Page 198 - Medicinal Chemistry Self Assessment
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2.18 Levothyroxine (T ) 187
4
Answer
• Evaluation of the dehalogenation transformation that leads to metabolite A: The outer ring of
levothyroxine is dehalogenated to produce metabolite A. This metabolite retains the two inner
ring iodo substituents; therefore, the shape of the hormone remains perpendicular. This metabo-
lite retains its biological activity.
• Evaluation of the dehalogenation transformation that leads to metabolite B: The inner ring of
levothyroxine is dehalogenated to produce metabolite B. This metabolite retains only one inner
ring iodo substituent; therefore, the shape of the hormone cannot remain perpendicular. Because
the phenol is not positioned appropriately to participate in an important binding interaction
with the thyroid hormone receptor, this metabolite is inactive.
