Sino-American Pharmaceutical Professionals Association-New England (sapa-ne)



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Abstract

Scientists worldwide have documented that, in general, enantiomers are recognized differently by enzymes, receptors, and other binding sites in biological systems. Many studies have shown that two enantiomers of a chiral drug usually display different biological activity while one enantiomer can be detrimental. For example, Sepracor is developing several single-isomeric drugs such as, (R)-albuterol (levalbuterol), (R,R)-formoterol, (S)-oxybutynin, etc. of existing racemic drugs which display an improved therapeutic profile. Also, it has been documented that certain active metabolites of drugs display an enhanced therapeutic profile over the existing drug entities. For example, fexofenadine is an active metabolite of the former best-selling nonsedating antihistamine seldane (terfenadine). Norastemizole is a potent metabolite of antihistamine astemizole and cis-hydroxyitraconazole is an active metabolite of antifungal cis-itraconazole.


For the last few years, our group has been engaged in the development of new asymmetric methods and catalytic processes for the synthesis of drugs such as, levalbuterol, (R,R)-formoterol, (S)-oxybutynin, (S)-fexofenadine, norastemizole, cis-hydroxyitraconazole isomers, isomers of sibutramine metabolites, (R)-fluoxetine, (S)-zopicolone, (S,S)-hydroxybupropion, (S)-cetirizine, and (S)-doxazosin. This lecture will highlight several rapid synthetic approaches to produce Sepracor’s ICEs.

Biography

Dr. Chris H. Senanayake was born in Sri Lanka and received a BS degree (First Class) in Chemistry in 1982 from the University of Sri Jayawardanepura in Sri Lanka. After coming to the United States, he completed his MS at Bowling Green State University in 1983 with Professor Thomas Kinstle in synthetic chemistry. He obtained his Ph.D. under the guidance of Professor James H. Rigby at Wayne State University in 1987, where he worked on the total synthesis of complex natural products such as ophiobolanes, and completed the first total synthesis of grosshemin in the guaianolide family. He then undertook a postdoctoral fellow with Professor Carl R. Johnson and worked on the total synthesis of polyol systems such as amphotericin B and compactin analogous, and the synthesis of C-nucleoside precursors. In 1989 he joined Dow Chemical Co. as a Senior Research Chemist in the Department of Process and Development. After a brief stay at Dow Chemical, he joined the Merck Process Research Group in 1990 as a Senior Research Chemist. After a series of accomplishments in synthetic organic chemistry and obtaining a prestigious Merck Management Award in chemistry, he was promoted to Research Fellow in 1993. In 1996 he joined Sepracor, Inc. as Director of Chemical Process Research. He was promoted to Senior Director of Chemical Process Research in 1998. He is responsible for the design and development of chemical processes for the commercialization of pharmaceutical drugs.


Dr. Senanayake’s current research interests focus on the development of new asymmetric methods for the synthesis of bioactive molecules and heterocycles, and on catalytic, enzymatic, and mechanistic studies. He is the author of >75 papers and patents in several areas of synthetic organic chemistry.

Small Molecule Drug Discovery at Genzyme Corporation

Fredric J. Vinick, Ph.D., Sr. Vice President of Drug Discovery

Genzyme Corporation

1 Kendall Square

Cambridge, MA 02139

Tel: (617) 374-7272

Fax: (617) 252-7550

Email: fredric.vinick@genzyme.com



Abstract

In this presentation we describe the Genzyme approach to drug discovery, a hybrid of methods, new and old, which seeks to minimize risk/cost and maximize the output of drug candidates (novel substances which are safe and efficacious in animal models of disease). We will illustrate our strategy with data from two actual programs. We will show how Genzyme has used novel assay design and high throughput screening to discover potent new leads with potential for the treatment of cystic fibrosis. In contrast to this approach, we will also describe how the Genzyme Drug Discovery Group has selected a preclinical candidate for the treatment of lysosomal storage disorders (e.g., Gaucher’s and Fabry’s Disease) through an extremely effective chemistry/biology collaboration with an academic laboratory.


Biography
Fredric J. Vinick was educated at Williams College (B.A. in Chemistry, 1969), Yale University (Ph.D. in Organic Chemistry with Professor Harry Wasserman, 1973) and Columbia University (two years of postdoctoral research in the laboratories of Prof. Gilbert Stork). Dr. Vinick was a member of the medicinal chemistry department at Ciba Geigy Corporation from 1974-1978. He then moved to Pfizer Central Research where over the course of a sixteen-year career, he worked in the areas of exploratory process research, CNS medicinal chemistry and exploratory medicinal chemistry. As the founder and director of Pfizer's New Leads group in 1986 he helped establish high throughput screening, compound library acquisitions and high speed chemical synthesis methods. While at Pfizer Dr, Vinick contributed to patents and publications on selective phosphodiesterase inhibitors, nonpeptide substance P antagonists and bradykinin antagonists. In 1994 he assumed the position of Vice President, Drug Discovery at Genzyme Corporation. He is currently Senior Vice President of Drug Discovery. Dr. Vinick continues to have a major interest in highly efficient approaches.

Success Factors in Technology Commercialization

Roland R. Franke, Ph.D., CEO

Natural Pharmaceuticals, Inc.

100 Cummings Center, Suite 414G

Beverly MA 01915

Tel: (978) 524-8100


Fax: (978) 524-8156


Email: franke_roland@alum.mit.edu





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