Fundamentals of Medicinal Chemistry

Table 3.1 Examples of the acids and bases used to form the salts of drugs

Anions and anion sources Cations and cation sources

Ethanoic acid – ethanoate (CH 3 COO) Sodium – sodium ion (Naþ)

Citric acid – citrate (see Figure 3.5) Calcium – calcium ion (Ca^2 þ)

Lactic acid – lactate (see Figure 3.5) Zinc – zinc ion (Zn^2 þ)

Tartaric acid – tartrate (see Figure 3.5) Diethanolamine – R 2 NH 2 þ(see Figure 3.5)

Hydrochloric acid – chloride (Cl) N-Methylglucamine – RNH 2 þCH 3 (see Figure 3.5)

Sulphuric acid – sulphate (SO 42 ) 2-Aminoethanol (HN 2 CH 2 CH 2 OH) – RNH 3 þ

Sulphuric acid – hydrogen sulphate (HSO 4 )

H

OCH 2 CH 2

OCH 2 CH 2

N

H

H

H

C

C

O

O

O

O

O

H

C H

H

C H

H C H

H

CH 3

H

C

O

O O H

H

C

Lactic acid.

H

C

N

O H

H

H O C

O H

C

C

CH 2

CH 2

CH 3

O H

O

H

H

H

H

H

C

C

O

O

O

O

O

H

C H

H

H O C H

Citric acid.

Tartaric acid.

Diethanolamine

(diolamine)

N-methylglucamine

(meglumine)

Figure 3.5 Examples of the structures of acids and bases whose structures contain water solubiliz-

ing groups. The possible positions of hydrogen bonds are shown by the dashed lines------; lone pairs

are omitted for clarity. At room temperature itis highly unlikely that all the possible hydrogen bonds

will be formed.Note:hydrogen bonds are not shown for the acidic protons of the acids as these

protons are donated to the base on salt formation. Similarly, no hydrogen bonds are shown for the

lone pairs of the amino groups, because these lone pairs accept a proton in salt formation

presence of a high concentration of chloride ions in the stomach will reduce the

solubility of sparingly soluble chloride salts because of the common ion effect.

3.6 The incorporation of water solubilizing groups in a structure

The discussion of the introduction of water solubilizing groups into the structure

of a lead compound can be conveniently broken down into four general areas:

THE INCORPORATION OF WATER SOLUBILIZING GROUPS IN A STRUCTURE 65