Abstract

The objectives of this proposal are: (1) the preparation of kappa and delta selective ligands of suitable potency so that they can be employed in affinity chromatography to isolate and purify kappa and delta opioid receptors and (2) the preparation of a new type of photoaffinity label. The kappa ligands which we plan to prepare are related to tifluadom and the highly selective U-50488 and U- 69583. The photoaffinity labels are derived from photolabile substituted cyclohexadienones which can be coupled to derivatives related to such opiates as fentanyl and etonitazene.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA001674-11
Application #
3206983
Study Section
Pharmacology I Research Subcommittee (DABR)
Project Start
1977-06-01
Project End
1990-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
11
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Rensselaer Polytechnic Institute
Department
Type
Schools of Arts and Sciences
DUNS #
002430742
City
Troy
State
NY
Country
United States
Zip Code
12180

  Publications

Archer, S; Seyed-Mozaffari, A; Jiang, Q et al. (1994) 14 alpha,14' beta-[Dithiobis[(2-oxo-2,1-ethanediyl)imino]]bis (7,8-dihydromorphinone) and 14 alpha,14' beta-[dithiobis[(2-oxo-2,1- ethanediyl)imino]]bis[7,8-dihydro-N-(cyclopropylmethyl)normorphinone]: chemistry and opioid binding properties. J Med Chem 37:1578-85
Simon, E J; Fan, L Q; Hiller, J M et al. (1993) Photoaffinity ligands for the mu opioid receptor. Life Sci 53:1173-8
Sebastian, A; Bidlack, J M; Jiang, Q et al. (1993) 14 beta-[(p-nitrocinnamoyl)amino]morphinones, 14 beta-[(p-nitrocinnamoyl)amino]-7,8-dihydromorphinones, and their codeinone analogues: synthesis and receptor activity. J Med Chem 36:3154-60
Jiang, Q; Seyed-Mozaffari, A; Archer, S et al. (1993) Pharmacological study of 14 beta-(thioglycolamido)-7,8-dihydro-N(cyclopropylmethyl)-normor phinone (N-CPM-TAMO). J Pharmacol Exp Ther 264:1021-7
Bidlack, J M; Kaplan, R A; Subbramanian, R A et al. (1993) Affinity labeling of the mu opioid receptor in bovine striatal membranes with [3H]-14 beta-(bromoacetamido)-7,8-dihydromorphine. Biochemistry 32:6703-11
Jiang, Q; Seyed-Mozaffari, A; Archer, S et al. (1993) Antinociceptive evaluation of 14 beta-(bromoacetamido)-7,8-dihydro- N(cyclopropylmethyl)-normorphinone in mice. Eur J Pharmacol 240:201-6
Jiang, Q; Seyed-Mozaffari, A; Archer, S et al. (1992) Antinociceptive properties of two alkylating derivatives of morphinone: 14 beta-(thioglycolamido)-7,8-dihydromorphinone (TAMO) and 14 beta-(bromoacetamido)-7,8-dihydromorphinone (H2BAMO). J Pharmacol Exp Ther 262:526-31
Archer, S; Medzihradsky, F; Seyed-Mozaffari, A et al. (1992) Synthesis and characterization of 7-nitrobenzo-2-oxa-1,3-diazole (NBD)-labeled fluorescent opioids. Biochem Pharmacol 43:301-6
Archer, S; Bidlack, J; Mulholland, G K (1990) Opium alkaloids and affinity labels. NIDA Res Monogr 96:21-34
Bidlack, J M; Frey, D K; Kaplan, R A et al. (1990) Affinity labeling of mu opioid receptors by sulfhydryl alkylating derivatives of morphine and morphinone. Mol Pharmacol 37:50-9

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