Preparation and properties of (R)-(-)-1-azabicyclo(2. 2. 2)oct-3-yl- (R)-(+)-alpha-hydroxy-alpha-(4-( sup 125 I)iodophenyl)-alpha-phenyl acetate and (R)-(-)-1-azabicyclo(2. 2. 2)oct-3-yl-(S)-(-)-alpha-hydroxy-alpha- (4-( sup 125 I)iodophenyl)-alpha-phenyl acetate as potential radiopharmaceuticals

Journal Article · Sun Oct 01 04:00:00 EDT 1989 · Journal of Pharmaceutical Sciences; (USA)

DOI:https://doi.org/10.1002/jps.2600781011· OSTI ID:7244564

Cohen, V I; Rzeszotarski, W J; Gibson, R E; Fan, L H; Reba, R C ^[1]

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1. George Washington Univ. Medical Center, Washington, DC (USA)

rac-4-Nitrobenzilic acid was synthesized and resolved with quinidine and quinine to give the corresponding (R)- and (S)-salts. The resolved diastereomeric salts were converted to (R)- and (S)-4-nitrobenzilic acids and subsequent esterification gave their corresponding ethyl esters. Transesterification with (R)-(-)-3-quinuclidinol afforded (R)-(-)-1-azabicyclo(2.2.2)oct-3-yl-(R)-(+)-alpha-hydroxy-alpha- (4-nitrophenyl)-alpha-phenyl acetate and (R)-(-)-1-azabicyclo(2.2.2)oct-3-yl-(S)-(-)-alpha-hydroxy- alpha-(4-nitrophenyl)-alpha-phenyl acetate. After hydrogenation, the (R,R)- and (R,S)-amines were converted to the respective triazene derivatives. The triazene derivatives reacted with sodium ({sup 125}I)iodide to give (R)-(-)-1-azabicyclo(2.2.2)oct-3-yl-(R)-(+)- alpha-hydroxy-alpha-(4-({sup 125}I)iodophenyl)-alpha-phenyl acetate and (R)-(-)-1-azabicyclo(2.2.2)oct-3-yl-(S)-(-)-alpha-hydroxy- alpha-(4-(125I)iodophenyl)-alpha-phenyl acetate. The evaluation of their affinities to muscarinic acetylcholine receptors (MAcChR) shows that (R)-(-)-1-azabicyclo(2.2.2)oct-3-yl-(S)-(-)-alpha-hydroxy-alpha-(4- ({sup 125}I)iodophenyl)-alpha-phenyl acetate exhibits an affinity for the MAcChR from corpus striatum that is approximately threefold lower than that of (R)-(-)-1-azabicyclo(2.2.2)oct-3-yl-(R)-(+)-alpha-hydroxy-alpha-(4- ({sup 125}I)iodophenyl)-alpha-phenyl acetate.

• OSTI ID: 7244564
• Journal Information: Journal of Pharmaceutical Sciences; (USA), Journal Name: Journal of Pharmaceutical Sciences; (USA) Vol. 78:10; ISSN JPMSA; ISSN 0022-3549
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ACETYLCHOLINE
AMINES
AMMONIUM COMPOUNDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
CHEMICAL PREPARATION
CHEMICAL PROPERTIES
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ESTERIFICATION
ESTERS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PARASYMPATHOMIMETICS
PROTEINS
QUATERNARY COMPOUNDS
RADIOISOTOPES
RADIOPHARMACEUTICALS
RATS
RECEPTORS
RODENTS
SYNTHESIS
VERTEBRATES