Chemistry Reference
In-Depth Information
OSO
3
-
O
MeO
MeO
CO
2
-
OSO
3
-
MeO
O
MeO
O
O
-
O
3
SO
-
O
3
SO
-
O
2
C
H
H
OSO
3
-
O
MeO
O
-
O
3
SO
-
O
3
SO
O
O
MeO
OMe
84
OMe
OSO
3
-
O
Me
MeO
CO
2
-
OSO
3
-
MeO
O
O
MeO
O
O
-
O
3
SO
-
O
3
SO
OSO
3
-
-
O
2
C
O
MeO
O
O
-
O
3
SO
-
O
3
SO
O
MeO
O
OMe
85
OMe
OSO
3
-
O
OSO
3
-
Me
MeO
O
O
-
O
3
SO
-
O
3
SO
CO
2
-
OSO
3
-
MeO
O
O
MeO
O
-
O
2
C
O
-
O
3
SO
-
O
3
SO
O
OMe
MeO
O
OMe
86
OSO
3
-
O
Me
MeO
CO
2
-
OSO
3
-
MeO
O
MeO
O
O
-
O
3
SO
-
OMe
OSO
3
-
O
3
SO
O
OMe
O
O
O
-
O
3
SO
-
O
3
SO
MeO
87
-
OMe
O
2
C
OMe
Fig. 24 Structures of the four synthetic pentasaccharides 84-87.
R
1
R
2
O
HO
HO
OH
OH
88
R
1
= Cl, R
2
= OEt, IC
50
(h-SGLT1) = 1960 nM
IC
50
(h-SGLT2) = 0.88 nM
in vitro micronucleus negative
Fig. 25 Dioxa-bicyclo[3.2.1]octane-based SGLT2 inhibitor 88.
and alarming statistics forced the scientific community to discover new
targets.
114
Recently, sodium glucose co-transporter 2 (SGLT2) inhibition
has emerged as a very promising approach for the treatment of type 2
diabetes.
115
SGLT2 is a protein in humans that facilitates glucose re-
absorption in the kidney. Inhibition of SGLT2 leads to the decrease in
blood glucose due to the increase in renal glucose excretion. Since 2010,
Mascitti and co-workers investigated some research in the synthesis of a
new class of SGLT2 inhibitors bearing a unique dioxa-bicylco[3.2.1]-
octane motif (Fig. 25).
116
The compound 88 appeared to be one of the most potent and selective
SGLT2 inhibitors from this class and has demonstrated robust eciency
in preclinical rodent models. The key of this inhibition is related to the
formation of the dioxa-bicyclo[3.2.1]octane motif with full control of
stereochemistry.
3.6 Lytic transglycosylases
Bacterial cell wall recycling commences by degradation of the pepti-
doglycan, the major constituent of the cell wall, by the family of lytic
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