Receptor Guided 3D-QSAR: A Useful Approach for Designing of IGF-1R Inhibitors

Table 1

The structures and observed IGF inhibitory activities [15].

No.	Structure	R	IC50 (M)	pIC50
1	A	4-OBn	1.97×10^−6	5.706
2	A	3-OH	0.518×10^−6	6.286
3	A	3-OBn–4-OMe	1.35×10^−6	5.870
4	A	3-OBn–4-OH	3.31×10^−6	5.480
5^*	B	Cyclopentyl	3.5×10^−6	5.456
6	B	Cyclohexyl	1.05×10^−6	5.979
7^*	B	–CH2–cyclopropyl	2.27×10^−6	5.644
8^*	B	–CH2–cyclohexyl	1.11×10^−6	5.955
9	B	–CH2CH2OMe	6.28×10^−6	5.202
10	B	–CH2–2-pyridyl	1.09×10^−6	5.963
11	C	H	0.606×10^−6	6.218
12	C	2-F	0.224×10^−6	6.650
13	C	3-F	0.51×10^−6	6.292
14	C	4-F	1.23×10^−6	5.910
15	C	2-Cl	0.343×10^−6	6.465
16	C	3-Cl	2.12×10^−6	5.674
17^*	C	4-Cl	0.980 ×10^−6	6.009
18	C	2-OCF2H	3.28 ×10^−6	5.484
19	C	3-OCF2H	5.78 ×10^−6	5.238
20	C	4-OCF2H	2.82 ×10^−6	5.550
21	C	2,3-Difluoro	0.898 ×10^−6	6.047
22	C	3,4-Difluoro	4.48 ×10^−6	5.349
23^*	C	2,5-Difluoro	0.329 ×10^−6	6.483
24	C	2,6-Difluoro	0.215 ×10^−6	6.668
25	C	3,5-Difluoro	1.35 ×10^−6	5.870
26	C	2,6-Dichloro	1.67 ×10^−6	5.777
27	C	2-Cl,6-F	0.248 ×10^−6	6.606
28	D	Cyclopentyl	1.05 ×10^−6	5.979
29	D	Cyclohexyl	3.51 ×10^−6	5.455
30	D	Cycloheptyl	3.79 ×10^−6	5.421
31^*	D	Phenyl	1.68 ×10^−6	5.775
32	E	trans-NH2	0.221 ×10^−6	6.656
33	E	cis-NH2	0.775 ×10^−6	6.111
34^*	E	trans-NHMe	0.105 ×10^−6	6.979
35	E	trans-Pyrrolodinyl	1.82 ×10^−6	5.740
36^*	E	trans-Piperidinyl	3.40 ×10^−6	5.469
37	E	trans-NHPh	1.30 ×10^−6	5.886
38	E	trans-NHBn	1.39 ×10^−6	5.857
39	F	trans-NH2	0.119 ×10^−6	6.924
40	F	cis-NH2	0.228 ×10^−6	6.642
41	F	trans-N(Et)2	0.115 ×10^−6	6.939
42	F	trans-Azetidinyl	0.081 ×10^−6	7.092
43	F	trans-Pyrrolidinyl	0.103 ×10^−6	6.987
44^*	F	trans-Morpholino	0.091 ×10^−6	7.041
45^*	G	trans-Pyrrolidinyl	0.116 ×10^−6	6.936
46	G	cis-Pyrrolidinyl	0.089 ×10^−6	7.051
47	G	cis-NH2	0.060 ×10^−6	7.222
48	G	cis-NMe2	0.166 ×10^−6	6.780
49^*	G	cis-Piperidinyl	0.237 ×10^−6	6.625
50	G	cis-Morpholino	0.148 ×10^−6	6.830
51	G	cis-NH-iPr	0.220 ×10^−6	6.658
52	G	cis-N(Me)-Piperizinyl	0.265 ×10^−6	6.577
53	H	trans-NH2	0.526 ×10^−6	6.279
54	H	cis-NH2	0.554 ×10^−6	6.256

^* Compounds used in the test set.