- Positron emission tomography to elucidate pharmacokinetic differences of regioisomeric retinoid x receptor agonists
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RXR partial agonist NEt-4IB (2a, 6-[ethyl-(4-isobutoxy-3-isopropylphenyl)amino]pyridine-3-carboxylic acid: EC50 = 169 nM, Emax = 55%) showed a blood concentration higher than its Emax after single oral administration at 30 mg/kg to mice, and repeated oral administration at 10 mg/kg/day to KK-Ay mice afforded antitype 2 diabetes activity without the side effects caused by RXR full agonists. However, RXR full agonist NEt-3IB (1a), in which the isobutoxy and isopropyl groups of 2a are interchanged, gave a much lower blood concentration than 2a. Here we used positron emission tomography (PET) with tracers [11C]1a, [11C]2a and fluorinated derivatives [18F]1b, [18F]2b, which have longer half-lives, to examine the reason why 1a and 2a exhibited significantly different blood concentrations. As a result, the reason for the high blood concentration of 2a after oral administration was found to be linked to higher intestinal absorbability together with lower biliary excretion, compared with 1a.
- Kobayashi, Toshiki,Furusawa, Yuki,Yamada, Shoya,Akehi, Masaru,Takenaka, Fumiaki,Sasaki, Takanori,Akahoshi, Akiya,Hanada, Takahisa,Matsuura, Eiji,Hirano, Hiroyuki,Tai, Akihiro,Kakuta, Hiroki
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supporting information
p. 334 - 338
(2015/03/30)
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- ACYLOXYKETONE SUBSTITUTED IMINO AND AMINO ACIDS
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Acyloxyketone substituted imino and amino acids of the formula STR1 are disclosed. These compounds are useful hypotensive agents due to their angiotensin converting enzyme inhibition activity.
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- Synthesis of 2,6,10-trimethyl-undecan-1-ol
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A synthesis of 2,6,10-trimethyl-undecan-1-ol, an intermediate for producing vitamin E, from methacrolein, crotonaldehyde, β-hydroxy-isobutyric acid including intermediates in this synthesis.
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