Strategies for Organic Drug Synthesis and Design

by Lednicer, Daniel

• ISBN13: 9780470190395
• ISBN10: 0470190396
• Edition: 2nd
• Format: Hardcover
• Copyright: 2008-10-27
• Publisher: Wiley-Interscience

Summary

This book examines and evaluates the strategies utilized to design and synthesize pharmaceutically active agents. Significant updates over the last 10 years since the publication of the 1st edition include synthesis of enantiomerically pure isomers, novel chemical methodologies, and new pharmaceutical agents targeted at novel biological endpoints. Written by an experienced successful author, this book meets the needs of a growing community of researchers in pharmaceutical R &D, as well as medical professionals, by providing a useful guide for designing and synthesizing pharmaceutical agents. Additionally, it is a useful text for medicinal chemistry students.

Author Biography

Daniel Lednicer, PhD, is the acclaimed author of several books on drug synthesis and discovery. His career has been devoted to the search for new therapeutic agents. Dr. Lednicer spent two decades at the bench as a chemist at the Upjohn Company. He has also served as director of chemical research at Mead Johnson, director of pharmaceutical sciences at Adria Laboratories, and pharmaceutical manager at Analytical Biochemistry Laboratories. Most recently, he was a project officer at the National Cancer Institute.

Table of Contents

Preface	p. xv
Prostaglandins, Peptidomimetic Compounds, and Retinoids	p. 1
Prostaglandins	p. 1
Peptidomimetic Compounds	p. 19
Protease Inhibitors	p. 19
Introduction	p. 19
Renin Inhibitors	p. 20
Antiviral Compounds	p. 22
Fibrinogen Receptor Antagonists	p. 30
Antitumor Peptidomimetic	p. 34
Retinoids	p. 35
A Miscellaneous Drug	p. 38
References	p. 40
Drugs Based on a Substituted Benzene Ring	p. 43
Arylethanolamines	p. 43
Aryloxypropanolamines	p. 54
[beta]-Blockers	p. 54
Non-Tricyclic Antidepressants (SSRIs)	p. 57
Arylsulfonic Acid Derivatives	p. 61
Antibacterial Sulfonamides	p. 61
Diuretic Agents	p. 63
Oral Hypoglycemic Agents	p. 65
Miscellaneous Arylsulfonamides	p. 70
Arylacetic and Arylpropionic Acids	p. 71
Arylacetic acid "Fenacs"	p. 71
Arylpropionic Acid "Profens"	p. 75
Arylacetamide Antiarrhythmic Compounds	p. 78
Leukotriene Antagonists	p. 81
Miscellaneous Compounds	p. 84
References	p. 86
Indenes, Naphthalenes, and Other Polycyclic Aromatic Compounds	p. 89
Indenes	p. 90
Naphthalenes	p. 94
Antifungal Agents	p. 94
Miscellaneous Naphthalenes	p. 97
Partly Reduced Naphthalenes	p. 99
Bicyclic Retinoids	p. 99
Another [beta]-Blocker	p. 101
Aminotetralin CNS Agents	p. 102
Tricyclic Compounds	p. 105
Dibenzocycloheptane and Dibenzocycloheptene Antidepressants	p. 105
Antidepressants Based on Dihydroanthracenes	p. 110
Anthraquinones: The "Antrone" Chemotherapy Agents	p. 113
References	p. 116
Steroids: Part 1: Estranes, Gonanes, and Androstanes	p. 119
Introduction	p. 119
Steroid Starting Materials	p. 120
From Diosgenin	p. 121
From Soybean Sterols	p. 121
Estranes	p. 123
Synthesis of Estranes	p. 123
Drugs Based on Estranes	p. 125
Gonanes, the 19-nor Steroids	p. 128
Progestational Compounds	p. 128
Progesterone Antagonists	p. 137
Androgenic Compounds	p. 140
Androstanes	p. 142
Starting Materials	p. 142
Androgenic Compounds	p. 143
Antiandrogens	p. 150
Aldosterone Antagonists	p. 153
References	p. 157
Steroids; Part 2: Compounds Related to Progesterone, Cortisone, and Cholesterol	p. 161
Introduction	p. 161
Progestins	p. 161
Corticosteroids	p. 169
Compounds Derived from Cholesterol	p. 186
References	p. 189
Nonsteroidal Sex Hormones and Their Antagonists	p. 191
Introduction	p. 191
Estrogens	p. 191
Nonsteroidal Estrogens	p. 191
Nonsteroid Estrogen Antagonists	p. 195
Arylethylenes	p. 195
Carbocyclic Ethylenes Fused to a Benzene Ring	p. 200
Heterocyclic Ethylenes Fused to a Benzene Ring	p. 203
Nonsteroid Androgen Antagonists	p. 207
A Nonsteroid Progestin Agonist	p. 209
References	p. 210
Opioid Analgesics	p. 213
Introduction	p. 213
Drugs Derived from Morphine	p. 214
Compounds Prepared from Thebaine	p. 216
Morphinans	p. 219
Benzomorphans	p. 223
