Biomedical Engineering Reference
In-Depth Information
N
R
1
N
O
Cl
N
O
O
H
X
HN
O
N
R
2
R
3
N
H
9.25
9.26
(CH
2
)n
N
N
Cl
N
O
N
O
O
HN
O
O
C
H
N
N
H
CH
3
9.27
9.28
O
O
O
N
O
S
Cl
O
N
O
S
N
N
I
9.29
9.30
9.31
O
O
Figure 9.4
KLK7 inhibitors. In the general formula R
1
¼
H, CN, (C
1-8
)alkyl, (C
2-8
)
alkenyl, (C
2-8
)alkynyl, halogen, (C
1-8
)alkylamino, (C
1-8
)alkylamino(C
1-8
)
alkyl, (C
1-8
)alkoxy, halo(C
1-8
)alkyl, R
2
¼
(C
1-8
)alkyl, (C
1-8
)alkylamino,
(C
1-8
)alkylamino(C
1-8
)alkyl, di(C
1-8
)alkylamino(C
1-8
)alkyl, halo(C
1-8
)
alkyl, (C
1-8
)alkoxy, (C
1-8
)alkoxy(C
1-8
)alkyl or (CH
2
)
m
-Z where m
¼
1, 2
or 3 and Z
¼
unsubstituted or substituted (C
3-8
)cycloalkyl, (C
6-18
)aryl
or heterocyclic having five- to six-ring members and one to four het-
eroatoms from N, O, and S. R
3
¼
H, (C
1-8
)alkyl, (C
1-8
)alkoxy, (C
6-18
)aryl
or heterocyclic having five- to six-ring members and one to four
heteroatoms from N, O, and S, n
¼
1, 2 or 3, X
¼
(CH
¼
CH), -NH-,
(N
¼
CH), O or S.
SmithKline AB), while it improved skin morphology without the side effects of
betamethasone.
120
9.4.5 General Modulators of KLKs
Cardiac glycosides were identified by HTS as novel transcriptional regulators
of KLKs that could be exploited therapeutically, as they affect KLK activities,
although they do not directly inhibit KLK enzymatic activity.
121
Modulation of
KLK transcription is also conferred by epigenetic drugs,
122
vitamin D
3
ana-
logs,
122,123
9-cis and 13-cis retinoic acid,
124
and steroid hormones.
7,16
However,
these classes of compounds do not act specifically on KLK genes but act on a wide
range of other genes. Azelaic acid (nonanedioic acid, product of ozonolysis of
oleic acid) reduces KLK5 expression in skin with significant implications for the
