The Ups and Downs in Drug Design

Rezensionen / Stimmen

In this book, Dr. Marquez goes to great lengths to explain the chemical rationales that he and his teams followed including the development and utilization of efficient synthetic schemes and the molecular mechanisms of action of the potential drug candidates that they pursued. The stories that Dr. Marquez relates illustrate the challenges they faced, the joys of the successes and the frustrations of the defeats in drug discovery. More importantly, they guide the reader through the thought processes and what was learned in each of these efforts even when the success was less than hoped for. This book is a wonderful lesson for those bright young minds who are considering careers in the biomedical sciences as well as those already on the pathway and indeed experienced practitioners too.

- George A. Garcia, from the Foreword

The purpose of this book is to describe Dr. Marquez's journey/career in medicinal chemistry in a semi-autobiographical function. As it follows his own personal journey, the "chapters" seem random as they parallel his career path and the work/molecules he studied. It is a rather unique text as a career "summary" for Dr. Marquez.

In my opinion as a pharmacy educator, the target audience of this book is primarily colleague medicinal chemists who can relate to the changes in the field over the past four decades. Graduate-level students in this field also may admire the pathway and trials and tribulations of a mentoring medicinal chemist. Based on his longstanding career, Dr. Marquez is a leader in this field and an educator.

This is the first book of this style I have come across in my academic career. As the book is based on Dr. Marquez' personal journal, it is rather unique, but a second edition will not apply.

- Patrick J. McDonnell, PharmD (Temple University School of Pharmacy) The purpose of this book is to describe Dr. Marquez's journey/career in medicinal chemistry in a semi-autobiographical function. As it follows his own personal journey, the "chapters" seem random as they parallel his career path and the work/molecules he studied. It is a rather unique text as a career "summary" for Dr. Marquez.

In my opinion as a pharmacy educator, the target audience of this book is primarily colleague medicinal chemists who can relate to the changes in the field over the past four decades. Graduate-level students in this field also may admire the pathway and trials and tribulations of a mentoring medicinal chemist. Based on his longstanding career, Dr. Marquez is a leader in this field and an educator.

This is the first book of this style I have come across in my academic career. As the book is based on Dr. Marquez' personal journal, it is rather unique, but a second edition will not apply.

- Patrick J. McDonnell, PharmD (Temple University School of Pharmacy)

This engaging career history by one of the most accomplished and illustrious chemists to work at the National Cancer Institute (NCI) outside of Washington, DC is well worth the read for professional medicinal chemists. It probes the career path of Victor E. Marquez, in his various long-term projects aimed at finding treatments for cancer, malaria, viral infections, immune disorders and other diseases. Early on, during his graduate studies at the University of Michigan (Ph.D., 1970), he was introduced to compounds that interact directly or indirectly with nucleic acids and maintained that focus throughout his career, recognizing the tremendous potential of this area for future therapeutics. Marquez is currently Scientist Emeritus at NCI and remains active in lecturing and writing. His story is also a personal story from his origins in Venezuela, where his father founded and mother helped manage the most prominent pharmaceutical company in Venezuela, to the US and then back and forth, eventually spending most of his career at NCI.

Important topics covered include mechanism-based design of biologically active molecules, when that was not yet popular in mainstream science, inhibitors of cytidine deaminase, conformational control of transition state mimics for enzyme inhibitors, and phosphate analogues that are resistant to hydrolysis. Although initially met with skepticism, Marquez's concept of "locking" nucleoside conformation is fully embraced by the medicinal chemistry community and has revolutionized the field of nucleoside structure activity relationships (SAR).

This autobiography is not only a delightful read, it is scientifically informative about the origins of many aspects of nucleic acid chemistry that we now take for granted. This volume can be a model for early-stage researchers of how to successfully advance a career in medicinal chemistry. It's no wonder that Marquez successfully mentored >40 postdoctoral fellows, many of whom have become well-known academic and pharma scientists. Dr. Marquez also shares behind the scenes vignettes leading to either success or failure of his efforts, often for administrative and non-technical reasons. I recommend it highly to anyone in the drug discovery field.

- Kenneth A. Jacobson, Ph.D. NIDDK, NIH