Page 194 - Medicinal Chemistry Self Assessment

1.17 and 2.17 – remove bold from label

E

C
F
B

Section 4 Whole Molecule Drug Evaluation
D
A
Answers
Hydrocortisone

Question #3 structure needs to be replaced:
2.18 Levothyroxine (T )
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21
17
Levothyroxine (T ) is a naturally produced thyroid pro-hormone. In its active form, tri-iodo-L-thyronine (T ) is
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3
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responsible for regulating oxygen consumption and calorigenesis (think metabolism, metabolic rate, and thermogen-
esis). T is biosynthesized and stored in thyroglobulin molecules until it is needed. Once proteolyzed from thyroglob-
A
4
ulin and transported to the desired target tissue, T undergoes dehalogenation catalyzed by thyroxine dehalogenase to
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the active thyroid hormone T .
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1.18 and 2.18 – remove bold from label
1. Conduct a structural evaluation of levothyroxine (T ), focusing on the boxed functional groups, and use

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the information in the grid to inform your answers to the questions that follow.

E
A I C D O
H O I
OH
NH
I O 2
B I

L-Thyroxine

Answer

Function

Character Function Amino Acids That
Acidic, Basic, Can Interact with the
Functional Group via
Character or Neutral Function Interaction(s)
Possible with Hydrogen Bonding
Name of Hydrophilic Provide ↑ Solubility Biological Target Interactions at
Functional and/or pK When and/or at Physiological pH=7.4
a
Group Hydrophobic Relevant ↑ Absorption pH=7.4 None Is Acceptable
A Phenol Hydrophilic (OH) Acidic Solubility (OH) H-bonding (A+D) Ser, Thr, Tyr, Cys, Asn, Gln,
Hydrophobic (Ar) pK =9–10 Absorption (Ar) Dipole–dipole Trp, His
a
Ion–dipole (as the
dipole)
B Ether Hydrophilic (O) Neutral Solubility (O) H-bonding (A) Ser, Thr, Tyr, Cys, Asn, Gln,
Hydrophobic (R) Absorption (R) Dipole–dipole His, Trp
Ion–dipole (as the
dipole)

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