Lipinski's Rule of Five is a rule of thumb to evaluate druglikeness or determine if a chemical compound with a certain pharmacological or biological activity has properties that would make it a likely orally active drug in humans. The rule was formulated by Christopher A. Lipinski in 1997, based on the observation that most medication drugs are relatively small and lipophilic molecules.
The rule describes molecular properties important for a drug's pharmacokinetics in the human body, including their absorption, distribution, metabolism, and excretion ("ADME"). However, the rule does not predict if a compound is pharmacologically active.
The rule is important for drug development where a pharmacologically active lead structure is optimized step-wise for increased activity and selectivity, as well as drug-like properties as described by Lipinski's rule.
Lipinski's rule states that, in general, an orally active drug has no more than one violation of the following criteria:
- Not more than 5 hydrogen bond donors (nitrogen or oxygen atoms with one or more hydrogen atoms)
- Not more than 10 hydrogen bond acceptors (nitrogen or oxygen atoms)
- A molecular mass less than 500 daltons
- An octanol-water partition coefficient log P not greater than 5
Note that all numbers are multiples of five, which is the origin of the rule's name. As with many other rules of thumb, (such as Baldwin's guidelines for ring closure or Murphy's guidelines), there are many exceptions to Lipinski's Rule.
Read more about Lipinski's Rule Of Five: Improvements
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