7-Arylidenenaltrexones as selective δ1 opioid receptor antagonists

S. Ohkawa, P. S. Portoghese

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11 Scopus citations


A series of 7-arylidinenaltrexones (2a-m) related to the prototypical δ1-selective antagonist, 7-benzylidenenaltrexone 1 (BNTX), have been synthesized in an effort to develop more selective ligands. Testing in smooth muscle preparations revealed that members of the series exhibited varying degrees of selectively for δ receptors, with the o-methoxy (2e) and o- chloro (2j) congeners being most potent and most selective (Ke ~ 0.8 nm). Evaluation of 1, 2e, and 2f sc in mice using the tail-flick procedure indicated that they are selective δ1 opioid receptor antagonists in the lower dose range. At high doses these ligands, including BNTX, exhibited decreased δ1 selectivity due to increases in the ED50 ratios of [D- Ser2,Leu5]enkephalin-Thr6 and morphine. It is concluded that 2e and 2f possess in vivo selectivity similar to that of BNTX, but are less potent as δ1 antagonists.

Original languageEnglish (US)
Pages (from-to)4177-4180
Number of pages4
JournalJournal of medicinal chemistry
Issue number21
StatePublished - Oct 8 1998


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