Synthesis and Anticancer Activity of N-Aryl-5-substituted-1,3,4-oxadiazol-2-amine Analogues
Table 1
Pharmacokinetic parameters important for good oral bioavailability of N-aryl-5-substituted-1,3,4-oxadiazol-2-amine analogues (4a–x).
Compound
R
R1
%ABS
Volume ()
TPSA ()
NROTB
HBA
HBD
c
MW
Lipinski’s violation
Rule
—
—
—
—
—
≤10
<10
<5
≤5
<500
≤1
4a
4-Methyl-
4-Methoxy-
88.23
254.625
60.18
4
5
1
3.66
281
0
4b
4-Methyl-
4-Chloro-
91.42
242.615
50.95
3
4
1
4.33
285
0
4c
4-Methyl-
4-Hydroxy-
84.44
237.097
71.18
3
5
2
3.38
267
0
4d
4-Methyl-
3,4-Dimethoxy-
85.05
280.171
69.41
5
6
1
3.59
311
0
4e
4-Methyl-
—
86.89
210.647
64.09
3
5
1
2.95
241
0
4f
4-Methyl-
—
91.42
210.647
50.95
3
4
1
2.73
203
0
4g
4-Bromo-
4-Methoxy-
88.23
255.949
60.18
4
5
1
4.04
345
0
4h
4-Bromo-
4-Chloro-
91.42
243.939
50.95
3
4
1
4.72
349
0
4i
4-Bromo-
4-Hydroxy-
84.44
238.421
71.18
3
5
2
3.76
331
0
4j
4-Bromo-
3,4-Dimethoxy-
85.05
281.495
69.41
5
6
1
3.97
375
0
4k
4-Bromo-
—
86.89
211.972
64.09
3
5
1
3.34
305
0
4l
4-Bromo-
—
91.42
192.358
50.95
3
4
1
3.12
267
0
4m
4-Chloro-
4-Methoxy-
88.23
251.6
60.18
4
5
1
3.92
301
0
4n
4-Chloro-
4-Fluoro-
91.42
230.985
50.95
3
4
1
4.09
289
0
4o
4-Chloro-
4-Chloro-
91.42
239.59
50.95
3
4
1
4.60
305
0
4p
4-Chloro-
4-Hydroxy-
84.44
234.072
71.18
3
5
2
3.64
287
0
4q
4-Chloro-
3,4-Dimethoxy-
85.05
277.145
69.41
5
6
1
3.85
331
0
4r
4-Chloro-
—
86.89
207.622
64.09
3
5
1
3.22
261
0
4s
2,4-Dimethyl-
4-Methoxy-
88.23
271.186
60.18
4
5
1
4.00
295
0
4t
2,4-Dimethyl-
4-Fluoro-
91.42
271.186
50.95
3
4
1
4.17
283
0
4u
2,4-Dimethyl-
4-Chloro-
91.42
259.176
50.95
3
4
1
4.68
299
0
4v
2,4-Dimethyl-
4-Hydroxy-
84.44
253.658
71.18
3
5
2
3.73
281
0
4w
2,4-Dimethyl-
3,4-Dimethoxy
85.05
296.732
69.41
5
6
1
3.93
325
0
4x
2,4-Dimethyl-
—
86.89
207.622
64.09
3
5
1
3.30
255
0
%ABS: percentage of absorption; TPSA: topological polar surface area; NROTB: number of rotatable bonds; MW: molecular weight; Log P: logarithm of compound partition coefficient between n-octanol and water; HBD: number of hydrogen bond donors; HBA: number of hydrogen bond acceptors.