ABSTRACT
Natural products have had a profound impact on the discovery and development of medicinal agents throughout history.1 In the two centuries since Friedrich Sertürner rst isolated morphine (1) from opium,2 there have been a signicant number of novel natural products revealed and elucidated that have played a crucial role in preventing disease and treating symptoms. From anti-infective agents such as penicillin (2)3 and erythromycin (3)4 to anticancer compounds such as vincristine (4)5 and Taxol (5),6 countless human lives have been saved through the auspices of natural product drugs. Even today, some diseases, such as malaria, are predominantly treated with natural products like artemisinin (6).7 In addition, some compounds play a prominent role in the elucidation of critical biological pathways that can be exploited in the treatment of a number of conditions. For
CONTENTS
14.1 Introduction .......................................................................................................................... 393 14.2 Lead Optimization ................................................................................................................ 395
14.2.1 Pharmacokinetics in Lead Optimization .................................................................. 396 14.2.1.1 Absorption.................................................................................................. 398 14.2.1.2 Distribution ................................................................................................ 399 14.2.1.3 Metabolism ................................................................................................400 14.2.1.4 Excretion ....................................................................................................402
