483
14 Quantitative Structure-Property Relationship Analysis …
Fragment
ΔP
ΔC S
1
2
3
Linker
–C 2 H 4 –,
− 0.003
− 0.016
–C 3 H 6 –
0.003
− 0.033
–C 4 H 8 –
− 0.014
− 0.081
–C 5 H 10 –
− 0.006
− 0.197
–CH = CH–
− 0.005
− 0.109
Functional group
–COOH
− 0.126
− 0.011
–CONH 2
− 0.181
0.252
–NH 2
− 0.103
0.059
–CONH–
− 0.044
− 0.009
–N(CH 3 ) 2
− 0.024
− 0.016
–OH
− 0.032
0.03
–OCH 3
− 0.018
0.006
–NO 2
0.000
− 0.017
–COOC 2 H 5
− 0.022
0.053
Terminal fragment
–F
− 0.008
− 0.005
–Cl
0.003
− 0.002
–I
0.0
− 0.115
–CF 3
−0.046
− 0.048
–CH 3
− 0.011
− 0.004
–C 2 H 5
0.0
− 0.032
–C 3 H 7
− 0.004
0.0
–iPr
− 0.05
0.005
–NH–iPr
− 0.282
0.049
–NH–tBu
− 0.737
0.049
Saturated cycle
Cyclohexane
− 0.022
− 0.074
Cyclopentane
0.0
− 0.063
Piperidine
− 0.083
− 0.001
Tetrahydrofuran
− 0.187
− 0.016
Piperazine
− 0.035
− 0.027
Pyrrolidine
− 0.156
0.0
Unsaturated cycle
Phenyl
− 0.007
− 0.089
Pyridine
− 0.038
− 0.152
Pyrazine
− 0.134
− 0.048
Pyrimidine
− 0.15
− 0.148
Cyclohexene
− 0.023
− 0.125
1H-imidazole
− 0.102
− 0.017
Table 14.5  Relative effect
of some fragments on the
change of the penetration
coefficient (ΔP) and solubility (ΔC S ) for active pharmaceutical ingredient in an
aqueous medium