Content: Perspectives on antiallergic agents / H.F. Hodson --
The mechanism of histamine release from mast cells with reference to the action of antiallergic drugs / J.C. Foreman --
Structure-activity relationships in a new class of pyrimido[4,5-b]quinoline antiallergy agents / T.H. Althuis, S.B. Kadin, L.J. Czuba, P.F. Moore, and H.-J. Hess --
The development of phenylenedioxamic acids as potential antiallergy agents / Charles M. Hall and H.G. Johnson --
New, orally effective chromone derivatives for the treatment of asthma / H. Cairns --
Antiallergic purinones : a successful application of QSAR / K.R.H. Wooldridge --
Clinically effective 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) / Akira Nohara --
Pyranenamines : a new series of potent antiallergic compounds / K.M. Snader, L.W. Chakrin, R.D. Cramer, III, Y.M. Gelernt, C.K. Miao, D.H. Shah, B.M. Sutton, J.W. Venslavsky, and C.R. Willis --
The development of antiallergic pyranenamine series : a QSAR success story / Richard D. Cramer, III, Kenneth M. Snader, Chester R. Willis, Lawrence W. Chakrin, Jean Thomas, and Blaine M. Sutton --
Oxatomide : the prototype of a chemical series of compounds inhibiting both the release and the effects of allergic mediators / F. Awouters, C.J.E. Niemegeers, P.A. Janssen, M. Janssen, J. Vandenberk, L. Kennis, M. Van Der Aa, and A. Van Heertum --
Bronchodilators and other pharmacodynamic agents / Davis L. Temple, Jr. --
Pathophysiologic derangements in the chronic obstructive pulmonary diseases and pharmacologic regulation of airway function / Sanford Chodosh --
New aspects of [beta]-adrenergic bronchodilator drugs / Carl Kaiser --
Recent innovations in theophylline-like bronchodilator drugs / Richard J. Seidehamel and Davis L. Temple, Jr. --
Prospects for a prostaglandin bronchodilator / Charles V. Grudzinskas, Jerauld S. Skotnicki, Sow-Mei L. Chen, M. Brawner Floyd, Jr., William A. Hallett, Robert E. Schaub, Gerald J. Siuta, Allan Wissner, Martin J. Weiss, and Franz Dessy.
Author(s): Davis L. Temple, Jr. (Eds.)
Series: ACS Symposium Series 118
Publisher: American Chemical Society
Year: 1980
Language: English
Pages: 390
City: Washington, D.C
Title Page......Page 1
Half Title Page......Page 3
Copyright......Page 4
ACS Symposium Series......Page 5
FOREWORD......Page 6
PdftkEmptyString......Page 0
PREFACE......Page 7
1 Introduction: Perspectives on Antiallergic Agents......Page 9
Mechanism of Mediator Release......Page 19
Mechanism of Action of Antiallergic Drugs......Page 34
Literature Cited......Page 40
3 Structure-Activity Relationships in a New Class of Pyrimido[4,5-b]quinoline Antiallergy Agents......Page 43
The Discovery of Ethyl 3,4-Dihydro-4-oxopyrimido[4,5-b]quinoIine-2-carboxylate......Page 44
Chemistry of 3,4-Dihydro-4-oxopyrimido[4,5-b]quinoline-2-carboxylic Acids......Page 46
Pyrimido[4,5-b]quinoline SAR......Page 49
Classes of Experimental Agents Orally Effective in the Rat PCA Procedure......Page 57
Summary......Page 69
Literature Cited......Page 70
4 The Development of Phenylenedioxamic Acids As Potential Antiallergy Agents......Page 75
A. Rat Studies.......Page 77
B. Mechanism of Cholinergic Stimulation at High Concentrations of U-42,585E (lodoxamide tromethamine).......Page 84
The Effect of Pretreatment of Rats with the Muscarinic Blockers Atropine and Quinuclidinyl Benzilate (QNB) on Multiple Dose DSCG and Lodoxamide Tromethamine Tachyphylaxis......Page 88
C. Comparison Between Cromolyn Sodium and Lodoxamide Tremethamine in Primates Against Aerosolized Ascaris suum Antigen.......Page 93
D. Human Clinical Studies With Lodoxamide Tromethamine.......Page 96
Literature Cited:......Page 102
5 New, Orally Effective Chromone Derivatives for the Treatment of Asthma......Page 104
LITERATURE CITED......Page 120
