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AAPS 2006
San Antonio, TX, USA
October 30 - November 2, 2006
Booth #: 940
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ACD/Labs' Poster Schedule
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| Title: | Improving Solubility in Drug Candidates—A Novel Software Aided Approach to Lead Optimization |
| Authors: | Sanjivanjit K. Bhal, Karim Kassam, and Greg Pearl |
| Date: | Monday, October 30, 2006 |
| Time: | 1:00 PM - 5:00 PM |
| Location: | Exhibit Hall |
| Poster #: | M1096 |
| Abstract: |
Purpose: To demonstrate how critical inter-related molecular properties can be improved in drug candidates using a software-aided approach to structural modification in the lead optimization process.
Method: Through consideration of critical physicochemical properties of a substance, either or both pKa and logP (or logD) can be modified to influence intrinsic solubility or solubility at a relevant pH. A software tool that combines physicochemical property predictors with a database of 30,000 drug-like substituents was used to effect modifications for various physicochemical properties.
Results: We will discuss case studies that illustrate how inter-related physical properties such as pKa, logP, and logD can be modified to improve physical properties, for example, solubility (hence bioavailability). These structural modifications are carried out either through subtle alterations such as heterocyclic replacement, or functional group interchange, or more drastic changes such as addition of substituents.
Conclusion: Balancing physical properties with efficacy is critical to produce viable drug candidates. These complex properties, however, can be very difficult to adjust. Software can aid lead optimization by suggesting structural modifications based on improving molecular properties. This approach allows the chemist to quickly generate a diverse set of analogs for synthetic evaluation whilst retaining the pharmacaphore.
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This page was last updated
12 September 2007
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