Corrigendum to “Epibatidine structure–activity relationships”

Bioorganic & Medicinal Chemistry Letters
2004.0

Abstract

A correction to Ref. 25 in this review article was published in June 2004 J. Chem. Soc., Perkin Trans. Issue. The correction showed that the data reviewed in Table 9 (page 1893) for structures 12 and 15 should be transposed and the discussion on page 1894 updated. The revised discussion notes that the 5- and 6-(20 -chloro-50 -pyridinyl)heptanes 12–15 are epibatidine analogs where the 7-position nitrogen of epibatidine (1) has been moved to the 5- or 6-position of the 7-azabicyclo[2.2.1] ring. Cox et al. synthesized all four analogs and evaluated their a4b2 and a7 nAChR potency for inhibition of [3H]nicotine binding to rat cortical membranes and [125I]BTX binding in rat hippocampal membranes, respectively: 14 and 15 with Ki values of 0.045 nM and 0.056 nM for a4b2 nAChRs were almost as potent as epibatidine (1) (Ki 0.02 nM), compounds 12 and 14 showed Ki values of 1600 and 3.9 nM for a7 nAChR, and compounds 12 and 13 possessed low affinity for both. Dart and coworkers also synthesized analogs 12–14 and evaluated their a4b2 nAChR potency using whole rat brain tissue and [3H]cytisine as the radioligand, finding 14 (Ki 0.032 nM) equipotent to epibatidine (Ki 0.04 nM) and analog 12 to have relatively low affinity. The revised Table 9 is included.

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