《The Sulfonamides and Allied Compounds》

Chapter Ⅰ．History of Bacterial Chemotherapy1

(Ⅰ)DYES1

(Ⅱ)SEARCH FOR AN AGENT ACTIVE in Vivo1

(Ⅲ)PRONTOSIL2

(Ⅳ)SULFANILAMIDE3

(Ⅴ)SULFAPYRIDINE4

(Ⅵ)MODERN SULFA DRUGS4

(Ⅶ)THEORIES5

(Ⅷ)FUTURE DEVELOPMENTS IN CHEMOTHERAPY5

Chapter Ⅱ．Nomenclature，Classification and Synthesis of Sulfanilamide Derivatives7

(Ⅰ)NOMENCLATURE7

(A)SULFANILAMIDE DERIVATIVES7

(B)SULFONES，SULFOXIDES，SULFIDES AND DISULFIDES9

(Ⅱ)SYSTEM OF CLASSIFICATION10

(A)GENERAL CONSIDERATIONS10

(B)CLASSIFICATION OF SULFANILAMIDE DERIVATIVES10

(C)CLASSIFICATION OF COMPOUNDS RELATED TO SULFANILAMIDE11

(D)CLASSIFICATION OF SULFONES，SULFOXIDES，SULFIDES，DISULFIDES，ETC11

(Ⅲ)SYNTHESIS OF SULFANILAMIDE DERIVATIVES AND SULFONES11

(A)INTERMEDIATES11

(B)MANUFACTURE OF SULFANILAMIDE12

(C)MANUFACTURE OF SULFAPYRIDINE13

(D)MANUFACTURE OF SULFATHIAZOLE AND DERIVATIVES15

(E)MANUFACTURE OF SULFAGUANIDINE16

(F)MANUFACTURE OF SULFADIAZINE17

(G)MANUFACTURE OF SULFAMERAZINE(2-SULFANILAMIDO-4-METHYLPYRIMIDINE)18

(H)MANUFACTURE OF＂SULFAMETHAZINE＂(2-SULFANILAMIDO-4，6-DIMETHYLPYRIMIDINE)19

(I)MANUFACTURE OF BIS(4-AMINOPHENYL)SULFONE AND DERIVATIVES19

Chapter Ⅲ．Structure and Activities of Simple Sulfanilamide Derivatives21

(Ⅰ)SALTS OF SULFANILAMIDE(1-3：51)21

(Ⅱ)NUCLEAR-SUBSTITUTED SULFANILAMIDES(4，5：52)21

(Ⅲ)N1-SUBSTITUTED SULFANILAMIDES21

(A)N1-Acyclicsulfanilamides21

(B)N1-Isocyclicsulfanilamides23

(C)N1-Heterocyclicsulfanilamides25

(D)N1-Acylsulfanilamides37

(E)N1-Inorganic Derivatives of Sulfanilamide42

(Ⅳ)N4-SUBSTITUTED SULFANILAMIDES43

(A)N4-Ayclicsulfanilamides(53：108)43

(B)N4-Isocyclicsulfanilamides(54：109)45

(C)N4-Heterocyclicsulfanilamides(55-58：110-117)45

(D)N4-Anils of Sulfanilamide45

(E)N4-Sugar Derivatives of Sulfanilamide46

(F)N4-Acylsulfanilamides(65-68：123-129)47

(G)N4-Inorganic Derivatives of Sulfanilamide48

Chapter Ⅳ．Structure and Activities of Complex Sulfanilamide Derivatives149

(Ⅰ)NUCLEAR-N1-SUBSTITUTED SULFANILAMIDES149

(Ⅱ)NUCLEAR-N4-SUBSTITUTED SULFANILAMIDES149

(Ⅲ)N1，N4-SUBSTITUTED SULFANILAMIDES149

(A)N4-Acyclic-N1-substituted Sulfanilamides(92：162)149

(B)N4-Isocyclic-N1-substituted Sulfanilamides(93：165)149

(C)N4-Heterocyclic-N1-substituted Sulfanilamides(94，95：166，167)150

(D)N4-Anils of N1-substituted Sulfanilamides(96：168)150

(E)N4-Sugar Derivatives of N1-substituted Sulfanilamides(97，98：170，171)150

(F)N4-Acyl-N1-substituted Sulfanilamides150

(G)N4-Inorganic Derivatives of N1-Substituted Sulfanilamides154

(Ⅳ)NUCLEAR-N1，N4-SUBSTITUTED SULFANILAMIDES(145：246)155

(Ⅴ)UNCLASSIFIED DERIVATIVES OF SULFANILAMIDE(146：248)155

Chapter Ⅴ．Structure and Activities of Compounds Related to Sulfanilamide250

(Ⅰ)4-NITROBENZENESULFONAMIDES250

(Ⅱ)DERIVATIVES OF ORTHANILAMIDE AND METANILAMIDE251

(Ⅲ)ACYCLIC COMPOUNDS(170-173：280-281)252

(Ⅳ)ISOCYCLIC COMPOUNDS252

(A)Isocyclicsulfonamides252

(B)Derivatives of 4-Aminobenzoic Acid254

(C)Derivatives of 4-Nitrobenzoic Acid256

(D)Derivatives of Sulfanilic Acid(190：304)257

(E)Ketones257

(F)Quinones(193：307)258

(G)Isocyclicsulfenamides258

(H)Derivatives of Isocyclicsulfinic Acids258

(I)Isocyclic Selenium Compounds(198：311)258

(J)Miscellaneous Isocyclicamines(199：311)259

(K)Miscellaneous Azo Compounds(200：317)259

(L)Miscellaneous Isocyclic Compounds(201：318)259

(Ⅴ)HETEROCYCLIC COMPOUNDS259

(A)Heterocyclicsulfonamides259

(B)Miscellaneous Heterocyclic Compounds(217：335)261

Chapter Ⅵ．Structure and Activities of Sulfones340

(Ⅰ)ACYCLIC ISOCYCLIC SULFONES340

(A)4-Aminophenyl Acyclic Sulfones340

(B)Miscellaneous Acyclic Isocyclic Sulfones(222：350)340

(Ⅱ)BIS(ISOCYCLIC)SULFONES341

(A)Symmetrically Substituted Bis(4-aminophenyl)Sulfones341

(B)Unsymmetrical Bis(4-aminophenyl)Sulfones with One 4-Aminophenyl Group Substituted341

