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125I]Tyr14-NC/OFQ, and agonist/antagonist
activities were measured by the [35S]GTPcS binding
method. Cross reactivity to other opioid receptors was
also tested. Affinities and agonist/antagonist activities for
human l-, j-, and d-receptors were assayed similarly to
ORL1 using membrane fractions of CHO cells expressed
in each receptor (Affinities were measured by displacement
of a [3H]diprenorphin for l, [3H]U-69593 for j and
[3H]naltrindole for d binding, respectively. Antagonist
activities were measured by DAMGO for l, U-69593 for j
and DADLE for d, respectively).
20. Human microsomal stability was determined by % parent
compound (1 lM) remaining after 30 min (37 ꢁC) incuba-
tion with human liver microsomes (0.25 mg protein/ml).
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J. Med. Chem. 1999, 42, 5061) was used as an internal
control across all assay plates for data validation.
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24. Analytical data for compound 8. 1H NMR (400 MHz,
CDCl3) d [ppm] 0.91 (3H, d, J = 6.4 Hz), 1.50 (9H, s),
2.25–2.96 (8H, m), 3.14–3.22 (1H, m), 3.35–3.45 (1H, m),
3.69 (2H, t, J = 5.2 Hz), 7.20–7.90 (2H, m), 9.50 (1H, br s).
MS (ESI+): m/z 383.2 (M+H)+.