N-(3-( sup 18 F)fluoropropyl)-N-nordiprenorphine: Synthesis and characterization of a new agent for imaging opioid receptors with positron emission tomography

Journal Article · Tue May 01 04:00:00 EDT 1990 · Journal of Medicinal Chemistry; (USA)

DOI:https://doi.org/10.1021/jm00167a031· OSTI ID:6870402

Chesis, P L; Hwang, D R; Welch, M J ^[1]

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1. Washington Univ. School of Medicine, St. Louis, MO (USA)

A series of N-fluoroalkyl (1-5) and N-alkyl (6-8) analogues of the high-affinity opioid receptor antagonist diprenorphine (9) has been synthesized and evaluated with in vitro binding assays. Three of the N-fluoroalkyl compounds were prepared with the positron-emitting radionuclide {sup 18}F (1a, 2a, 5a), and their biodistribution was determined in rats. Compounds 2a and 5a were made by using a two-step labeling procedure, ({sup 18}F)fluoride displacement of an iodoalkyl triflate followed by N-alkylation, that required 2 h and proceeded in 4-6% overall radiochemical yield at the end of synthesis. The effective specific activity of compounds 2a and 5a, determined by competitive receptor binding assay, was 840-1820 Ci/mmol. Compound 1a was made by the same two-step procedure, with the bromoalkyl triflate, in 0.3-0.6% radiochemical yield at an effective specific activity of 106-264 Ci/mmol. Specificity of binding in vivo was measured as the percent injected dose/gram of striatal tissue divided by the percent injected dose/gram of cerebellar tissue. The best striatum to cerebellum ratio (3.32 +/- 0.74 at 30 min) was achieved with N-(3-({sup 18}F)-fluoropropyl)-N-nordiprenorphine (2a, ({sup 18}F)FPND). The high specific binding demonstrated by this compound indicates that it may be useful for in vivo imaging of opioid receptors with positron emission tomography.

• OSTI ID: 6870402
• Journal Information: Journal of Medicinal Chemistry; (USA), Journal Name: Journal of Medicinal Chemistry; (USA) Vol. 33:5; ISSN JMCMA; ISSN 0022-2623
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ALKYLATION
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CHEMICAL PREPARATION
CHEMICAL REACTIONS
DISTRIBUTION
DRUGS
ENDORPHINS
FLUORINE 18
FLUORINE ISOTOPES
HOURS LIVING RADIOISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LABELLING
LIGANDS
LIGHT NUCLEI
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIOISOTOPES
RADIOPHARMACEUTICALS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
STRUCTURE-ACTIVITY RELATIONSHIPS
SYNTHESIS
TISSUE DISTRIBUTION
VERTEBRATES