Synthesis of iodine-125 labeled (+/-)-15-(4-azidobenzyl)carazolol: a potent beta-adrenergic photoaffinity probe
(+/-)-15-(4-Azidobenzyl)carazolol (2), a potent beta-adrenergic photoaffinity ligand has been radioiodinated to theoretical specific activity (2175 Ci/mmol) and shown to label covalently beta-adrenergic receptor peptides in avian and amphibian erythrocyte membrane preparations. The radioiodinated analogues of the desired compound (2) were optimally prepared by two synthetic steps from (+/-)-15-(4-aminobenzyl)carazolol (8). The latter was iodinated with carrier-free Na/sup 125/I and chloramine T to yield two major isotopomers (the monoiodinated derivatives 9 and 10), which were separated by thin-layer chromatography and converted via diazonium salt formation to their respective 4-azides, 12 and 6. These azides can be used interchangeably in ligand binding or photoaffinity labeling experiments. Compound 8 was obtained by catalytic reduction of the nitro derivative (7), which was arrived at by direct reaction of 1,1-dimethyl-2-(4-nitrophenyl)ethylamine (3) with 4-(2,3-epoxypropoxy)carbazole (5). Of the desired isomers, (+/-)-15-(4-azido-3-iodobenzyl)carazolol (6) could be synthesized from 1,1-dimethyl-2-(4-azido-3-iodophenyl)ethylamine (4) by direct reaction with 5. This and the preceding sequence of reactions were carried out by using nonradioactive materials, and separation and purification of products were accomplished by high-performance liquid chromatography. The compounds described have been shown to be potent beta-adrenergic antagonistsec The photoactive azide derivatives of these compounds (6 and 12) have been shown to covalently incorporate into the beta-adrenergic receptor binding subunit of frog and turkey erythrocyte membrane preparations. Incorporation of the ligands into these polypeptides can be blocked specifically by both beta-adrenergic agonists and antagonists.
- Research Organization:
- Department of Chemistry, Duke University, Durham, North Carolina
- OSTI ID:
- 5595993
- Journal Information:
- J. Med. Chem.; (United States), Vol. 26:6
- Country of Publication:
- United States
- Language:
- English
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Photoaffinity labeling adenosine A1 receptors with an antagonist /sup 125/I-labeled aryl azide derivative of 8-phenylxanthine
Related Subjects
IODINE 125
RADIOCHEMISTRY
RADIOPHARMACEUTICALS
CHEMICAL PREPARATION
AFFINITY
CELL MEMBRANES
ERYTHROCYTES
LABELLED COMPOUNDS
LABELLING
PHOTOCHEMISTRY
RECEPTORS
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL CONSTITUENTS
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
MATERIALS
MEMBRANES
NUCLEI
ODD-EVEN NUCLEI
RADIOISOTOPES
SYNTHESIS
400702* - Radiochemistry & Nuclear Chemistry- Properties of Radioactive Materials