Abstract

Significant progress was made in the last reporting period, resulting in five publications. We reported on the synthesis and opioid binding affinity of the final pair of oxide-bridged phenylmorphans, the ortho- and para-b-isomers and their N-phenethyl analogues, and the synthesis of the N-phenethyl analogues of the ortho- and para-d-isomers. Another study described the synthesis and pharmacological effects of the enantiomers of the N-phenethyl analogues of the ortho and para e- and f-oxide-bridged phenylmorphans. We also reported the design, synthesis, and characterization of 6beta-naltrexol analogs, and their selectivity for in vitro opioid receptor subtypes and provided new information on the role of the furan in affinity of neoclerodane diterpenes from Salvia divinorum for opioid receptors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIADA000525-02
Application #
7966895
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2009
Total Cost
$601,275
Indirect Cost

  Institution

Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Sally, Elliott J; Xu, Heng; Dersch, Christina M et al. (2010) Identification of a novel ""almost neutral"" micro-opioid receptor antagonist in CHO cells expressing the cloned human mu-opioid receptor. Synapse 64:280-8
Iyer, Malliga R; Lee, Yong Sok; Deschamps, Jeffrey R et al. (2010) Probes for narcotic receptor mediated phenomena. 40. N-substituted cis-4a-ethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-8-ols. Bioorg Med Chem 18:91-9
Hsin, Ling-Wei; Chang, Li-Te; Rothman, Richard B et al. (2010) Synthesis and opioid activity of enantiomeric N-substituted 2,3,4,4a,5,6,7,7a-octahydro-1H-benzofuro[3,2-e]isoquinolines. J Med Chem 53:1392-6
Zhang, Yi; Lee, Yong Sok; Rothman, Richard B et al. (2009) Probes for narcotic receptor mediated phenomena. 39. Enantiomeric N-substituted benzofuro[2,3-c]pyridin-6-ols: synthesis and topological relationship to oxide-bridged phenylmorphans. J Med Chem 52:7570-9
Simpson, Denise S; Lovell, Kimberly M; Lozama, Anthony et al. (2009) Synthetic studies of neoclerodane diterpenes from Salvia divinorum: role of the furan in affinity for opioid receptors. Org Biomol Chem 7:3748-56
Pelotte, Andrea L; Smith, Ryan M; Ayestas, Mario et al. (2009) Design, synthesis, and characterization of 6beta-naltrexol analogs, and their selectivity for in vitro opioid receptor subtypes. Bioorg Med Chem Lett 19:2811-4
Kurimura, Muneaki; Liu, Hehua; Sulima, Agnieszka et al. (2008) Probes for narcotic receptor mediated phenomena. 37. Synthesis and opioid binding affinity of the final pair of oxide-bridged phenylmorphans, the ortho- and para-b-isomers and their N-phenethyl analogues, and the synthesis of the N-phenethyl analogues of J Med Chem 51:7866-81
Zezula, Josef; Singer, Lisa; Przybyl, Anna K et al. (2008) Synthesis and pharmacological effects of the enantiomers of the N-phenethyl analogues of the ortho and para e- and f-oxide-bridged phenylmorphans. Org Biomol Chem 6:2868-83