Problem 15
(a) What is the rationale for considering the following when designing a screening collection: (1) drug- or lead-like properties, (2) privileged structures, and (3) toxicophores (b) What might be a disadvantage?
Problem 16
Briefly describe the distinction between the terms "ligand-based" and "structure-based".
Problem 20
a. Design three peptidomimetics for Glu-Tyr-Val, one using a ring-chain transformation, one a scaffold peptidomimetic, and one having at least one bioisosteric replacement. b. Would you normally expect a bioisosteric replacement to improve at least one parameter (e.g., activity, safety, or pharmacokinetics) of your lead compound? Why?
Problem 21
Based on your knowledge of how the Hammett equation was developed (and basic organic mechanisms), show a mechanism and explain how a change in \(X\) will affect the rate of the following reaction.
Problem 27
Briefly describe the basis for Kuntz's DOCK program and Cramer's CoMFA.
Problem 28
For computer modeling approaches in drug design, what could be the problems associated with using a crystal structure of the target receptor without a small molecule bound to it?
Problem 29
Steric, electronic, lipophilic, and \(\mathrm{H}\)-bonding effects are important parameters of molecules employed in computer-aided drug design. Why are each of these effects important in drug design?
