Compound,SMILES,MOR Ki (nM),DOR Ki (nM),KOR Ki (nM),NTS1 Ki (nM),NTS2 Ki (nM)
,,,,,,
1,OC([C@@H](NC([C@H](C(C)(C)C)NC([C@H](CC1=CC=C(O)C=C1)NC([C@H](CCC2)N2C([C@H](CCCNC(N)=N)NC([C@H](CCCNC(N)=N)N)=O)=O)=O)=O)=O)CC(C)C)=O,,,,3.6 ± 0.4,0.46 ± 0.03
2,O=C([C@H](CCCCN)NC(C[C@H](CCCCN)N)=O)N1[C@@H](CCC1)C(N2CC3=C(C=C(O)C=C3)C[C@H]2C(N[C@@H](C(C)(C)C)C(N[C@@H](CC(C)C)C(O)=O)=O)=O)=O,,,,3790 ± 1300,2.86 ± 1.3
3,OC([C@H](CC(C)C)NC([C@H](C(C)(C)C)NC([C@@H](NC([C@@H]1CCCN1C([C@H](CCCNC(N)=N)NC([C@H](CCCNC(N)=N)NC(CCN2C([C@@H](NC([C@@H](CCCNC(N)=N)NC([C@@H](N)CC3=C(C)C=C(O)C=C3C)=O)=O)CC4=C(C=CC=C4)C2)=O)=O)=O)=O)=O)CC(C=C5)=CC=C5O)=O)=O)=O,1.32 ± 0.45,56.4 ± 4.5,78.6 ± 20,0.43 ± 0.07,0.09 ± 0.07
4,OC([C@H](CC(C)C)NC([C@H](C(C)(C)C)NC([C@@H](NC([C@@H]1CCCN1C([C@H](CCCCN)NC([C@H](CCCCN)NC(CCN2C([C@@H](NC([C@@H](CCCNC(N)=N)NC([C@@H](N)CC3=C(C)C=C(O)C=C3C)=O)=O)CC4=C(C=CC=C4)C2)=O)=O)=O)=O)=O)CC(C=C5)=CC=C5O)=O)=O)=O,4.89 ± 0.30,213 ± 44,201 ± 80,2.3 ± 0.4,0.29 ± 0.2
5,OC([C@H](CC(C)C)NC([C@H](C(C)(C)C)NC([C@@H](NC([C@@H]1CCCN1C([C@H](CCCNC(N)=N)NC([C@H](CCCNC(N)=N)NC(CCN2C([C@@H](NC([C@@H](CCCNC(N)=N)NC([C@@H](N)CC3=C(C)C=C(O)C=C3C)=O)=O)CC4=C(C=CC=C4)C2)=O)=O)=O)=O)=O)CC(C(C)=C5)=C(C)C=C5O)=O)=O)=O,1.11 ± 0.39,159 ± 94,102 ± 8.0,0.78 ± 0.2,0.03 ± 0.03
6,OC([C@H](CC(C)C)NC([C@H](C(C)(C)C)NC([C@@H](NC([C@@H]1CCCN1C([C@H](CCCCN)NC([C@H](CCCCN)NC(CCN2C([C@@H](NC([C@@H](CCCNC(N)=N)NC([C@@H](N)CC3=C(C)C=C(O)C=C3C)=O)=O)CC4=C(C=CC=C4)C2)=O)=O)=O)=O)=O)CC(C(C)=C5)=C(C)C=C5O)=O)=O)=O,7.15 ± 0.83,276 ± 42,138 ± 16,13 ± 1.3,0.16 ± 0.05
7,OC([C@H](CC(C)C)NC([C@H](C(C)(C)C)NC([C@@H](NC([C@@H]1CCCN1C([C@H](CCCNC(N)=N)NC(C[C@@H](NC(CCN2C([C@@H](NC([C@@H](CCCNC(N)=N)NC([C@@H](N)CC3=C(C)C=C(O)C=C3C)=O)=O)CC4=C(C=CC=C4)C2)=O)=O)CCCNC(N)=N)=O)=O)=O)CC(C(C)=C5)=C(C)C=C5O)=O)=O)=O,1.75 ± 0.43,101 ± 2,27.9 ± 4.1,4.0 ± 0.05,0.003 ± 0.001
8,OC([C@H](CC(C)C)NC([C@H](C(C)(C)C)NC([C@@H](NC([C@@H]1CCCN1C([C@H](CCCCN)NC(C[C@H](CCCCN)NC(CCN2C([C@@H](NC([C@@H](CCCNC(N)=N)NC([C@@H](N)CC3=C(C)C=C(O)C=C3C)=O)=O)CC4=C(C=CC=C4)C2)=O)=O)=O)=O)=O)CC(C(C)=C5)=C(C)C=C5O)=O)=O)=O,7.12 ± 2.0,48.6 ± 5.7,208 ± 76,15 ± 2,0.32 ± 0.5
