Design, synthesis, and evaluation of omega-iodovinyl- and omega-iodoalkyl-substituted methyl-branched long-chain fatty acids
The synthesis of a new methyl-branched fatty acid, (E)-19-iodo-3(RS)-methyl-18-nonadecenoic acid (19), is described. Methyl branching has been introduced at the 3-position to inhibit beta-oxidation and radioiodide has been attached as a trans-vinyl iodide. Preparation of 19 involved a 15-step sequence of reactions climaxing with formation of the methyl ester 18 by iododestannylation of methyl (E)-19-(tri-n-butylstannyl)-3(RS)-methyl-18-nonadecenoate (17) resulting from the reaction of n-Bu3SnH with methyl 3(RS)-methyl-18-nonadecynoate (16). Methyl branching was introduced at an early stage by Friedel-Crafts acylation of thiophene with 3(RS)-methyl-4-carbomethoxybutanoyl chloride (3) generated from 3-methylglutaric anhydride. The new agent, (/sup 125/I)-19, showed high myocardial uptake (5 min, 4.89% dose/g; 30 min, 3.32% dose/g), good heart/blood (H/B) ratios (5 min, 5.4/1; 30 min, 4.3/1), and significantly greater myocardial retention in fasted rats than the corresponding straight-chain analogue 19-(/sup 125/I)-iodo-18-nonadecenoic acid (5 min, 3.52% dose/g, H/B = 4.8/1; 30 min, 1.19% dose/g, H/B = 1.6/1). Excellent myocardial images were obtained in rats after administration of (123I)-19 and confirmed the slow myocardial washout over a 60-min period. These data suggest that 19 is a good candidate for evaluation of heart disease involving aberrations in fatty acid metabolism by use of imaging techniques such as single photon emission computerized tomography (SPECT) where redistribution or washout should be minimized.
- Research Organization:
- Oak Ridge National Lab., TN
- OSTI ID:
- 5253758
- Journal Information:
- J. Med. Chem.; (United States), Vol. 6
- Country of Publication:
- United States
- Language:
- English
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BIOSYNTHESIS
TISSUE DISTRIBUTION
HYPERTENSION
IODINE 125
METABOLISM
MYOCARDIUM
RATS
RETENTION
SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
CARDIOVASCULAR DISEASES
CARDIOVASCULAR SYSTEM
COMPUTERIZED TOMOGRAPHY
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC TECHNIQUES
DISEASES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
EMISSION COMPUTED TOMOGRAPHY
HEART
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
MAMMALS
MUSCLES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
RADIOISOTOPES
RODENTS
SYMPTOMS
SYNTHESIS
TOMOGRAPHY
VASCULAR DISEASES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques