Synthesis and evaluation of 4-alkoxy-[1'-cyclobutyl-spiro(3,4-dihydrobenzopyran-2,4'-piperidine)] analogues as histamine-3 receptor antagonists |
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| Authors: | Becknell Nadine C Dandu Reddeppa Reddy Lyons Jacquelyn A Aimone Lisa D Raddatz Rita Hudkins Robert L |
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| Institution: | Discovery Research, Cephalon, Inc., 145 Brandywine Parkway, West Chester, PA 19380, USA. nbecknell@cephalon.com |
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| Abstract: | A novel class of 4-alkoxy-1'-cyclobutyl-spiro(3,4-dihydrobenzopyran-2,4'-piperidine)] analogues were designed and synthesized as H(3)R antagonists. Structure-activity relationship identified sulfone 27 with excellent H(3)R affinities in both humans and rats, and acceptable pharmacokinetic properties. Further, compound 28 achieved single digit nanomolar H(3)R affinities in both species with minimum hERG activity. |
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