9,OC([C@H](CC(C)C)NC([C@@H](C(C)(C)C)NC([C@H](CC(C=C(O)C=C1)=C1C2)N2C([C@@H]3CCCN3C([C@H](CCCNC(N)=N)NC([C@H](CCCNC(N)=N)NC(CCN4C([C@@H](NC([C@@H](CCCNC(N)=N)NC([C@@H](N)CC5=C(C)C=C(O)C=C5C)=O)=O)CC6=C(C=CC=C6)C4)=O)=O)=O)=O)=O)=O)=O)=O,1.67 ± 0.16 ,105 ± 35,22.4 ± 1.6,4710 ± 580,1.72 ± 4.0
10,OC([C@H](CC(C)C)NC([C@H](C(C)(C)C)NC([C@H](CC(C=C(O)C=C1)=C1C2)N2C([C@@H]3CCCN3C([C@H](CCCCN)NC([C@H](CCCCN)NC(CCN4C([C@@H](NC([C@@H](CCCNC(N)=N)NC([C@@H](N)CC5=C(C)C=C(O)C=C5C)=O)=O)CC6=C(C=CC=C6)C4)=O)=O)=O)=O)=O)=O)=O)=O,6.24 ± 0.48,209 ± 25,150 ± 53,6830 ± 4000,75 ± 80
11,OC([C@H](CC(C)C)NC([C@H](C(C)(C)C)NC([C@@H](NC([C@@H]1CCCN1C([C@H](CCCNC(N)=N)NC([C@H](CCCNC(N)=N)NC(CCN2C([C@@H](NC([C@@H](CCCNC(N)=N)NC([C@@H](N)CC3=C(C)C=C(O)C=C3C)=O)=O)CC4=C(C=CC=C4)C2)=O)=O)=O)=O)=O)CC5=CC=CC(O)=C5)=O)=O)=O,1.73 ± 0.62 ,60.9 ± 8.6,19.9 ± 4.2,12.4 ± 0.9,0.33 ± 0.04
12,OC([C@H](CC(C)C)NC([C@H](C(C)(C)C)NC([C@@H](NC([C@@H]1CCCN1C([C@H](CCCCN)NC([C@H](CCCCN)NC(CCN2C([C@@H](NC([C@@H](CCCNC(N)=N)NC([C@@H](N)CC3=C(C)C=C(O)C=C3C)=O)=O)CC4=C(C=CC=C4)C2)=O)=O)=O)=O)=O)CC5=CC=CC(O)=C5)=O)=O)=O,3.99 ± 0.97,200 ± 73,70.9 ± 15.1,59 ± 1.5,0.50 ± 0.45
13,OC([C@H](CC(C)C)NC([C@H](C(C)(C)C)NC([C@@H](NC([C@@H]1CCCN1C([C@H](CCCNC(N)=N)NC(C[C@@H](N)CCCNC(N)=N)=O)=O)=O)CC(C(C)=C2)=C(C)C=C2O)=O)=O)=O,,,,2.3 ± 0.2,0.11 ± 0.07
14,OC([C@H](CC(C)C)NC([C@H](C(C)(C)C)NC([C@@H](NC([C@@H]1CCCN1C([C@H](CCCNC(N)=N)NC([C@H](CCCNC(N)=N)N)=O)=O)=O)CC(C(C)=C2)=C(C)C=C2O)=O)=O)=O,,,,13.4 ± 2.0,3.0 ± 2.0
15,OC([C@H](CC(C)C)NC([C@@H](C(C)(C)C)NC([C@H](CC(C=C(O)C=C1)=C1C2)N2C([C@@H]3CCCN3C([C@H](CCCNC(N)=N)NC([C@H](CCCNC(N)=N)N)=O)=O)=O)=O)=O)=O,,,,6680 ± 3700,132 ± 47
16,OC([C@H](CC(C)C)NC([C@H](C(C)(C)C)NC([C@@H](NC([C@@H]1CCCN1C([C@H](CCCNC(N)=N)NC([C@H](CCCNC(N)=N)N)=O)=O)=O)CC2=CC=CC(O)=C2)=O)=O)=O,,,,93.0 ± 22,24.0 ± 18
PK20,OC([C@H](CC(C)C)NC([C@H](C(C)(C)C)NC([C@@H](NC([C@@H]1CCCN1C([C@H](CCCCN)NC([C@H](CCCCN)NC([C@H](CC2=CC=CC=C2)NC([C@H](CC3=CC=CC=C3)NC([C@@H](CCCCN)NC([C@H](CC4=C(C)C=C(O)C=C4C)N)=O)=O)=O)=O)=O)=O)=O)CC5=CC=CC=C5)=O)=O)=O,4.13 ± 1.4,46.4 ± 3.6,33.5 ± 6.2,188 ± 29,29.5 ± 11