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. Author manuscript; available in PMC: 2021 May 28.
Published in final edited form as: J Med Chem. 2020 May 12;63(10):5526–5567. doi: 10.1021/acs.jmedchem.0c00424

Table 3.

Analogs exploring modification of the tether or piperazine core.

Compound ID Structure D3R agonist activity1 D2R agonist activity1 D2R antagonist activity1
EC50 (nM) Emax (% control) EC50 (nM) Emax (% control) IC50 (nM) Imax (% control)
46 graphic file with name nihms-1592058-t0005.jpg 9,300 ± 2,500 106 ± 11 Inactive Inactive >100,000 ND
47 graphic file with name nihms-1592058-t0006.jpg 160 ± 33 86 ± 7 Inactive Inactive 18,000 ± 2,900 89 ± 7
48 graphic file with name nihms-1592058-t0007.jpg 4,400 ± 2,300 55 ± 7 Inactive Inactive >100,000 ND
49 graphic file with name nihms-1592058-t0008.jpg 510 ± 110 101 ± 7 4,200 ± 900 29 ± 1 >100,000 ND
50 graphic file with name nihms-1592058-t0009.jpg Inactive Inactive Inactive Inactive Inactive Inactive
51 graphic file with name nihms-1592058-t0010.jpg Inactive Inactive Inactive Inactive 18,000 ± 4,800 72 ± 4.6
1

β-arrestin recruitment activity was assessed as described in Figure 2. Emax values are expressed as a percentage of the maximum dopamine response observed in the same assay. Imax values are expressed as a percentage of the maximum inhibition of a dopamine (EC80 concentration) response observed with the antagonist sulpiride in the same assay.

ND Curve did not plateau.