Lipinski's Rule of 5 is a guideline used in drug discovery to evaluate the drug-likeness of chemical compounds. According to this rule, a compound is likely to have good oral bioavailability if it meets the following criteria:
1. Molecular Weight: Less than or equal to 500 daltons (Da).
2. LogP (Octanol-Water Partition Coefficient): Less than or equal to 5.
3. Hydrogen Bond Donors: Less than or equal to 5.
4. Hydrogen Bond Acceptors: Less than or equal to 10.
5. Total Polar Surface Area (TPSA): Less than or equal to 140 Ų.
6. Rotatable Bonds: Less than or equal to 10.
7. Synthesizability Access Score (SAS): Score value criteria.
To be considered drug-like, a compound should pass no more than one of these criteria. In other words, a drug-like compound should have:
0 or 1 violation(s) out of 7 criteria.
Molecular Weight (MW): Sum of the atomic weights of all atoms in the molecule.
LogP: The logarithm of the partition coefficient between octanol and water, indicating the compound's lipophilicity.
Hydrogen Bond Donors: Number of hydrogen atoms bound to nitrogen or oxygen.
Hydrogen Bond Acceptors: Number of nitrogen or oxygen atoms or any sulfur atom bound to hydrogen.
Total Polar Surface Area (TPSA): The surface area of polar atoms (usually oxygen and nitrogen) in the molecule.
Rotatable Bonds: Bonds that allow free rotation around themselves, usually single bonds that are not part of a ring structure.
Synthesizability Access Score (SAS): A score indicating the compound's ease of synthesis.
Remember that Lipinski's Rule of 5 is a general guideline and there are exceptions. It's a useful tool in early-stage drug discovery to filter out compounds that might have poor oral bioavailability.