Biomedical Engineering Reference
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the development of the first nonpeptidic sstr5 antagonist [354]. The
screening of an imidazolyl library led to a tetrahydro-b-carboline analo-
gue antagonist that was selective for the sstr3 receptor subtype [355].
NH
NH
O
O
N
N
N
H
NH
2
N
H
NH
2
O
O
NH
O
N
O
N
H
HN
O
sstr2-5
sstr5
Ph
Br
F
O
N
Cl
HN
H
N
N
N
N
Cl
NH
O
Cl
S
O
H
2
N
NNC-26-9100
sstr4
sstr5
H
2
N
NH
N
S
N
N
N
O
sstr2/3
Figure 3.47 Somatostatin mimetic agonists
Seebach used the propensity of b
2
/b
3
-dipeptide and g-dipeptide combi-
nations to adopt turn structures and to develop derivatives with nanomolar
affinity and selectivity for some of the hsstrs [356-358] (Figure 3.49).
The observation that some of the glucose-based somatotatin mimetics
(Figure 3.50) also showed affinity for the NK1 receptor [335,336] led the
Hirschman group to develop a cyclic hexapeptide NK1 antagonist, based
on the somatostatin scaffold [359], which is entirely different from the
approach that led to nonpeptide NK1 antagonists [327]. A similar cyclic
b-turn scaffold is also present in an NK2 antagonist [360].
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