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. Author manuscript; available in PMC: 2017 Oct 19.
Published in final edited form as: ACS Chem Neurosci. 2017 Jul 26;8(10):2315–2324. doi: 10.1021/acschemneuro.7b00226

Table 2.

Binding and in Vitro Activity at the Opioid and NK1 Receptorsa

compd no. structure NK1Rb NK1R GPId MVDd MOPe DOPe
Ki (nM) pA2c IC50 (nM) IC50 (nM) Ki (nM) Ki (nM)
1f H-Dmt-D-Arg-Aba-Gly-NH2 nd nd 0.32 0.42 0.15 0.60
2g H-Dmt-D-Arg-Aba-β-Ala-NH2 nd nd 0.80 0.24 1.34 17.0
3f H-Dmt-D-Arg-Aba-Gly-NMe-3′,5′-(CF3)2-Bn 0.5 7.80 8.51 43.3 0.42 10.4
4g H-Dmt-D-Arg-Aba-β-Ala-NMe-Bn 13.0 6.44 1.86 2.16 0.08 0.28
5g H-Dmt-D-Arg-Aba-Gly-NMe-Bn 1530 nd 5.97 8.64 0.09 2.35
6 H-Dmt-D-Arg-Aba-β-Ala-NcPr-3′,5′-(CF3)2-Bn 735 5.36 18 16 47 190
7 H-Dmt-D-Arg-Aba-β-Ala-NcPr-Bn 520 5.20 19 6.6 2.7 66
8 H-Dmt-D-Arg-Aba-Gly-NcPr-Bn 95 5.50 10 11.2 0.30 68
9 H-Dmt-D-Arg-Aba-β-Ala-isoindoline >10 000 0.25 5 2.1 0.20 16
10 H-Dmt-D-Arg-Aba-Gly-isoindoline 3495 3.16 7.3 8.0 0.06 81
11 H-Dmt-D-Arg-Aba-Gly-NMe-2′-OMe-Bn 501 4.84 5.0 2.4 0.90 26
12 H-Dmt-D-Arg-Aba-β-Ala-NMe-2′-methylenenaphthyl 612 7.01 9.0 4.0 0.40 44
13 H-Dmt-D-Arg-Aba-Gly-NMe-2′-methylenenaphthyl 709 5.44 3.0 10.0 2.8 228
a

Results of the compounds selected for in vivo testing are shown in bold. nd: not determined.

b

Binding affinities of compounds for hNK1 receptors were determined by displacement of [3H]substance P from binding sites in hNK1 receptors expressed in CHO cells.

c

The pA2 values were calculated using Schild’s equation.22

d

The GPI functional assay is representative of MOP receptor activation, whereas the MVD is a DOP receptor-representative assay.

e

Binding affinities of compounds for MOP and DOP receptors were determined by displacement of [3H]DAMGO ([D-Ala2,NMePhe4,Gly-ol5]enkephalin) and [3H]DSLET ([D-Ser2,Leu5]enkephalin-Thr6), respectively, from rat brain membrane binding sites.

f

Data from Ballet et al.1

g

Data from Guillemyn et al.2