Chemistry Reference
In-Depth Information
R
1
Y
N
R
2
X
N
H
N
H
N
H
brimamide (
54
): R
1
= H, R
2
= Me, X = CH
2
, Y = S
methiamide (
55
): R
1
= Me, R
2
= H, X = Y = S
cimetidine (
57
): R
1
= R
2
=Me, X = S, Y = NCN
H
2
N
N
N
NH
N
H
2
N
S
S
NH
2
N
H
NH
2
N
H
N
SO
2
NH
2
guanidinohistamine (
56
)
famotidine (
58
)
Figure 10.13
Structures of H
2
-blockers
10.4.3
Imipenem
Imipenem (59) is one of the carbapenem, which possess a broad spectrum of antimicrobial
activity against Gram positive as well as Gram negative bacteria, such as Pseudomonas
aeruginosa [94]. This compound was transformed from thienamycin (60) (Figure 10.14)
produced by Streptomyces cattleya. This antibiotic was known to be rather unstable, for
example, less stable than benzylpenicilline at pH 7. Low stability of 60 was also found when
the concentration was high, which was deduced from the intermolecular aminolysis of the
azeitidinone by the cysteamine side chain in 60, however, basic functionality at the terminal
of carbon chain was found to be necessary because the corresponding N-acetyl derivative
has lost the activity. Thus, the conversion of the amino group to a more basic one would
result in a compound with increased stability by protonation of the basic group in
physiological conditions. As expected, 59 with a formylimidoyl group was 5-30 times
more stable compared with 60 but kept the same or similar antimicrobial activity [95].
OH
H
S
R
N
H
O
CO
2
H
imipenem (
59
): R = CH=NH
thienamycin (
60
): R = H
Figure 10.14
Structures of imipenem (59) and thienamycin (60)
