 621 SAR of oximetidine 518 777 Sapogenins 690, 713 SAR of pamaquine 632 Second line fluoroquinlones 788 Saponins 686, 713 SAR of pentaquine 632 Second phase of ionization 197 SAR : terfenadine 505 SAR of perphenazine 847 Second-generation non-sedating SAR of acetohexamide 673 SAR of phenindamine 513 antihistamines 486, 505 SAR of acrivastine 509 SAR of primaquine 632 Second-generation sulfonylureas 676 SAR of amino-alcohol esters 424 SAR of probenecid 541 Second-line drugs 785, 790 SAR of aminoalcohol carbar- SAR of pyrilamine 494 Second-line tuberculostatic drug mates 425 SAR of streptomycin 765 788 SAR of ampicillin 749 SAR of sulfadiazine 594 Sedative and hypnotic 170, 177, SAR of antazoline 500 SAR of sulfamethazine 595 205 SAR of artemisinin 647 SAR of sulfapyridine 594 Sedative and hypnotic drug 170 SAR of astemizole 507 SAR of sulphanilamide 593 Sedative Expectorants 568 SAR of benztropine 560 SAR of ticarcillin 751 Sedatives 170 SAR of buclizine 501 SAR of triprolidine 514 Segmented flatworms 653 SAR of bumetanide 470 SAR of 494 Selective and specific reaction SAR of carbetapentane 579 SAR to 494 829 SAR of cefamandole 758 SAR-delta receptor agonists 311 Selective delta receptor ligands SAR of ceftibuten 762 SAR-kappa receptor agonists 310 SAR of cefuroxime 760 310 Selective H2-antagonist 518 SAR of cephradine 757 SAR-Mu antagonists 308 Semi-Lente iletin 671 SAR of chlorcyclizine 500 SAR-of aminoamides 425 β Selcetive 1 blockers 396 SAR of chloroquine 621 Saralasin 349 Seemann’s hypothesis 567 SAR of chlorpheniramine 514 SARs of aryloylphenoxyacetic S-DNA 798 SAR of chlorthalidone 466 acids 470 Semiquinone 547, 548 SAR of diphenhydramine 490 SARs of tetracyclines 777 Semitard 671 SAR of ethionamide 881 SARs of diuretics 455 Seretonergic 848 SAR of ethopromazine 555 Satoh and minami’s method 312 Serotonin 300, 304, 339, 839 SAR of glimepiride 678 Schistosomiasis 653 Serotonin-regulated thermal SAR of glyburide 677 Sclerosing agent 636 controlling centre 300 SAR of HCQ 622 Scoring 101 Sex hormones 686, 690, 691 SAR of indapamide 467 Searching for similarity 88 Sex incidence 795 SAR of kanamycin 767 Secobarbital sodium 184, 199 Shape of the steroid 689 SAR of levopropoxyphene 579 Second generation 397 Short-acting barbiturate 54, 182, SAR of meclizine 501 Second generation antihistamines 196 SAR of methapyrilene 496 505 Short-acting sulphonamide 597 β SAR of methicillin 748 Second generation -blockers Short-range emitters 888 396 SAR of neomycin 766 Short-to medium acting Second generation SAR of orphenadrine 560 glucocorticoids 720 INDEX 929

Shorter-acting lidocaine 145 Somatostatin 668 Steroidal antiandrogens 872 Silver sulfadiazine 604, 605 Some alkaloids 686 Steroidal compounds 687 Silver sulphadiazine 605 Sontoquine 623 Steroidal drugs 687 Simple comparisons 88 Sophisticated automated method- Steroidal oestrogens 698, 705 Simulations 82 ologies 77 Steroidal saponins 713 Simulations and the thermody- Sophistieated laboratory diagnos- Steroids 522, 686, 687, 689 namic cycle 82 tic methods 782 Sterols 690 Sino-atrial (SA) node 356 Soterenol 