Systematic, automated analysis of solubilizing groups in oral drugs

CINF 41

Paul N Mortenson, p.mortenson@astex-therapeutics.com, Miles S. Congreve, m.congreve@astex-technology.com, and Christopher W. Murray. Computational Chemistry Group, Astex Therapeutics, 436 Cambridge Science Park, Milton Road, Cambridge, CB4 0QA, United Kingdom
Medicinal chemistry programs frequently produce molecules that are potent but relatively insoluble in water. Such compounds present a range of problems, but most importantly they are unlikely to be suitable candidates for oral (or intravenous) administration. A common solution to these problems is the addition of a polar solubilising group to the molecule. We present here the results of a systematic analysis of solubilising groups present in marketed oral drugs. Proprietary software tools have been written and used to automatically extract these groups from a database of oral drugs, as well as a larger database of advanced drug candidates. A design tool has also been created that allows chemists to create virtual libraries of solubilised molecules, starting from a template that they sketch. Appropriate solubilising groups are virtually attached to the template, and the library thus created can then be further profiled for example by docking.
 

Sci-Mix
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Sci-Mix

Division of Chemical Information

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007