Druglikeness (Paperback)

Please note that the content of this book primarily consists of articles available from Wikipedia or other free sources online. High Quality Content by WIKIPEDIA articles Druglikeness is a qualitative concept used in drug design for how "druglike" a substance is with respect to factors like bioavailability. It is estimated from the molecular structure before the substance is even synthesized and tested. A druglike molecule has properties like this: Optimal solubility to both water and fat, because an orally administered drug has to go through the intestinal lining, carried in aqueous blood and penetrate the lipid cellular membrane to reach the inside of a cell. The model compound for the cellular membrane is octanol, so the logarithm of the octanol/water partition coefficient, known as ClogP, is used to estimate solubility. Since the drug is transported in aqueous media like blood and intracellular fluid, it has to be sufficiently water-soluble in the absolute sense. Solubility in water can be estimated from the number of hydrogen bond donors vs. alkyl sidechains in the molecule. Low water solubility translates to slow absorption and action. Too many hydrogen bond donors, on the other hand, lead to low fat solubility, so that the drug cannot penetrate the cell wall to reach the inside of the cell.