MChem Master of Chemistry Master of Chemistry: Pharmaceutical Chemistry 4

Question 1

Which strategy is used to overcome rapid metabolism of a drug by deuterium incorporation?

Accepted Answer

Deuterium isotope effect slows C–H bond cleavage at metabolic sites

Answer

Replacing metabolically vulnerable C–H bonds with C–D bonds exploits the primary kinetic isotope effect, slowing oxidative metabolism at those sites.

Question 2

What is the primary goal of bioisosteric replacement in drug optimization?

Accepted Answer

Maintain biological activity while modifying physicochemical properties

Answer

Bioisosteric replacement substitutes one functional group with a similarly shaped/polar group to retain target affinity while improving ADMET properties or patentability.

Question 3

Which ICH guideline specifically addresses impurity thresholds and qualification requirements for drug substances?

Accepted Answer

ICH Q3A

Answer

ICH Q3A (Impurities in New Drug Substances) defines reporting, identification, and qualification thresholds for chemical impurities in APIs.

Question 4

In fragment-based drug discovery (FBDD), what molecular weight range typically defines a fragment?

Accepted Answer

100–250 Da

Answer

Fragments are typically 100–250 Da (rule of three: MW ≤300, H-bond donors ≤3, cLogP ≤3), allowing efficient exploration of chemical space with weak but ligand-efficient binders.

Question 5

Which mechanism of resistance to β-lactam antibiotics is most clinically significant?

Accepted Answer

Production of β-lactamase enzymes

Answer

β-Lactamase production is the predominant resistance mechanism; these enzymes hydrolyze the β-lactam ring, rendering the antibiotic inactive.

MChem Master of Chemistry Practice Test

MChem Master of Chemistry Practice Test

MChem Master of Chemistry Master of Chemistry: Pharmaceutical Chemistry 4