- Nonpeptide Renin Inhibitors Employing a Novel 3-Aza(or oxa)-2,4-dialkyl Glutaric Acid Moiety as a P2/P3 Amide Bond Replacement
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A new series of renin inhibitors has been developed.The inhibitors feature a novel replacement for the P2/P3 dipeptide moiety normally associated with renin inhibitors.The dipeptide replacement was a (2S,4S)-3-aza(or oxa)-2,4-dialkylglutaric acid amide.Ex
- Baker, William R.,Fung, Anthony K. L.,Kleinert, Hollis D.,Stein, Herman H.,Plattner, Jacob J.,et al.
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p. 1722 - 1734
(2007/10/02)
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- Studies on angiotensin converting enzyme inhibitors. V. The diastereoselective synthesis of 2-oxoimidazolidine derivatives
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A diastereoselective synthesis of imidapril (1), which is under clinical study as an antihypertensive drug based on its angiotensin converting enzyme (ACE)-inhibitory activity, was established. N-Alkylation of (2S)-2-amino-4-phenylbutyric acid ester (12) with 3-((2R)-2-methane or toluenesulfonyloxypropionyl)-2-oxoimidazolidine derivative (11) diastereoselectively proceeded in an SN2 fashion to afford tert-butyl (4S)-3-[(2S)-2-[N-[(1S)-1-ethoxycarbonyl)-3-phenylpropyl]amino]propionyl]- 1-methyl-2-oxoimidazolidine-4-carboxylate (13), a precursor of 1. Alternatively, benzyl (2S)-2-[N-(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]propionate (15), which is the key building block of 13, was synthesized by the same strategy. This procedure was also applied to the synthesis of enalapril.
- Kubota,Nunami,Yamagishi,Nishimoto,Hayashi
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p. 1374 - 1377
(2007/10/02)
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- 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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- A Stereoselective Synthesis of N--L-alanine Derivatives by Means of Reductive Amination
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A stereoselective synthesis of N--L-alanine, a portion of the molecule of angiotensin converting-enzyme(ACE) inhibitors, by reductive amination utilizing catecholborane and further applications of the reaction to the synthesis of ACE inhibitors are described.
- Iwasaki, Genji,Kimura, Rieko,Numao, Naganori,Kondo, Kiyoshi
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p. 1691 - 1694
(2007/10/02)
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- Aromatic amino acid derivatives
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A compound having the formula: STR1 wherein n is 0-5, inclusive; R1 is H or the identifying group of an amino acid; and R2 is H, aralkyl, or alkyl.
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- A FAVOURABLE DIASTEREOSELECTIVE SYNTHESIS OF N-(1-S-ETHOXYCARBONYL-3-PHENYLPROPYL)-S-ALANINE
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N-(1-S-Ethoxycarbonyl-3-phenylpropyl)-S-alanine is prepared by Michael addition of S-alaninebenzylester to ethyl-4-oxo-4-phenyl-2-butenoate in a regio- and diastereoselective fashion and subsequent catalytic hydrogenolysis.
- Urbach, H.,Henning, R.
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p. 1143 - 1146
(2007/10/02)
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- 7-Carboxyalkylaminoacyl-1,4-dithia-7-azaspiro[4.4]-nonane-8-carboxylic acids
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This invention relates to 7-carboxyalkyl-aminoacyl-1,4-adithia-7-azaspiro[4.4]nonane-8-carboxylic acids. The compounds of the invention are useful in the treatment of cardiovascular disorders and especially as antihypertensive agents.
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