Synthesis and evaluation of 4-alkoxy-[1′-cyclobutyl-spiro (3, 4-dihydrobenzopyran-2, 4′-piperidine)] analogues as histamine-3 receptor antagonists

…, JA Lyons, LD Aimone, R Raddatz, RL Hudkins

文献索引：Becknell, Nadine C.; Dandu, Reddeppa Reddy; Lyons, Jacquelyn A.; Aimone, Lisa D.; Raddatz, Rita; Hudkins, Robert L. Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 1 p. 186 - 189

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被引用次数: 9

摘要

A novel class of 4-alkoxy-[1′-cyclobutyl-spiro (3, 4-dihydrobenzopyran-2, 4′-piperidine)] analogues were designed and synthesized as H3R antagonists. Structure–activity relationship identified sulfone 27 with excellent H3R affinities in both humans and rats, and acceptable pharmacokinetic properties. Further, compound 28 achieved single digit nanomolar H3R affinities in both species with minimum hERG activity.