Effects of alkyl and aryl substitution on the myocardial specificity of radioiodinated phosphonium, arsonium, and ammonium cations

Journal Article · Mon Jul 01 04:00:00 EDT 1985 · J. Med. Chem.; (United States)

DOI:https://doi.org/10.1021/jm00145a009· OSTI ID:5254126

Srivastava, P C; Hay, H G; Knapp, Jr, F F

Several radioiodinated iodopentenyl-trisubstituted phosphonium, arsonium, and ammonium iodides have been prepared and evaluated in rats to determine the effects of structural variations of the cations on myocardial uptake and retention. The synthesis of (E)-(1-iodo-1-penten-5-yl)-trisubstituted phosphonium, arsonium, and ammonium iodides via the condensation of trisubstituted phosphine, arsine, and amine precursors, respectively, with (E)-1,5-diiodopentene is described. In some cases a second route involved condensation with (E)-1-borono-5-iodo-1-pentene followed by iodination. In the phosphonium series, the compounds triphenyl 1, dicyclohexylphenyl 5, tricyclohexyl 6, and dimethyl-n-octyl 8 were prepared. The triphenylarsonium 10 and triethylammonium 11 compounds were also prepared. The corresponding radioiodinated analogues were prepared and tissue distribution studies performed in rats. The results (percent dose/gram, 30 min) demonstrate that replacement of phosphorus with arsenic (1, 3.99%; 10, 3.17%) or the replacement of the phenyl ring with the cyclohexyl ring system (6, 2.67%) has no apparent effect on heart uptake. In the series of compounds studied, replacement of the cyclic ring system with alkyl groups, however, significantly decreased heart uptake with both the phosphorus (8, 1.95%) and nitrogen agents (11, 1.11%). Gamma camera imaging studies with (/sup 123/I)-5 and (/sup 123/I)-8 further substantiated the decreased heart uptake with alkyl substitution and the apparent hepatobiliary clearance of 8.

• Research Organization: Oak Ridge National Lab., TN
• OSTI ID: 5254126
• Journal Information: J. Med. Chem.; (United States), Journal Name: J. Med. Chem.; (United States) Vol. 7; ISSN JMCMA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKYLATION
AMINES
AMMONIUM COMPOUNDS
ANIMALS
ARSENIC COMPOUNDS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CARDIOVASCULAR SYSTEM
CATIONS
CHARGED PARTICLES
CHEMICAL REACTIONS
CLEARANCE
COMPARATIVE EVALUATIONS
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
HEART
HOURS LIVING RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
IODINE 123
IODINE ISOTOPES
IONS
ISOTOPES
KINETICS
LABELLING
MAMMALS
MUSCLES
MYOCARDIUM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHOSPHINES
PHOSPHORUS COMPOUNDS
RADIOISOTOPES
RATS
REACTION KINETICS
RODENTS
STRUCTURE-ACTIVITY RELATIONSHIPS
TISSUE DISTRIBUTION
VERTEBRATES