Table 1. Data for Spiro-azetidino-piperidine Analogues 10, 11, and 16a–h.

^aelogD = measured logD at pH 7.4 [calculated logD (ACD Laboratories program v12) in parentheses].

^bTPSA = topological polar surface area.

^cGeometric mean ± standard error of ≥3 measurements (unless noted otherwise).

^dHuman ghrelin receptor SPA receptor binding assay as published.²⁷

^eHuman ghrelin receptor agonist/antagonist/inverse agonist GTP-γ-S functional assay as published.²⁷

^fMinimum percent effect in parentheses; a negative value indicates an inverse agonist.

^gMuscarinic M2 β-Arrestin PathHunter assay from Discoverx. K_b for antagonists determined in the presence of EC₈₀ concentration of agonist, oxotremorine.³⁹

^hRatio of M2 K_b over human ghrelin receptor functional K_i values.

ⁱHuman liver microsome (HLM) apparent intrinsic clearance, mL/min/kg, uncorrected for fraction unbound.

^jPassive permeability (P_app in 10^–6 cm/s) measured using low-efflux MDCKII cells as described.⁴⁰

^kMDR BA/AB efflux ratio using MDCK cell line transfected with human MDR1.⁴¹

^lLess than three independent replicates.