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. Author manuscript; available in PMC: 2019 Aug 13.
Published in final edited form as: J Med Chem. 2018 Aug 29;61(17):7525–7545. doi: 10.1021/acs.jmedchem.8b00673

Table 3.

Inhibition of Agonist-Stimulated [35S]GTPγS Binding in Cloned Human μ, δ, and κ Opioid Receptors, Importance of the Piperidine 4-Methyl Group

graphic file with name nihms-1043744-t0018.jpg
compd R1 R2 Ke (nM)a
 μ/κ δ/κ
μ, DAMGO δ, DPDPE κ, U69,593
12 CH3 H 239 ± 22 >3000 0.37 ± 0.09 645 >8100
18 CH3 CH3 142 ± 25 847 ± 180 3.57 ± 1.5 40 >237
19 CH2CH3 H 74.8 ± 23 2490 ± 620 2.48 ± 0.70 30 1004
20 CF3 H 67.9 ± 12 >3000 4.69 ± 0.29 14 >640
21 CHF2 H 70.9 ± 9.4 >3000 3.45 ± 1.2 21 >870
22 OCH3 H 198 ± 48 >3000 6.53 ± 1.8 30 >459
23 N(CH3)2 H 318 ± 8.4 >3000 8.08 ± 1.2 39 >371
24 F F 604 ± 83 >3000 11.8 ± 3.0 51 >254
25 CN H 647 ± 150 >3000 12.7 ± 3.1 51 >236
26 CONH2 H 129 ± 26 >3000 3.22 ± 0.78 40 >932
a

Data are mean ± SEM of at least three independent experiments conducted in duplicate. None of the compounds had agonist activity at 10 μM.