49 Streptomycin sulphate 764, 879 Site of action 71 Sparfloxacin 788 Stigmasterol 690, 691 Sitosterols 690 Spasticity 246 Stilbesterol 691, 702 Skeletal muscle relaxants 226 Spatial arrangements 16 Stimulant (irritant) expectorants Skelly solve B petroleum ether Specific electronic structure 63 571 722 Specific immunosuppressed Streptamine 789 Sodium 752, 753 patients 790 Streptomycin 15, 764, 784, 790, Sodium acid phosphate 475, 476 Specific pharmacophore 86 877, 879 Sodium aurothiomalate 537, 538 Specific transformation 67 Streptomycin Sulphate 764, 879, Sodium aurothiomalate 535 Spectinamine 789 882 Sodium barbiturates 197 Spinal anaesthesia 129 Streptoniazid 15 Sodium channels 155, 161 Spiric acid 279 Strophanthidine 882, 883 Sodium chloride aerosols 566 Spironolactone 471, 472, 873 Structural analogues 85 Sodium cromoglycate 515, 516 SPLICE 76 Structural isomer of proparacaine Sodium glycocholate 713 Spring constant 61 166 Sodium nitroprusside 353, 355, Standard orientation 90 Structurally non-specific drugs 350 Stanozolol 696 24 Slow influx 357 Stanzolol 697 Structurally specific drugs 23 Shortened ST-interval 357 Stercuronium iodide 227, 233 Structure-activity relationship 16, 23, 38, 155, 345, 385, Sodium dibunate 567 S-phase specific 817 394, 718, 771, 775, 776 S-oxidation 518 Stereo-selective (trans) synthesis Structure of chloramphenicol 317 Sodium reabsorption 720 767 Stereochemical changes 18 Sodium retention 720, 723 Structure of the penicillins 738 Stereochemical effects 120 Sodium salicylate 282, 299, Structure-based drug design 542 Stereochemistry 50, 54, 689 66, 67, 68 Sodium salt of benzyl penicillin Stereoisomers 50 Structure-baided drug design 66 742 Stereospecific aspects 664 Strychnine 254 Sodium sulfadiazine 607 Steric factor 27, 31, 32 Substituted alkanediols and Sodium taurocholate 713 Sterimol 32 analogues 238 Sodium thiamylal 115 Steroid backbone 686 Substituted phenyltetra- Sodium valproate 215 Steroid hormone 691 zolylalkanoic acid 39 Solapalmitenine 821, 823 Steroid therapy 537 Substrate 71 Solapalmitine 821, 823 Steroid-receptor complex 722 Success rate 90 Solid-state conformation 496 Steroidal alcohols 690 Succinic dehydrogenase 636 Soluble nitro reductases 606 Succinimide analog 213 930 MEDICINAL CHEMISTRY

Succinimide system 221 602 Sulphinpyrazone 293 Succinimides 205, 210, 217, Sulfasalazine 601, 602 Sulphonamide moiety 457, 593 218 Sulfathiazole 584, 587, 589, Sulphonamide related compounds Succinylcholine chloride 233, 594, 598, 599 604 247 Sulfhydryl enzymes 444 Sulphonamide structural ana- Succinylsulfathiazole 598, 600 Sulfinpurazone 538 logues 457 Succinylsulphathiazole 599, 600, Sulfinpyrazone 293, 300, 542 Sulphonamide-trimethoprim 602 Sulfisoxazole 595, 596, 597, combinations 583 Sucrose 682 598, 607 Sulphonamides 456, 457, 583, Sufacytine 598 Sulfisoxazole acetyl 595, 597, 584, 593, 595, 598, Sufalene 584 598 603, 604, 608, 609, 646 Sufanilamide 585, 586 Sulfogaiacol 571, 572 Sulphonamides for general 331, 340 Sulfones 644 infections 584 Sufetanil 307 Sulfonylurea hypoglycemic Sulphonamides for