225
the spiroquinazolines was found to be important for the activity: all the active molecules had low EP(N1) and EP(N1) < EP(N3).
Thus, the electron density distribution in the molecules and steric factors are
equally important for binding the molecules to the receptor. This computational
study should aid in design of new molecules in this class with improved PDE7
inhibition.
7.2.12 HIV-1 Transcriptase
Searching for new effective anti-AIDS drug remains the challenge for drug chemistry [85]. One of the prospective ways is the development of efficient inhibitors of
7 Density Functional Theory Calculations of Enzyme–Inhibitor …
1
+
1+
2
2
+ &
&O
1
+
1+
2
&O
1
2
1
+
1+
2
2
&+
73
74
75
EP(N1)
30.84;
42.81
28.93
EP(N3)
38.50
36.73
38.25
pIC 50
7.85
5.02
7.42
1
+
1+
2
&O
1
+
1+
2
&O
1
+
1+
2
76
77
78
EP(N1)
50.12
30.85
42.54
EP(N3)
38.45
38.22
36.53
pIC 50
5.32
6.77
5.18
Fig. 7.7  Structural formula, electrostatic potential values on N1 and N3 atoms (EP(N1) and
EP(N3), respectively) and activity in molar concentration (pIC 50 ) for structures 73–78