Analgesics Based on Nonfused Piperidines	p. 226
4-Arylpiperidines: Meperidine and Its Analogues	p. 226
4-Amidopiperidines: Compounds Related to Fentanyl	p. 229
Miscellaneous Compounds	p. 234
1,2-Bisaminoceclohexanes	p. 234
Open Chain Compounds	p. 236
References	p. 237
Drugs Based on Five-Membered Heterocycles	p. 239
Introduction	p. 239
Rings that Contain One Heteroatom	p. 239
Furans	p. 239
Pyrrole and Its Derivatives	p. 241
NSAIDS and a "Statin"	p. 241
ACE Inhibitors	p. 246
Miscellaneous Compounds	p. 251
Rings that Contain Two Heteroatoms	p. 258
Cyclooxygenase 2 (COX-2) Inhibitor NSAIDs	p. 258
Oxazoles, Isoxazoles, and their Derivatives	p. 262
Imidazoles	p. 269
Imidazolines	p. 287
Modified Imidazoles	p. 291
Pyrrazolones and Pyrrazolodiones	p. 295
Thiazoles and Related Sulfur-Nitrogen-Containing Heterocycles	p. 298
Rings that Contain Three or More Heteroatoms	p. 304
1,2,4-Oxadiazoles	p. 304
Triazoles	p. 306
Thiadiazoles	p. 311
Tetrazoles	p. 313
References	p. 314
Drugs Based on Six-Membered Heterocycles	p. 319
Rings that Contain One Heteroatom	p. 319
Pyrans	p. 319
Pyridines	p. 323
1,4-Dihydropyridines	p. 329
Piperidines	p. 332
Psychotropic Compounds	p. 332
Miscellaneous Piperidines	p. 336
Pyridones and Glutarimides	p. 337
Rings that Contain Two Heteroatoms	p. 341
Pyridazines	p. 341
Pyrimidines	p. 344
Antibacterial Agents	p. 344
Antiviral and Antineoplastic Pyrimidines	p. 348
Miscellaneous Pyrimidines	p. 356
Pyrimidones	p. 359
Triketopyrimidines: The Barbiturates	p. 363
Pyrazines	p. 364
Piperazines	p. 366
Rings Containing Three Heteroatoms: The Triazines	p. 376
References	p. 379
Five-Membered Heterocycles Fused to a Benzene Ring	p. 383
Compounds that Contain One Heteroatom	p. 383
Benzofurans	p. 383
Indoles	p. 389
Indolines and Isoindolines	p. 401
Compounds that Contain Two Heteroatoms	p. 407
Indazoles	p. 407
Benzimidazoles	p. 408
Benzoxazoles and Benzisoxazoles	p. 419
Benzothiazoles	p. 421
Compounds that Contain Three Heteroatoms	p. 423
References	p. 425
Six-Membered Heterocycles Fused to a Benzene Ring	p. 429
Compounds that Contain One Heteroatom	p. 429
Coumarins	p. 429
Chromones	p. 432
Benzopyrans	p. 435
Quinolines	p. 440
Antimalarial Compounds	p. 440
Other Quinolines	p. 444
Quinolones	p. 454
Antibacterial Agents	p. 454
Miscellaneous Quinolones	p. 462
Isoquinoline and Its Derivatives	p. 463
Compounds that Contain Two Heteroatoms	p. 467
Benzodioxans	p. 467
Miscellaneous Fused Rings that Include Oxygen	p. 470
Cinnolines and Phthalazines	p. 472
Quinazolines	p. 476
Quinazolones	p. 482
Compounds that Contain Three Heteroatoms	p. 488
References	p. 490
Seven-Membered Heterocyclic Rings Fused to Benzene	p. 495
Compounds with a Single Heterocyclic Atom	p. 495
Compounds with Two Heteroatoms	p. 499
Benzodiazepine Anxiolytic Agents	p. 499
Other Seven-Membered Heterocycles Fused to a Benzene Ring	p. 508
References	p. 513
Heterocycles Fused to Two Aromatic Rings	p. 515
Compounds Containing a Single Heteroatom	p. 515
Derivatives of Dibenzopyran and Dibenzoxepin	p. 515
Dibenzo Heterocycles Containing One Ring Nitrogen Atom	p. 520
Dibenzo Heterocycles with One Sulfur Atom	p. 527
Compounds Containing Two Heteroatoms	p. 532
Phenothiazines	p. 532
A Dibenzoxazine	p. 535
Dibenzodiazepines, Dibenzoxazepines, and a Dibenzothiazepine	p. 536
Pyridine-Based Fused Tricyclic Compounds	p. 540
References	p. 543
Beta Lactam Antibiotics	p. 545
Penicillins	p. 546
Cephalosporins	p. 558
Monobactams	p. 572
References	p. 574
Heterocycles Fused to Other Heterocyclic Rings	p. 577
Two Fused Five-Membered Rings	p. 577
Five-Membered Heterocycles Fused to Six-Membered Rings	p. 580
Compounds Containing Two Heteroatoms	p. 580
Compounds Containing Three Heteroatoms	p. 586
Compounds with Four Heteroatoms	p. 593
Purines	p. 593
Two Fused Six-Membered Rings	p. 611
Compounds Related to Methotrexate	p. 611
Other Fused Heterocyclic Compounds	p. 615
Heterodiazepines	p. 620
Heterocyclic Compounds with Three or More Rings	p. 622
References	p. 629
Subject Index	p. 633
Reaction Index	p. 651
Cross Index of Biological Activities	p. 671
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