THE ART OF DRUG SYNTHESIS

1 THE ROLE OF MEDICINAL CHEMISTRY IN DRUG DISCOVERY 1
2 PROCESS RESEARCH: HOW MUCH? HOW SOON? 11
3 AROMATASE INHIBITORS FOR BREAST CANCER: EXEMESTANE (AROMASIN), ANASTROZOLE (ARIMIDEX), AND LETROZOLE (FEMARA) 31
4 QUINOLONE ANTIBIOTICS: LEVOFLOXACIN (LEVAQUIN), MOXIFLOXACIN (AVELOX), GEMIFLOXACIN (FACTIVE), AND GARENOXACIN (T-3811) 39
5 TRIAZOLE ANTIFUNGALS: ITRACONAZOLE (SPORANOX), FLUCONAZOLE (DIFLUCAN), VORICONAZOLE (VFEND), AND FOSFLUCONAZOLE (PRODIF) 71
6 NON-NUCLEOSIDE HIV REVERSE TRANSCRIPTASE INHIBITORS 83
7 NEURAMINIDASE INHIBITORS FOR INFLUENZA: OSELTAMIVIR PHOSPHATE (TAMIFLU) AND ZANAMIVIR (RELENZA) 95
8 PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR) AGONISTS FOR TYPE 2 DIABETES 117
9 ANGIOTENSIN AT1 ANTAGONISTS FOR HYPERTENSION 129
10 LEADING ACE INHIBITORS FOR HYPERTENSION 143
11 DIHYDROPYRIDINE CALCIUM CHANNEL BLOCKERS FOR HYPERTENSION 159
12 SECOND-GENERATION HMG-CoA REDUCTASE INHIBITORS 169
13 CHOLESTEROL ABSORPTION INHIBITORS: EZETIMIBE (ZETIA) 18314 DUAL SELECTIVE SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS (SSNRIs) FOR DEPRESSION 199
15 GABAA RECEPTOR AGONISTS FOR INSOMNIA: ZOLPIDEM (AMBIEN), ZALEPLON (SONATA), ESZOPICLONE (ESTORRA, LUNESTA), AND INDIPLON 215
16 Alpha2Delta LIGANDS: NEURONTIN (GABAPENTIN) AND LYRICA (PREGABALIN) 225
17 APPROVED TREATMENTS FOR ATTENTION DEFICIT HYPERACTIVITY DISORDER: AMPHETAMINE (ADDERALL), METHYLPHENIDATE (RITALIN), AND ATOMOXETINE (STRATERRA) 241

The Art of Drug Synthesis illustrates how chemistry, biology, pharmacokinetics, and a host of other disciplines come together to produce successful medicines. The authors have compiled a collection of 21 representative categories of drugs, from which they have selected as examples many of the best-selling drugs on the market today. An introduction to each drug is provided, as well as background to the biology, pharmacology, pharmacokinetics, and drug metabolism, followed by a detailed account of the drug synthesis.
• Edited by prominent scientists working in drug discovery for Pfizer
• Meets the needs of a growing community of researchers in pharmaceutical R&D
• Provides a useful guide for practicing pharmaceutical scientists as well as a text for medicinal chemistry students
• An excellent follow-up to the very successful first book by these editors, Contemporary Drug Synthesis, but with all new therapeutic categories and drugs discussed.

Authors
• Douglas S. Johnson, PHD, is a Research Chemist at Pfizer Global Research and Development.
• Jie Jack Li, PHD, is a Research Chemist at Pfizer Global Research and Development.