Contemporary Drug Synthesis

by ; ; ;
Edition: 1st
Format: Hardcover
Pub. Date: 2004-06-25
Publisher(s): Wiley-Interscience
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Summary

An integrated and insightful look at successful drug synthesis in today's drug discovery marketThe pharmaceutical industry is unquestionably vibrant today, with drug synthesis making a vital contribution. Whether in the early developmental stages of identifying and optimizing a lead, or the latter stages of process development and cost-effective scale-up, the ability to design elegant and economical synthetic routes is often a major factor in the eventual viability and commercial success of a drug.Contemporary Drug Synthesis examines how leading researchers and manufacturers have integrated chemistry, biology, pharmacokinetics, and a host of other disciplines in the creation and development of leading drugs.Authored by four of the pharmaceutical industry's most respected scientists, this timely volume: Focuses on the processes that resulted in high-profile drugs including Lipitor, Celebrex, Viagra, Gleevec, Nexium, Claritin, and over a dozen others Provides an in-depth introduction to each drug, followed by a detailed account of its synthesis Organizes the drugs into fourteen therapeutic areas for clarity and ease of use Process chemists provide an essential bridge between chemistry and the marketplace, creating scientifically practical drug processes while never losing sight of the commercial viability of those processes.Contemporary Drug Synthesis meets the needs of a growing community of researchers in pharmaceutical research and development, and is both a useful guide for practicing pharmaceutical scientists and an excellent text for medicinal and organic chemistry students.

Author Biography

JIE-JACK LI, PhD, DOUGLAS S. JOHNSON, PhD, DRAGO R. SLISKOVIC, PhD, AND BRUCE D. ROTH, PhD, are all members of Pfizer Global Research and Development, and are among the most prominent scientists working in drug discovery today.

Table of Contents

Preface v
Table of Contents
vii
Trade Names and Their Corresponding USANs xi
Acronyms and Abbreviations xiii
Antithrombotics: Ticlopidine (Ticlid®) and Clopidogrel (Plavix®)
1(10)
Introduction
1(2)
Syntheses of ticlopidine
3(1)
Syntheses of clopidogrel
4(5)
References
9(2)
Anti-inflammatory Cyclooxygenase-2 Selective Inhibitors: Celecoxib (Celebrex®) and Rofecoxib (Vioxx®)
11(10)
Introduction
11(2)
Synthesis of celecoxib
13(1)
Syntheses of rofecoxib
14(5)
References
19(2)
H+/K+-ATPase Inhibitors: Esomeprazole (Nexium®)
21(8)
Introduction
21(2)
Synthesis of esomeprazole
23(4)
Separation using HPLC
24(1)
Asymmetric oxidation of the sulfide
25(1)
Biooxidation
26(1)
References
27(2)
Protein-tyrosine Kinase Inhibitors: Imatinib (Gleevec®) and Gefitinib (Iressa®)
29(10)
Introduction to Gleevec®
29(3)
Synthesis of imatinib mesylate
32(2)
Introduction to Iressa®
34(1)
Synthesis of gefitinib
35(2)
References
37(2)
Non-sedating Antihistamines
39(16)
Introduction
39(1)
Synthesis of loratadine and desloratadine
40(3)
Synthesis of fexofenadine
43(5)
Synthesis of cetirizine
48(4)
References
52(3)
Cosmeceuticals: Isotretinoin (Accutane®), Tazarotene (Tazorac®), Minoxidil (Rogaine®), and Finasteride (Propecia®)
55(20)
Isotretinoin
56(3)
Introduction to isotretinoin
56(1)
Synthesis of isotretinoin
57(2)
Tazarotene
59(3)
Introduction to tazarotene
59(2)
Synthesis of tazarotene
61(1)
Minoxidil
62(4)
Introduction to minoxidil
62(1)
Synthesis of minoxidil
63(3)
Finasteride
66(5)
Introduction to finasteride
66(1)
Synthesis of finasteride
67(4)
References
71(4)
Antibacterials: Ciprofloxacin (Cipro®) and Linezolid (Zyvox®)
75(14)
Ciprofloxacin (Cipro®)
76(7)
Introduction to ciprofloxacin
76(3)
Synthesis of ciprofloxacin
79(4)
Linezolid (Zyvox®)
83(3)
Introduction to linezolid
83(1)
Synthesis of linezolid
84(2)
References
86(3)
Atypical Antipsychotics
89(24)
Introduction
89(4)
Synthesis of risperidone
93(3)
Synthesis of olanzapine
96(3)
Synthesis of quetiapine fumarate
99(2)
Synthesis of ziprasidone
101(6)
Synthesis of aripiprazole
107(1)
References
108(5)
Atorvastatin Calcium (Lipitor®)
113(12)
Background
113(2)
Synthesis of racemic atorvastatin
115(3)
Enantioselective syntheses of atorvastatin calcium
118(6)
References
124(1)
Antidepressants
125(24)
Background
125(3)
Synthesis of fluoxetine hydrochloride
128(5)
Synthesis of sertraline hydrochloride
133(5)
Synthesis of paroxetine hydrochloride
138(7)
References
145(4)
Anti-obesity: Orlistat (Xenical®)
149(12)
Introduction
149(3)
Synthesis of orlistat
152(6)
References
158(3)
Triptans for Migraine
161(28)
Introduction
162(1)
Synthesis of sumatriptan
163(5)
Synthesis of zolmitriptan
168(3)
Synthesis of naratriptan
171(3)
Synthesis of rizatriptan
174(3)
Synthesis of almotriptan
177(3)
Synthesis of frovatriptan
180(3)
Synthesis of eletriptan
183(3)
References
186(3)
PDE 5 Inhibitors for Erectile Dysfunction: Sildenafil (Viagra®), Vardenafil (Levitra®), and Tadalafil (Cialis®)
189(12)
Introduction
189(2)
Discovery and synthesis of sildenafil
191(4)
Synthesis of vardenafil
195(2)
Synthesis of tadalafil
197(2)
References
199(2)
Antiasthmatics
201(13)
Introduction
201(2)
Synthesis of fluticasone propionate
203(2)
Synthesis of salmeterol xinafoate
205(5)
Synthesis of montelukast sodium
210(2)
References
212(2)
Index 214

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