Page 122 - Medicinal Chemistry Self Assessment

modulating a biochemical pathway. In either case, the drug has to get to its biological target. Using your
knowledge about functional group character, describe how both of the drugs get to their respective
biological targets. Consider the concepts of solubility, absorption, distribution, and route of administration
in your answer. [pH (stomach) = 1; pH (intestine) = 8; pH (plasma) = 7.4]
2. Each of these drug molecules will treat a particular ailment by either managing a symptom or
Cl NCH 3
OH
O
O
N CH 2 OH 2.4 Salts and Solubility 111
O
CONH 2
3. Based on your structural evaluation, provide a rationale for why each of these drugs cannot be deliv-
Scopolamine
ered via an oral route of administration, or why there is limited absorption of the drug when it is
Loperamide
administered orally.
Insulin Structure
3. Based on your structural evaluation, provide S a rationale for why each of these drugs cannot be A Chain
S
H 2 N
ValGlu GlnCys CysThr SerIle CysSer LeuTyr GlnLeu GluAsn TyrCys Asn COOH
Ile
Gly
delivered via an oral route of administration, or why there is limited absorption of the drug when it is
S S
administered orally. S S B chain
H 2 NPhe ValAsn GlnHis LeuCys GlySer His Leu ValGlu AlaLeu Tyr Leu ValCys GlyGlu Arg
Gly
HOOC Thr 30 Lys 29 Pro 28 Thr 27 Tyr Phe Phe

PO 3 Na 2
H 2 N PO 3 Na 2
OH

Alendronate

Insulin Answer
Insulin is a molecule composed of two peptide subunits connected to one another via two disulfide
linkages. Peptide bonds do not survive the hydrolytic environment found in the stomach. Insulin can
undergo acid catalyzed hydrolysis in the aqueous environment of the stomach, as well as enzymati-
cally catalyzed hydrolysis in the same physiological compartment. Because of this rapid degradation,
peptide-based drugs like insulin cannot be delivered via the oral route.

Alendronate contains two ionizable phosphonates, an ionizable primary amine, and a tertiary
alcohol. These functional groups impart significant hydrophilic character and make alendronate very
water soluble. There is very, very, little hydrophobic character to contribute to absorption across the
GI mucosal membranes. Although alendronate can be administered orally, less than 6% of a given
dose is absorbed and distributed systemically.
4. Based on your structural evaluation of embeconazole, answer the following questions:

4. Based on your structural evaluation of embeconazole, answer the following questions:

Embeconazole