- Studies on Angiotensin Converting Enzyme Inhibitors. 4. Synthesis and Angiotensin Converting Enzyme Inhibitory Activities of 3-Acyl-1-alkyl-2-oxoimidazolidine-4-carboxylic Acid Derivatives
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(4S)-1-Alkyl-3-acyl>-2-oxoimidazolidine-4-carboxylic acid derivatives (3) were prepared by two methods.Their angiotensin converting enzyme (ACE) inhibitory activities and antihypertensive effects were evaluated, and the structure-activity relationships were discussed.The dicarboxylic acids 3a-n possessing S,S,S configuration showed potent in vitro ACE inhibitory activities with IC 50 values of 1.1x10-8-1.5x10-9 M.The most potent compound in this series, monoester 3p, had an ID 50 value of 0.24 mg/kg, po for inhibition of angiotensin I induced pressor response in normotensive rats and produced a dose-dependent decrease in systolic blood pressure of spontaneously hypertensive rats (SHRs) at doses of 1-10 mg/kg, po.
- Hayashi, Kimiaki,Nunami, Ken-ichi,Kato, Jyoji,Yoneda, Naoto,Kubo, Masami,et al.
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p. 289 - 297
(2007/10/02)
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- ON THE CATALYTIC AMIDOCARBONYLATION OF SUBSTITUTED ALLYLIC ALCOHOLS
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Substituted allylic alcohols (3-methyl-2-buten-1-ol and 2-methyl-3-buten-2-ol) were isomerized and amidocarbonylated.In addition to the expected product, N-acetylleucine, arising from their rearrengement to 3-methylbutanal and subsequent amidocarbonylation (22percent yield), we isolated two additional products (28percent yield).These were shown by spectroscopic methods and by syntheses, via amidocarbonylations of the respective aldehydes, to be 2-acetamido-5-methylhexanoic acid and 2-acetamido-4-methylhexanoic acid.Their formation is postulated to be the sequential result of (i) dehydration first to form isoprene, (ii) hydroformylation and hydrogenation of isoprene to give 3-methyl-1-pentanal and 4-methyl-1-pentanal, and (iii) aldehyde amidocarbonylation.Treatment of isoprene itself under the same conditions also gave these latter two acetylamino acids.
- Yuan, Sun-Shine,Ajami, Alfred M.
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p. 255 - 258
(2007/10/02)
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