Chapter 3
(1) See Section 3.1.
(2) See Section 3.2.1. (i) Replacing a rigid structure by an equivalent sized rigid
structure gives a better chance of an active analogue. The shape of a rigid structure
may give information about the size and shape of its receptor provided the rigid part
of the molecule is the part that binds to the receptor. If the part of a ligand that
binds to the receptor is a rigid structure it can also indicate the best conformation
for analogues to bind to the receptor.(4) (ii) Different conformations can result in different activities and potencies.
(4)(iii) See section 3.2.3 and Table 2.1.
(3) Compounds that are reasonably water soluble are more easily absorbed, trans-
ported to their site of action and eliminated from the body.
(4) (i) High polar group to carbon atom ratio (see section 3.4).
(4)(ii) The presence of polar groups that can hydrogen bond to water molecules and
ionize in water (see section 3.4 and Figure 3.5).
(5) (i) Form salts that would improve water solubility but would break down to yield
the drug in the biological system (see section 3.5).
(4) (ii) Introduce water solubilizing groups into a part of the structure that is not the
pharmacophore of the drug (see section 3.6).
(4)(iii) The use of special dosage forms (see section 3.4).
(6) See Figure 3.6. for methods
(4) (i) O-acylation with succinic anhydride.
(4)(ii) O- or N-alkylation with an appropriate reagent.
Chapter 4
(1) Structure–activity relationship. SARs are the general relationships obtained from a
study of the changes in activity with changes in the structure of a lead. These
changes are used to find or predict the structure with the optimum activity. For
example, see Figure 4.1.(2) (i) See Table 4.2. (ii) CF 3. It is approximately the same size as a chlorine atom.
ANSWERS TO QUESTIONS 263