Biomedical Engineering Reference
In-Depth Information
1
v
Y
1
v
Y
2
ð
=
Þ¼
:
ð
:
Þ þ
:
ð
:
Þ
w
:
ð
:
Þð
w
Þ
log 1
IC
50
0
064
4
211
3
524
2
652
0
486
0
398
1
v
X
þ
0
:
485
ð
0
:
428
Þ
w
1
:
710
ð
0
:
672
Þ
I
1
þ
0
:
927
ð
0
:
531
Þ
I
R
1
Q
2
v
n
¼
23
;
r
¼
0
:
913
;
¼
0
:
58
;
s
¼
0
:
46
;
F
¼
17
:
03
; ð
w
Y
Þ
opt
¼
3
:
63
(1)
In (1), the
I
1
and
I
R
are indicator variables. The
I
1
has been used to account for
the amine character of Y-substituents (
I
1
¼
1) and zero otherwise. The
I
R
takes a
value of 1 for R-configuration and zero for any other configuration (S or RS). In the
equation, the negative coefficient of
I
1
suggests that a Y-substituent with amine
character is not favorable for the activity. The positive effect of
I
R
suggests that
R-configuration is favorable for the activity. Also, the equation suggests that 3.36
is the optimum value for the first-order valence molecular connectivity index of
Y
1
v
. The first-order valence molecular connectivity index of X (
1
v
ð
w
Y
Þ
w
X
) is linearly
and positively correlated with the activity. In these compounds
1
v
and calculated
w
log
P
are highly correlated (
r
0.73). In view of this, it is suggested that
I
Ks
blocking activity of the benzodiazepine derivatives may be influencing through
the hydrophobic character of the molecules [
33
].
¼
2.2 Benzopyrans
Cromakalim is a potential potassium channel-opener (PCO). It is a compound of
benzopyran (chromane) class. It has marked myorelaxant activity resulting from the
smooth muscle K
ATP
channels [
34
]. It activates K
ATP
channels [
35
,
36
] and thereby
causes plasma membrane hyperpolarization and reduction in cell excitability. The
active isomer is levcromakalim (2). The pharmacological profile of cromakalim
attracted the attention of several groups to discover other chemotypes as potential
potassium channel-openers. Cromakalim being a benzopyran class of compound,
benzopyran scaffold has gained considerable attention in the modulation of potas-
sium channels activity.
O
N
NC
OH
O
2
2.2.1
6-Substituted Benzopyrans
In one of the early modeling studies, Mannhold and coworkers have investigated
the 6-substituted benzopyrans (3) as potassium channel activators [
37
]. These
