ACD/Labs AAPS Seminar Best Western Garden Inn, Salt Lake City, UT, USA October 26, 2003 Best Western Garden Inn 154 West 600 South Salt Lake City, UT

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Agenda

Sunday, October 26, 2003

Strategies for Improving Aqueous Solubility within a Lead Optimization Series

Hosted by: Robert S. DeWitte, Ph.D., Director, Medicinal Chemistry Solutions, ACD/Labs

1:00 Dessert Reception

1:45 Introduction & Welcome

2:00 An overview of ACD/Labs Software Solutions:

A brief introduction to the products offered by Advanced Chemistry Development and how they couple together to form solutions for many of today's challenges in Analytical Chemistry, Patenting and Publishing, and Pharmaceutics.

2:20 Solubility for Discovery versus Solubility for Development:

A pragmatic view of research practices in these two areas of pharmaceutical R&D, and how these habits affect the nature of the sample, the technique of measurements, and the meaning of the results. In particular, the problem of solubility will be dissected into two separate issues: how insoluble compounds confound in vitro and in vivo testing, and how insoluble compounds limit oral bioavailability.

2:40 Solubility is two phenomena:

An elementary review of the physical basis of solubility.

3:00 Working hypotheses for improving solubility:

This session is designed to employ the items covered in the first hour to identify two vectors along which to design synthetic analogues in order to improve aqueous solubility. By the coffee break, attendees should have a conceptual understanding of what types of physicochemical changes they would like to introduce in their compound series in order to drive toward more soluble compounds.

3:20 Coffee Break

This session will be a live tutorial using ACD/PhysChem prediction as a guide in designing structural modifications to achieve the physicochemical design goals illuminated before the coffee break. Attendees will be shown how to deduce chemical modifications by predicting pK_a's and logP's of analogues and studying the calculation protocols. The result will be a set of specific chemical analogues that should be tested for improved solubility.

4:00 A role for measurements:

This session digs a little deeper into how the ACD/PhysChem calculations work at the algorithmic level and explores the synergy between targeted measurements and prediction.

4:30 Conclusion