6 Antiallergic Purinones: A Successful Application of QSAR......Page 121
LITERATURE CITED......Page 127
7 Clinically Effective 6-Ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344)......Page 128
Structure-Activity Relationships in the Tetrazole (5) and Acrylic Acid (4) Series (22, 16)......Page 130
Metabolic Fate of AA-344 (29)......Page 135
Synthesis and Biological Activities of the Metabolites (32)......Page 138
Clinical Trials......Page 142
Literature Cited......Page 145
Introductory Chemistry......Page 148
Monosubstituted Pyranenamines......Page 149
Multiply Substituted Pyranenamines......Page 151
In Vitro Evaluation of Candidates......Page 156
"Literature Cited"......Page 161
9 The Development of Antiallergic Pyranenamine Series: A QSAR Success Story......Page 162
References and Footnotes......Page 181
10 Oxatomide: The Prototype of a Chemical Series of Compounds Inhibiting Both the Release and the Effects of Allergic Mediators......Page 182
Chemistry......Page 183
Materials, Methods and Results.......Page 190
Studies in Rats......Page 197
Materials, Methods and Results.......Page 198
Studies in Dogs......Page 202
Materials, Methods and Results.......Page 204
General Conclusions......Page 208
Literature Cited......Page 209
11 Introduction: Bronchodilators and Other Pharmacodynamic Agents......Page 212
Chronic Obstructive Lung Disease......Page 217
Common Physiologic Abnormalities......Page 218
Chronic Bronchitis......Page 219
Chronic Bronchial Asthma......Page 230
Pulmonary Emphysema.......Page 244
Literature Cited......Page 248
13 New Aspects of β-Adrenergic Bronchodilator Drugs......Page 250
Pharmacology Methods (30)......Page 252
Structure-Activity Relationships......Page 253
Conformational Analysis of β-Adrenergic Receptor Agonists (50)......Page 270
Acknowledgments......Page 274
Literature Cited......Page 275
14 Recent Innovations in Theophylline-Like Bronchodilator Drugs......Page 283
Literature Cited......Page 295
I. Introduction......Page 298
II. Total Synthesis By The Conjugate Addition Procedure......Page 299
A. Cyclopentenone Precursors to 11-Deoxyprostaglandins......Page 301
B. Cyclopentenolone Precursors to 11-Oxy and 11-Thio Prostaglandins......Page 307
C. The Conjugate Addition Step. Preparation Of The Organometallic Reagents......Page 310
1. 15-Deoxy Series......Page 315
4. 15-Hydroxy β-Chains Potentially Resistant To PG 15-Dehydrogenase.Introduction......Page 316
a. 15-Hydroxy-15-alkyI Series......Page 317
c. 15-Hydroxy-16,16-Dialkyl Series......Page 319
d. 15-Hydroxy-17,17-Dialkyl Precursor......Page 321
f. 15-Hydroxy-16-Methoxy Series......Page 323
a. Introduction......Page 324
6. 13-Thia Series......Page 326
A. 11-Deoxy-11-Substituted Analogs......Page 329
B. C9 Derivatives: Hydrazones and Ketals of 11-Deoxy-13,14-dihydro-PGE1......Page 331
C. C1-Derivatives: Amides and Esters......Page 332
IV. Bronchodilator Assays......Page 333
A. 11-And 15-Hydroxy Groups......Page 334
Β. C11-Substitution......Page 335
3. 9-Deoxy Derivatives......Page 339
D. 10a-Homo Series......Page 341
1. 13,14-dihydro Analogs......Page 342
VI. α-Chain Variations......Page 343
Β. 3-Thia and 3-Oxa Series......Page 344
C. Variation in Chain Length and Double Bond Isomerization......Page 346
VII. β-Chain Modifications......Page 347
B. 16,16-Dimethyl Derivatives......Page 348
C. Cycloalkyl Derivatives......Page 351
D. Other C16 Substitutents......Page 354
F. 15-Deoxy-16-Hydroxy Series......Page 355
VIII. Prostacyclins......Page 361
IX. Summary and Critique......Page 362
LITERATURE CITED......Page 366
A......Page 375
B......Page 377
C......Page 378
D......Page 380
E......Page 381
H......Page 382
L......Page 383
M......Page 384
P......Page 385
R......Page 388
T......Page 389
X......Page 390
