Page 154 - Medicinal Chemistry Self Assessment

Section 4 Whole Molecule Drug Evaluation

Answers

2.10 Cefprozil

Cefprozil is a second-generation cephalosporin that exhibits good Gram (+) activity with improved Gram (–) activity
Medicinal Chemistry Self-Assessment Book: Batch Two
as compared to the first-generation cephalosporins. Effective against the majority of bacteria that cause upper and
Chapters 1.10 and 2.10
lower respiratory infections, as well as skin infections, cefprozil was a first-line anti-infective agent until an increase in

Chapter 1.10/2.10 (remove bold from drug name)
the incidence of resistance and the development of newer agents decreased its “favored” status.

Cefprozil (Cefzil)

1. Conduct a complete structural evaluation of cefprozil and use the information in the grid to inform your
Chpater 1.10/2.10 Corrected structure (product of E transformation)
answers to the questions that follow.

Answer NH 2 H
H O N H H S
Function
O N
H O O Amino Acids
CH
3
O H
H H CO 2 H That Can
N S Interact with
NH
Function Functional 2
O
Character N OH
H O O CH 3 Interaction(s) Group via
Character Acidic, Basic, Function Possible with H-Bonding (at H N H H S
O
CO 2 H
Name of Hydrophilic or Neutral ↑ Solubility Biological Target H O pH=7.4) 2
Functional and/or Provide pK and/or at Physiological None Is O N CH
B
a
A
Group Hydrophobic When Relevant ↑ Absorption pH=7.4 Acceptable 3
CO 2 H
C
A Phenol Hydrophilic (OH) Acidic Solubility (OH) OH: Ser, Tyr, Trp, His,
H
Hydrophobic (Ar) (pK 9–10) Absorption (Ar) NH 2 H-bonding (A+D) Thr, Cys, Asn, Gln
a H H
N
Dipole–dipole S
Ion–dipole (as the
O
N
H O dipole) CH 3
O
Ar: CO 2 H
van der Waals
NH 2 H F Hydrophobic D
N H H S π-π Stacking
E
O N
H O O CH 3 NH 2 H
O 143 N H O N H H S
O S O N
-O O O CH 3
OH O
CO 2 H
NH 2 H H H
N S
O N OH
H O O
CO 2 H