Page 71 - Medicinal Chemistry Self Assessment
P. 71
60 Medicinal Chemistry Self Assessment
4. The synthetic soluble ester is present. formation has an effect on overall drug water solubility.
4. The synthetic glucocorticoids are often esterified at C-21 to produce prodrugs. Both lipophilic and
water soluble esters can be formed. Evaluate each of the four prodrugs drawn below and determine
whether a lipophilic or water soluble ester is present. Determine how prodrug formation has an
effect on overall drug water solubility.
A B
C D
Type of Ester Formed Effect on Overall Drug Water Solubility
A
B
C
D
a. Provide a structural rationale for why prodrugs (e.g., B and D) are used in the preparation of
aqueous injectable products to be administered intramuscularly (IM) or intravenously (IV).
b. Provide a structural rationale for why prodrugs (e.g., A and C) are used in the preparation of
depot injections.
5. Lipophilic glucocorticoid esters typically do not concentrate in the urine, but rather undergo glomerular
filtration followed by tubular reabsorption. Provide a brief rationale for why lipophilic glucocorticoid
esters do not concentrate in the urine and determine what effect this has on duration of drug action.
6. Which type of prodrug, water soluble ester salts, or lipophilic esters, would you anticipate to have
greater systemic side effects?
