PMID: 11902645Mar 21, 2002Paper

Synthesis of (+)- and (-)-cis-2-[(1-adamantylamino)-methyl]-1-phenylcyclopropane derivatives as high affinity probes for sigma1 and sigma2 binding sites

Il Farmaco
A MarrazzoG Ronsisvalle

Abstract

Selective ligands for either sigma1 (sigma1) or sigma2 binding sites are potentially useful for gaining a better understanding of the physiological functions of these proteins. Moreover, potent and selective homochiral sigma1 and sigma2 binding site ligands represent leads to potential radioligands for tumour imaging with positron emission tomography (PET). On the basis of their structural similarity to previous leads, new (+)- and (-)-cis-2-[(1-adamantylamino)-methyl]-1-phenylcyclopropane derivatives were synthesised and their binding affinities for sigma1 and sigma2 binding sites were determined. Each enantiomer showed high affinity for both sigma1 and sigma2 binding sites, but only (-)-cis-methyl-2-[[1-adamantyl(methyl)amino]methyl]-1-phenylcyclopropane-carboxylate, (-)-4, showed appreciable selectivity for binding to sigma1 versus sigma2 sites. The enantiomers of cis-(2-[[1-adamantyl(methyl)amino]methyl]-1-phenylcyclopropyl)methanol, 6, expressed the highest affinity for sigma1 and sigma2 binding sites. Ligands (-)-4, (+)-6 and (-)-6 might be rapidly labelled in their N-methyl groups by methylation of the N-desmethyl analogues with [11C]iodomethane to provide prospective radioligands for PET. The N-desmethyl analogues, whic...Continue Reading

References

Mar 1, 1992·Trends in Pharmacological Sciences·R QuirionD P Taylor
Dec 1, 1992·European Journal of Pharmacology·D L DeHaven-HudkinsF Y Ford-Rice
Nov 1, 1985·Journal of Pharmacological Methods·G A McPherson
Apr 25, 1995·Proceedings of the National Academy of Sciences of the United States of America·F P MonnetE E Baulieu
Jun 23, 1994·European Journal of Pharmacology·M L LeitnerJ M Walker
Jul 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·M HannerH Glossmann
Dec 13, 1996·Biochemical and Biophysical Research Communications·R KekudaV Ganapathy
Jul 16, 1997·European Journal of Pharmacology·M KingG W Pasternak
Mar 9, 2000·Nuclear Medicine and Biology·K KawamuraM Senda
May 17, 2000·Pharmaceutica acta Helvetiae·W D Bowen
Jul 15, 2000·Bioorganic & Medicinal Chemistry·G RonsisvalleS Spampinato
Jan 10, 2001·Proceedings of the National Academy of Sciences of the United States of America·T Hayashi, T P Su

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Citations

Jul 14, 2005·Neuroreport·Agostino MarrazzoGiuseppe Ronsisvalle
Aug 26, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Markos-Orestis GeorgiadisIoannis Papanastasiou
Feb 16, 2021·Medicinal Chemistry Research : an International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents·Sebastiano IntagliataChristopher R McCurdy
Jun 3, 2021·Journal of Medicinal Chemistry·Antonino N FallicaSebastiano Intagliata
Apr 12, 2011·Journal of Medicinal Chemistry·Agostino MarrazzoGiuseppe Ronsisvalle

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