intestinal infections 598 Suitably-sized spacer fragments agents 672 80 Sulfonylureas 672, 673 Sulphonamides for urinary infections 595 Sulbactam 751 847 Sulphonylureas 678, 681 Sulbactam-ampicillin 752 523, 525, 527 Sulphoxides 504 Sulfacetamide 595, 598, 601, Sulmazole 885, 886 Sulthiame 215 603 Sulpha drugs 582 Sultiame 214, 215, 221 Sulfacetamide sodium 603, 604 Sulphabenzamide 598 Suppressor T-cells 799 Sulfacitine 595, 597 Sulphacetamide 595 Surface anaesthetic 152 Sulfacytine 597 Sulphacetamide sodium 603 Surface or topical anaesthesia Sulfadiazine 584, 586, 587, Sulphadiazine 587, 595, 598 128 594, 595 Sulphadimidine 590 Surgical anaesthesia 122 Sulfadimidine 584, 588, 590, Sulphafurazole 596, 598 591 231, Sulphafurazole 598 Sulfadoxine 642, 644, 646 233, 234, 247 Sulphaguanidine 598, 602 Sulfafurazole 595, 596 Suxamethonium-induced muscu- Sulphanilamide 582, 583, 593, lar fasciculations 231 Sulfaguanidine 598, 599, 600 594, 607, 608, 645 Suxethonium bromide 233, 234 Sulfamethoxazole 645 Sulphanilamide-type antibacterial Suxethonium chloride 234 Sulfalene 591, 592, 595 action 608 Sweat glands 720 Sulfamerazine 584, 589, 590, Sulphanilamide-type compounds Sweet wormwood 646 595 604 Sympathomimetic drugs Sulfamethazine 590, 595 Sulphanilic acid 585 375, 384 Sulfamethiazole 595 Sulphapyridine 583, 586 Sympathomimetics 344 Sulfamethizole 584, 592 Sulphasalazine 601, 712 Synaptic inhibition and excitation Sulfamethoxazole 645 Sulphate-conjugates 298 219 Sulfametopyrazine 591, 643 Sulphated glucosamine 886 Synchronizing antineoplastic Sulfanilamide Sulphathiazole 587 drug 798 584, 589, 590, 592, 596, 606 Sulphhydryl component 86 Synchronizing drug 798 Sulfapyridine 584, 586, 594, Sulphide metabolite 527 Synthesis of chloramphenicol INDEX 931

769 Tea 566 Theophylline derivative 259 Synthesis of tropic acid 410 Technetium-99 443 Therapeutic radioisotopes 887 Synthesized local anaesthetics Technetium-99m 443, 889 Therapeutic target 60, 66, 71, 81 162 Terbutaline 54, 386, 387 Thermal shock proteins 720 Synthetic antimalarial drug 621 Terfenadine 505, 506, 508, 509 Thermocortical and limbic Synthetic newer target drug Terpin hydrate 571, 572, 573 systems 124 molecules 32 tert-butyl norepinephrine 54 Thermodynamic activity 24 Synthetic oral hypoglycemic Tert-butyl-α-phthalimido- Thermodynamic cycle 82 agents 672 malonaldehydate 746 Thermodynamic cycle-perturba- Synthetic steroids 718 Tertiary amines 819, 821 tion approach 99, 100 Synthetic target(s) 81 Tertiary-butyl functional moieties Thiabendazole 655, 658, 659 Syrup of acacia 568 397 Thiamazole 875 Systemic antibacterial drugs 584 Testolactone 830, 831 Thiamylal 124 T TEM 807 Thiamylal sodium 115, 124 THFA 593 Thiazide diuretics 445, 454, 455 Taft constants 57 Testosterone 691, 692, 693, 696, 443, 444, 445, 462, Taft’s steric factor 28, 32, 33 694, 697, 870 467 Target identification scheme 94 Testosterone propionate 3 Thiazolidine ring 740 Tailor-made compound 2 Tetracaine 155, 156, 157, 158, Thiazolidine-β-lactams 742 Tailoring 18 159, 164 Thiazolidines 742 Talampicillin napsylate 754 Tetracaine