Chiral Drugs: Chemistry and Biological Action

An integrated view of chiral drugs from concept andsynthesisto pharmaceutical properties

Chirality greatly influences a drug′s biological andpharmacological properties. In an effort to achieve morepredictable results from chiral drugs, the Food and DrugAdministration now requires that these medicines be as pure aspossible, which places great demands on drug synthesis,purification, analysis, and testing. To assist researchers inacquiring the essential knowledge to meet these rigid guidelines,Chiral Drugs focuses on three vital chiraltechnologies asymmetric synthesis, biocatalytic process, andchiral resolution to offer details on the basic concepts, keydevelopments, and recent trends in chiral drug discovery, alongwith:

The history of chiral drugs development and industrialapplications of chiral technologies

A section listing twenty–five approved or advanced–trial chiraldrugs that lists each drug name, chemical name and properties, arepresentative synthetic pathway, pharmacologicalcharacterizations, and references

An interdisciplinary approach combining synthetic organicchemistry, medicinal chemistry, and pharmacology

Nearly two–thirds of the drugs on today′s market are chiraldrugs. Reducing and eliminating their negative characteristics isan ongoing and serious challenge for the pharmaceutical industry.With its well–balanced approach to covering each important aspectof chirality, Chiral Drugs champions important strategies fortipping the medical scale in a positive direction for theproduction of more effective and safer drugs.

ABOUT THE EDITORS vii

CONTRIBUTORS ix

INTRODUCTION 1

1 OVERVIEW OF CHIRALITY AND CHIRAL DRUGS 3
Guo–Qiang Lin, Jian–Ge Zhang, and Jie–Fei Cheng

2 CHIRAL DRUGS THROUGH ASYMMETRIC SYNTHESIS 29
Guo–Qiang Lin and Xing–Wen Sun

3 CHIRAL DRUGS VIA BIOCATALYTICAL APPROACHES 77
Jianqiang Wang and Wenya Lu

4 RESOLUTION OF CHIRAL DRUGS 137
Qi–Dong You

5 FLUORINE–CONTAINING CHIRAL DRUGS 195
Xiao–Long Qiu, Xuyi Yue, and Feng–Ling Qing

6 INDUSTRIAL APPLICATION OF CHIRAL TECHNOLOGIES 253
Hui–Yin (Harry) Li, Rui Liu, Carl Behrens, and Chao–YingNi

7 STRUCTURAL BASIS AND COMPUTATIONAL MODELING OF CHIRAL DRUGS297
Deping Wang and Eric Hu

8 PHARMACOLOGY OF CHIRAL DRUGS 323
Yongge Liu and Xiao–Hui Gu

9 PHARMACOKINETICS OF CHIRAL DRUGS 347
Hanqing Dong, Xiaochuan Guo and Zengbiao Li

10 TOXICOLOGY OF CHIRAL DRUGS 381
Guang Yang and Hai–Zhi Bu

11 REPRESENTATIVE CHIRAL DRUGS 401
Jiangqin Sun, Dingguo Liu, and Zhimin Wang

INDEX 449

GUO–QIANG LIN, is a professor at the Shanghai Institute ofOrganic Chemistry and an adjunct professor at Fudan University,China. He is the Director of the Division of Chemical Science ofthe National Natural Science Foundation of China. Among ProfessorLin′s publications are the Wiley books Principles and Applicationsof Asymmetric Synthesis and Biocatalysis for the PharmaceuticalIndustry.

QI–DONG YOU, PHD, is the Dean and a professor of theSchool of Pharmacy at China Pharmaceutical University. He is anAssociate Editor of Progress in Pharmaceutical Sciences and serveson the Editorial Board of the International Journal of MedicinalChemistry and Acta Pharmaceutica Sinica. Dr. You is a coauthor ofover eighty publications, and an inventor or co–inventor of overtwenty patent applications and patents.

JIE–FEI CHENG, PHD, is the Director of Otsuka Shanghai ResearchInstitute, a fully owned subsidiary of Otsuka Pharmaceutical Co.,Ltd Japan. Formerly an associate professor at Shanghai Institute ofOrganic Chemistry, he has worked for over fifteen years in thepharmaceutical and biotech industries in the United States. Dr.Cheng is a coauthor of over fifty peer–reviewed publications, andan inventor or coinventor of over twenty patent applications andpatents.

The book can be recommended to all those who areinterested in this important and fast–growing field of research atthe interface of chemistry, pharmacy, and medicine of the basicconcepts behind modern biological psychiatric research and therecent history of the field.   (ChemMedChem,2012)