The ability to predict the pharmalogical properties of compounds, or lack of pharmalogical properties for cosmetic use, based on their structure is important. There are specific rules that apply to predict activity.
Drug-likeness1 is a qualitative concept used in drug design for how druglike a substance is. To be an effective drug, a substance must be characterized by optimal solubility to both water and fat . Orally administered drugs must pass through the intestinal lining and be transported in aqueous blood, then penetrate the lipid cellular membrane to reach the inside of a cell. The model compound for cellulars membrane is octanol, so the logarithm of the octanol/water partition coefficient, known as log Pow, is used to estimate solubility.
Since the drug is transported in an aqueous media like blood and intracellular fluid, it has to be sufficiently water-soluble. Solubility in water can be estimated from the number of hydrogen bond donors vs. the alkyl side chains in the molecule. Low water solubility translates to slow absorption and action. Too many hydrogen bond donors, on the other hand, leads to low fat solubility, so the drug cannot penetrate the cell wall. The lower the molecular weight, the better. A total of 80% of drugs have molecular weights under 450 Dalton.
Lipinski's Rule of Five is a refinement of drug-likeness and is used to predict whether a chemical compound will have pharmacological or biological activity as an orally active drug in humans. This rule was formulated by Christopher A. Lipinski in 1997, based on the observation that most medication drugs are relatively small, lipophilic molecules.2
Lipinski's Rule of Five states that, in general, an orally active drug has:
1. Not more than 5 hydrogen bond donors (OH and NH groups);
2. Not more than 10 hydrogen bond acceptors (notably N and O);
3. A molecular weight under 500 g/mol; and
4. A partition coefficient log P less than 5
Note that all numbers are multiples of five, which is the origin of the rule's name.
1. Wikipedia Web site, available at: http://en.wikipedia.org
2. CA Lipinski, F Lombardo, BW Dominy and P J Feeney, Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Adv Drug Del Rev 46 3-26 (2001)