hydrochloride 131, Thiazolindiones 672, 680 Tamoxifen citrate 870, 871 135 Thioguanine 814, 816 Tamoxifene 870 Tetracycline 44, 712, 772, 774, Thioisonicotinamide series 881 775, 776, 777 Tapeworms 653 Thiopental 124, 189 Tetrahydrofolic acid 593 Target enzyme 800 Thiopental sodium 111, 123, Target proteins 61 Tetrahydroisoquinoline residue 187, 188, 189, 197, 199 227 Target structure 393 Thiopentone sodium 111, 170 Thalicapine 821, 822, 823 Target tissue 871 Thiophene analogs 514 Thalidasine 821, 822, 823 Target-cells 798 Thiophene derivatives 485, 494 The topliss scheme 36 Target-drug-molecules 14, 22, Thioridazine 844, 845 304 77 Tthioridazine 847 500 Target-receptor interface 76 Thioridazine hydrochloride 847 Thenalidine tartrate 500, 501 Targets for antineoplastic agents Thiotepa 808 496, 515 795 Third generation cephalosporins Targetted drug molecule 50, 393 Thenyldiamine hydrochloride 760 496, 497 Tartar emetic 568 Third generation β-blockers 397 Thenylene hydrochloride 515 Tartrate 654 Third-generation cephalosporins Tautomerism 641, 876 Theobromine 256, 257, 258, 760, 763, 790 473, 474 Tazobactam 751 Thonzylamine hydrochloride Theofibrate 868, 869 Tazobactam-piperacillin 752 493, 494 Theophylline 256, 257, 269, TCP approach 99 Three-compartment kinetics 822 473, 474, 475, 882 TCP method 99 Thrombin 887 932 MEDICINAL CHEMISTRY

Thiobarbituric acid 173 Tracer techniques 22 Trimetaphan 430 Threadworm 653 330 429 Thymidylic acid 816 Tramadol hydrochloride Trimetaphan camsylate 427, 429 Ticarcillin 751 330, 339 Trimethadione 209, 211, 220 Thymidine kinase 859 Tretamine 808 Trimethaphan camsylate Thymidine triphosphate 892 Trans-stilbesterol 703 429, 431 Thymidines 811 Trans-tripolidine 53 Tropane derivatives 140 Thymidylate 812 Tranquilizer 836, 840, 844 Trimethoprim 595, 642, 643, 644, 645 Thymidylate kinase 892 Trans-diethylstilbesterol 3, 9, 10, 43, 48, 49, 702 Trimethoprim with Thymol 25, 24 Transcortin 731 sulphamethoxazole 643 Thyroxine 84, 870 Transcription of nucleic acids Trimethoprim-sulfamethoxazole Ticarcillin disodium 750 797 645 Tilidate hydrochloride 330 Transdermal patch 124 Trioxane 647 330 Transformation 67 Tripelennamine 492, 494, 496 Tilidine hydrochloride 330 Transition-state inhibitor of HIV Tripelennamine hydrochloride Timolol 395 protease 82 492, 493, 494 TIPP 311 Transport system 800 Tripolidine 53, 509, 511, 514, Ψ TIPP- 311 Transthyretin 84 515 Toad poisons 686 Treatment regimen 785 Triprolidine hydrochloride 511, 514 Tocainide 361 Trematodes 653 Trivabirin 859 Tocainide 360 Triamcinoline 522 Trofosfamide 803 Tocainide hydrochloride 363 Triamcinolone 727 Troglitazone 680, 681 Tolazamide 673, 674 Triamterene 478, 479, 480 Trometamol 476, 477 Tolazoline 388, 391 Tribromoethanol 117 Tromethamine 476, 477 Tolazoline (base) 390 Tribromoethyl alcohol 117 Tropeines 409 Tolazoline hydrochloride Trichinella spiralis 653 390, 391 Tropic acid 410, 419 Trichlormethiazide Tolbutamide 673, 674, 675, 445, 452, 455 Tropicamide 417, 419, 425, 676, 882 553 Trichloroethylene 110, 122 525 Tropicamide acetate 419 Trichostrongylus 661 