Typical Types of Drug Modification

Question 1

Homologation

Answer 1

increasing compounds by a constant unit;

• hydrophobic pocket increases binding with increasing length; too large and does not fit into hydrophobic pocket
• increasing chain length increases lipophilicity and ability to cross membranes
• branched chains are less lipophilic than straight ones

Question 2

Chain Brancing

Answer 2

pharmacological changes; lowers potency if lipophilicity is important or could change activity; could interfere with receptor binding

Question 3

Bioisosterism

Answer 3

substituents or groups with chemical or physical similarities that produce similar biological properties; can attenuate toxicity, modify activity of lead, or alter pharmacokinetics of lead

Question 4

classic bioisosteres

Answer 4

peripheral layer of electrons are considered identical

Question 5

non-classic bioisosteres

Answer 5

do not have the same number of atoms; do not fit steric/electronic rules of classic isosteres