(C)Unsymmetrical Bis(4-aminophenyl)Sulfones with Both Nitrogens Substituted344

(D)4-Aminophenyl Isocyclic Sulfones345

(E)Miscellaneous Symmetrical Bis(isocyclic)Sulfones(248：369)345

(F)Miscellaneous Unsymmetrical Bis(isocyclic)Sulfones(249：369)346

(Ⅲ)ISOCYCLIC HETEROCYCLIC SULFONES346

(A)Sulfanilyl Heterocycles346

(B)Miscellaneous Isocyclic Heterocyclic Sulfones(252：374)347

(Ⅳ)BIS(HETEROCYCLIC)SULFONES347

(Ⅴ)HETEROCYCLIC SULFONES WITH THE S-ATOM A MEMBER OF THE HETEROCYCLIC SYSTEM(255：376)347

Chapter Ⅶ．Structure and Activities of Compounds Related to the Sulfones377

(Ⅰ)SULFIDES377

(Ⅱ)SULFOXIDES377

(Ⅲ)DISULFIDES377

(Ⅳ)MISCELLANEOUS DISULFOXIDES(270：387)378

(Ⅴ)MISCELLANEOUS DISULFONES(271：387)378

(Ⅵ)COMPOUNDS RELATED TO BIS(4-AMINOPHENYL)SULFONE378

(A)Selenium and Tellurium Compounds(272：387)378

(B)Phosphorus Compounds(273：388)379

(C)Arsenic Compounds(274：388)379

Chapter Ⅷ．Experimental Evaluation of Chemotherapeutic Activity389

(Ⅰ)ANTIBACTERIAL ACTIVITY TESTS389

(A)In Vitro Tests390

(B)In Vivo Tests396

(C)Relation of in Vitro to in Vivo Activity402

(Ⅱ)EXPERIMENTAL EVALUATION OF CHEMOTHERAPEUTIC ACTIVITY PREPARATORY TO CLINICAL TRIAL402

(Ⅲ)TABULATED SUMMARY：EXPERIMENTAL EVALUATION OF CHEMOTHERAPEUTIC ACTIVITY403

(A)Experimental Activities of Sulfa Drugs and Sulfones403

(B)References to Experimental Studies with Sulfonamides(298：412-6)404

(C)Illustrative Data404

Chapter Ⅸ．Relationship of Structure to Chemotherapeutic Activity422

(Ⅰ)SUMMARY OF RELATIONSHIPS OF STRUCTURE TO CHEMOTHERAPEUTIC ACTIVITY422

(A)Sulfanilamide Derivatives422

(B)Compounds Related to Sulfanilamide425

(C)Sulfones425

(D)Compounds Related to the Sulfones426

(Ⅱ)DISCUSSION OF VARIOUS CORRELATIONS BETWEEN STRUCTURE AND ACTIVITY426

(Ⅲ)GENERAL CONCLUSIONS427

(A)Classification of Drugs Having Sulfanilamide-Type Activity427

(B)Discussion of Exceptions to Generalizations42

(C)Requirements for Sulfanilamide-Type Activity438

(D)Development of New Drugs430

Chapter Ⅹ．Pharmacology of Sulfonamide and Sulfone Drugs434

(Ⅰ)GENERAL CONSIDERATIONS434

(Ⅱ)METHOD OF ASSAY IN BODY FLUIDS436

(Ⅲ)DEVELOPMENT OF A NEW CHEMOTHERAPEUTIC DRUG438

(A)Development Preparatory to Clinical Trial438

(B)Studies Preparatory to General Clinical Use441

Chapter Ⅺ．Theories of the Mechanism of Action of Sulfonamide Drugs466

(Ⅰ)FACTS FUNDAMENTAL TO A THEORY OF ACTION466

(A)Summary of the More Important Experimental Findings466

(B)Sulfonamide Antagonists467

(C)Sulfonamide Potentiators or Synergists473

(D)Action of Sulfonamides on Bacterial Toxins473

(E)Specificity of Action of Sulfanilamide Derivatives473

(F)Drug Resistance476

(G)Bacterial Population vs Concentration of Sulfa Drug Required for Bacteriostasis479

(H)Effects of Sulfonamide Drugs on Enzymes480