Tolmetin sodium 522, 525, 526, Tropocaine 129, 130 Tricyclic antidepressants 553 527 Troxidone 209 Triethylene melamine (TEM) Tolubalsam 568 807 True cure 799 Topical anaesthesia 128 Triethylenemelamine 808 Trypsin 566 Transmembrane resting potential Triethylenethio phosphoramide Tuberculocidal 880 357 807, 808 Tuberculostatic drugs 880 Topical local anaesthesia 164 Triglycerides 868 Tubocurarine 227, 228, 247 Topliss scheme 36, 37, 38, 39, Trihexyphenidyl 551 227, 230, 40 Trihexyphenidyl hydrochloride 247 Topoisomerase 819 417, 425, 549, 551, 552, Tubulin 659 Topoisomerase inhibitors 800 553 Tumour biology 794 Torsion angle 61 Trihydrate 753 Tumour regression 829 Torsional relation 61 Trimeprazine tartrate 503, 504 Tumour selectivity and response INDEX 933

797 Valeramide-OM 24, 25 Vitamin D 686 Tropine 411 Valerate 701 W Tumour-associated compounds Valproate sodium 215, 216, 221 887 Valproic acid 214, 215 Wave mechanics 7

TXA2 865 Values 720 Weight gain 720 238, 240, 241, 249, Van der Waal’s constants 25 Whipworm 653 839 Van der Waal’s forces 163 Wilgerodt-kindler reaction 533 Tylocrebrine 821, 824 Van der Waal’s interactions 425 Wonder drugs 864 Tylophorine 821, 824 Vancomycin-peptide complex World health organization Tylophorinine 821, 824 81, 82 (WHO) 348, 612 Tyloxapol 566 Vanillin 559 Wuchereria bancrofti 653 Type 1 diabetes 668 Variant CoMFA 88 Wurtz-Fittig reaction 703 Type 2 diabetes 668, 678 Variants of insulin products 670 X Type 2 diabetes mellitus Vasopressor drugs 367 676, 681, 682 Vasodilators 367 X-irradiation 829 Types of isomeric drugs 54 Verapamil 366, 882 X-ray crystallography 66 Types of worm parasites 652 Verapamil hydrochloride 366 X-ray diffraction analysis 743 Xamoterol 398 U Verloop steric parameter 28, 32, 33 Xamoterol 398 Ulman condensation 295 Vermicides 652 Xanthine 473 Ultra-Lente iletin 671 Vermifuges 652 Xanthine derivatives 256 Ultra-short-acting barbiturates Vibrational spectra 65 Xanthine oxidase 541 187 Vidarabine 857, 858, 860 Xylometazoline 383, 385 Ultralente insulin 671 Xylometazoline hydrochloride Viewer space 67 Ultratard 671 375, 383 Unbonded class 61 Vinblastine 821, 822, 827 Xanthine diuretics 473 Undecanoate 701 Vincristine 802, 821, 822 Unidentified metabolite 831 Vincristine sulfate 822 Z UNITY-3DB 75 Vindoline 821 Z stereochemistry 762 Unknown receptor sites 84, 85 Vinyl ether 108, 121 Zidovudine 891, 892 Upper respiratory tract infections Viral Replication 855 Zinc chloride 671 775 Viral uncoating 561 Zinc insulin 671 Uracil 47, 815 Zinc-insulin crystals 670 Virus incidence 796 Urate crystals 820 Zn-S complexes 86 Virus-encoded enzyme thymidine Urea 475, 476 kinase 859 Zolamine 493 Uricosuric agent 5, 293, 538 Zolamine hydrochloride Visualization of molecular Uriedo-type moiety 218 493, 494 properties 88 Urinary tract infections 776 526 Visually assisted design 73 URTs 775 Zomepirac sodium 523, 526, 527 Voltage-activated sodium channel UTIs 776 Zoosterols 690 161 242, 243 V Volume expansion 720 Zwitterionic characteristic 95 Volume of distribution features 762 722, 726, 727, 731, 806 (Z)-isomer 514