“Rule of Three” has been proposed for fragment molecules in fragment-based drug design (a variation on Lipinski’s Rule of Five). This alternative set of rules states that:

- Molecular weight < 300

- Hydrogen bond donors ≤ 3

- Hydrogen bond acceptors ≤ 3

- LogP ≤ 3

1. Compounds 1-3 are three of the most potent fragments from a recent screening study. For each compound, state the number of hydrogen bond donors and hydrogen bond acceptors. (3 marks)
2. Based on your donor/acceptor counts, briefly comment on the reliability of rules such as the “Rule of Three”. (1 mark)
3. What molecular property is LogP a measure of? (1 mark)

NH2 1 3