Probes for narcotic receptor mediated phenomena. 47. Novel C4a- and N-substituted-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols.

Abstract:

:A series of N-methyl rac-cis-4a-aralkyl- and alkyl-substituted-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols have been prepared (2a-l) using a simple previously designed synthetic route, in order to find a ligand that would interact with both μ- and δ-opioid receptors. A C4a-phenethyl derivative 2a, was found to have modest receptor affinity both at μ- (K(i)=60 nM) and δ-opioid receptors (K(i)=64 nM). The N-methyl substituent of 2a and that of other ligands in the series was then modified to obtain compounds with different N-substituents that might provide higher affinity at both receptors. A number of compounds differently substituted at C4a and N were synthesized and evaluated. Binding studies and functional assays revealed a moderately selective δ-antagonist (2l), selective μ-δ antagonists (3d, 3g), and a μ-κ antagonist (3f).

journal_name

Bioorg Med Chem

authors

Iyer MR,Rothman RB,Dersch CM,Jacobson AE,Rice KC

doi

10.1016/j.bmc.2013.02.060

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

3298-309

issue

11

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(13)00262-9

journal_volume

21

pub_type

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