(Ⅱ)ESSENTIAL METABOLITE THEORIES482

(A)Theory of Woods and Fildes482

(B)Applications and Extensions of the Woods-Fildes Theory484

(C)Theory of Kohn and Harris493

(D)Theories Involving Ionization of Sulfonamides494

(Ⅲ)MISCELLANEOUS THEORIES506

(A)Peroxide-Anticatalase Theory506

(B)Theory of Sevag，et al507

(C)Theory of Synergism and Antagonism508

(D)Postulation of Lee and Foley509

(E)Postulation of Jensen and Schmith509

(F)Adsorption Theories509

(G)Postulations of Henry510

(Ⅳ)CRITICAL EVALUATION OF VARIOUS THEORIES510

Chapter Ⅻ．Clinical Evaluation of Sulfonamide Drugs517

(Ⅰ)GENERAL CONSIDERATIONS517

(A)Precepts of Chemotherapy517

(Ⅱ)GENERAL INFECTIONS OF THE BODY ENDANGERING LIFE518

(A)Streptococcal Infections518

(B)Staphylococcal Infections519

(C)Pneumonia519

(D)Meningitis521

(E)Tuberculosis523

(F)Bubonic Plague526

(Ⅲ)INTESTINAL DISEASES OF BACILLARY ORIGIN526

(A)Classification of Organisms526

(B)Bacillary Dysentery526

(C)Ulcerative Colitis531

(D)Typhoid531

(E)Paratyphoid531

(F)Asiatic Cholera532

(Ⅳ)USE OF SULFONAMIDE DRUGS IN OTORHINOLARYNGOLOGY532

(A)General Remarks532

(B)Systemic Use of the Drugs in Nose and Throat Infections533

(C)Local Use of the Sulfonamides in the Upper Respiratory Tract535

(D)Otitis Media and Mastoiditis536

(E)Use of Sulfa Drugs in Ophthalmology537

(Ⅴ)SULFA DRUGS IN GENITO-URINARY INFECTIONS538

(A)Venereal Diseases538

(B)Prophylactic Use of Sulfa Drugs against Gonorrhea and Chancroid540

(C)Miscellaneous Urinary Infections541

(Ⅵ)PROPHYLACTIC USE OF SULFONAMIDES542

(A)Meningitis542

(B)Respiratory Infections543

(C)Rheumatic Fever543

(D)Bacillary Dysentery544

(E)Scarlet Fever544

(F)Drug Resistant Organisms in Prophylaxis545

(G)Drug Toxicity in Prophylaxis545

(Ⅶ)MINOR OR UNCERTAIN APPLICATIONS OF THE SULFA DRUGS546

(A)Virus Diseases546

(B)Protozoal Diseases548

(C)Fungus Diseases550

(D)Rickettsial Diseases551

(E)Local Use in Dermatology552

(F)Miscellaneous Uses553

(Ⅷ)WOUND AND SURGICAL USES OF THE SULFA DRUGS554

(A)Wounds554

(B)Burns558

(C)Abdominal Surgery559

(Ⅸ)SULFA DRUGS IN VETERINARY MEDICINE560

(Ⅹ)CLINICAL TOXICITIES563

(A)General Remarks563

(B)General Effects on the Whole Body563

(C)Toxic Reactions to the Blood563

(D)Toxic Effects on the Nervous System565

(E)Toxic Action on the Kidney566

(F)Toxic Action on the Liver569

(G)Toxic Action on the Heart569

(H)Skin Reactions569

(I)Toxic Reactions to the Eyes574

(J)Detoxification574

(K)Clinical Incidence of Toxic Reactions to the Sulfonamide Drugs(323：577)575

LIST OF JOURNALS SEARCHED578

REFERENCES579

APPENDIXES631

A．Key to Activities and Organisms or Diseases633

B．Trade Names for Sulfanilamide636

C．Trade Names for Sulfanilamide Derivatives and Related Compounds637

INDEX649