Biomedical Engineering Reference
In-Depth Information
H
N
R
6
R
3
S
N
R
7
O
O
9
pIC
50
pancreas
ð
Þ ¼
6
:
455
1
:
254
ð
0
:
28
Þ
C
log
P
R
ðÞ
2
:
184
ð
0
:
86
Þ
Vw R
ðÞ
þ
0
:
454
ð
0
:
14
Þ
I
3
þ
0
:
505
ð
0
:
16
Þ
I
6
Q
2
n
¼
23
;
r
¼
0
:
920
;
¼
0
:
765
;
s
¼
0
:
223
;
F
¼
24
:
66
:
ð
13
Þ
pEC
50
rat aorta
ð
Þ ¼
3
:
772
þ
0
:
837
ð
0
:
37
Þp
6
þ
1
:
443
ð
0
:
35
Þp
7
(14)
Q
2
n
¼
20
;
r
¼
0
:
900
;
¼
0
:
737
;
s
¼
0
:
307
;
F
¼
36
:
27
:
Equation (13) suggested that the R
3
-andR
7
-substituents may face the steric
problem. Thus, it suggested that the bulky substituents, which also affect the hydro-
phobicity, may not be advantageous for the activity. However, the positive coeffi-
cients of the indicator variables
I
3
and
I
6
, where the former is for an aminoisopropyl
substituent at the 3-position and the latter for a chloro substituent at the 6-position,
indicate that such substituent would be beneficial to the pancreatic activity of the
compounds. The myorelaxant effect on rat aorta rings (EC
50
) of the compounds was
shown to be positively correlated with hydrophobic constants of R
6
and R
7
sub-
stituents (14) signifying the importance of hydrophobic property of these substituents
in modulating the activity of the compounds. These equations suggest the sub-
structural requirement in this class of compounds for K
ATP
channel modulation.
In a further study, Sharma et al. enlarged the scope of preceding QSAR model
for myorelaxant effects [
56
] by including more benzothiadiazine-dioxide
derivatives [
54
,
55
] in the analysis. The enlarged QSAR of all the compounds
was reinvestigated in CP-MLR with topological descriptors from DRAGON soft-
ware. The following equation was found to be the best model for the myorelaxant
activity of the compounds [
57
].
pEC
50
rat aorta
ð
Þ ¼
3
:
927
1
:
581 0
ð
:
342
Þ
Mor24u
þ
0
:
875 0
ð
:
126
Þ
Mor04m
0
:
387 0
:
096
ð
Þ
Mor10m
þ
0
:
843 0
:
216
ð
Þ
Mor13e
(15)
þ
2
:
159 0
ð
:
688
Þ
G3u
þ
0
:
151 0
ð
:
018
Þ
L1m
Q
2
n
¼
;
r
¼
:
;
¼
:
;
s
¼
:
;
F
¼
:
:
57
0
844
0
628
0
428
20
69
The descriptors emerged in above model Mor24u, Mor04m, Mor10m and
Mor13e belong to 3D MoRSE (3D molecule representation of structures based on
electron diffraction) class. These descriptors are based on the idea of obtaining
information from the 3D atomic coordinates by the transformations used in electron
diffraction studies for preparing theoretical scattering curves. These descriptors in
