Fundamentals of Medicinal Chemistry

(3) See Section 4.3.2 and Table 4.3 for both parts (i) and (ii).

(4) See Table 4.2 for all the answers to parts (i)–(iii).

(5) See Section 4.4.

(6) Lipophilicity: see section 4.4.1 (Pandp). Shape: see section 4.4.3 (Esand MR).

Electronic effects: see section 4.4.2 (s).

(7) (a) See Section 4.4.4.

(7)(b) (i)n¼the number of compounds used to derive the equation;s¼the standard

deviation for the equation;r¼the regression constant, the nearer its value

to units the better the fit of the data to the Hansch equation. Equations are

normally said to have an acceptable degree of accuracy ifris greater than

0.9.

(7) (ii) See Section 4.4.4 and in particular Equation (4.11).

(7) (iii) A more polar substituent would have a negativepvalue (see Table 4.4),

which could reduce the activity of the compound.

(8) (a) See Section 4.4.4.1

(b) Substituents in the upper right hand corner of Figure 4.6.

(9) (i) See Section 4.5.

(ii) Can only be used for substituents listed in the two decision trees.

The lead compound must have an unfused aromatic ring.

It requires a rapid method of assessing the biological activity of the lead and its

analogues.

Chapter 5

(1) See Figure 5.1(b), Figure 5.3(a) and Figure 5.3(c).

(2) (a) See Section 5.2. (b) See Equation (5.1) in section 5.2.

(c)Ecoulombic¼

QC 1 QC 2

DrC 1  2

þ

(QC 1 QCH)

DrC 1 H

þ 3

(QC 2 QCH)

DrC 2 H

whereQrepresents the point charge on the specified atoms andrthe distance

between the specified atoms.

264 ANSWERS TO QUESTIONS