Irreversible inhibitions of serine proteases by peptidyl allylic halide derivatives

Ohba, Tsuyoshi; Ikeda, Eitatsu; Wakayama, Jun; Takei, Hisashi

doi:10.1016/0960-894x(95)00592-h

Cited by 12 publications

(4 citation statements)

References 15 publications

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“…Thus, the Phe-Phe dipeptidyl a,b-unsaturated ester 17 was prepared by the amidation of N-Boc-phenylalanine with ethyl 4-amino-5-phenyl-2-pentenoate, 23 and then treated with HCl in 1,4-dioxane to remove the Boc group. Thus, the Phe-Phe dipeptidyl a,b-unsaturated ester 17 was prepared by the amidation of N-Boc-phenylalanine with ethyl 4-amino-5-phenyl-2-pentenoate, 23 and then treated with HCl in 1,4-dioxane to remove the Boc group.…”

Section: Design Of Dipeptide Inhibitors Having Double Michael Acceptomentioning

confidence: 99%

“…Ethyl (2E,4S)-4-(tertbutoxycarbonyl)amino-5-phenyl-2-pentenoate 23 was treated with HCl in 1,4-dioxane to remove the Boc group, and the resulting amine was reacted with succinic acid in the presence of EDCI, HOBt, and 4-methylmorpholine, by a procedure similar to that for 17, to give 21a in 80% yield. (1-benzyl-3-ethoxycarbonyl)propenyl]1,4-butanediamide (21a).…”

Section: Dipeptidomimetic Ab-unsaturated Esters 18a-e Thementioning

confidence: 99%

“…23 This assay measures the amount of Formazan produced by metabolic conversion of OwenÕs reagent, [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; MTS], by a dehydrogenase present in the mitochondria of metabolically active cells and is directly proportional to the number of living cells. Cells were later seeded at 7 · 10 4 cells/mL onto a 96-well plate and left overnight before cytotoxicity study.…”

Section: Cytotoxicity Studymentioning

confidence: 99%

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Inhibition of the severe acute respiratory syndrome 3CL protease by peptidomimetic α,β-unsaturated esters

Shie

Fang

Kuo

et al. 2005

Bioorganic & Medicinal Chemistry

102

110

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The proteolytic processing of polyproteins by the 3CL protease of severe acute respiratory syndrome coronavirus is essential for the viral propagation. A series of tripeptide alpha,beta-unsaturated esters and ketomethylene isosteres, including AG7088, are synthesized and assayed to target the 3CL protease. Though AG7088 is inactive (IC50 > 100 microM), the ketomethylene isosteres and tripeptide alpha,beta-unsaturated esters containing both P1 and P2 phenylalanine residues show modest inhibitory activity (IC50 = 11-39 microM). The Phe-Phe dipeptide inhibitors 18a-e are designed on the basis of computer modeling of the enzyme-inhibitor complex. The most potent inhibitor 18c with an inhibition constant of 0.52 microM is obtained by condensation of the Phe-Phe dipeptide alpha,beta-unsaturated ester with 4-(dimethylamino)cinnamic acid. The cell-based assays also indicate that 18c is a nontoxic anti-SARS agent with an EC50 value of 0.18 microM.

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Section: Design Of Dipeptide Inhibitors Having Double Michael Acceptomentioning

confidence: 99%

Section: Dipeptidomimetic Ab-unsaturated Esters 18a-e Thementioning

confidence: 99%

Section: Cytotoxicity Studymentioning

confidence: 99%

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Inhibition of the severe acute respiratory syndrome 3CL protease by peptidomimetic α,β-unsaturated esters

Shie

Fang

Kuo

et al. 2005

Bioorganic & Medicinal Chemistry

102

110

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“…Fluorinated allylamines and α,β-unsaturated fluoralkyl ketones represent an important class of compounds in organic synthesis17a and in medicinal chemistry. 17b, In this context, secondary trifluoromethyl allylamines have been prepared by Lewis acid-catalyzed addition of acetylenes to trifluoroacetaldehyde N , N -aminals,19a by vinylmagnesium bromide addition to N -acyl imines derived from trifluoroacetaldehyde generated in situ,19b or by nucleophilic trifluoromethylation of N -tosyl aldimine,19c while α,β-unsaturated fluoroalkyl ketones have been prepared from esters, 20a,b enamines, 20c-e tellurides,20f or α-acetylenic trifluoromethyl ketones. 20g,h With this in mind, we thought that fluorinated allylamines and unsaturated ketones could be prepared from fluoroalkyl-substituted primary enamino phosphonates 1 .…”

mentioning

confidence: 99%

Fluoroalkyl α,β-Unsaturated Imines. Valuable Synthetic Intermediates from Primary Fluorinated Enamine Phosphonates

et al. 2002

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[reaction: see text] A simple method for the preparation of fluoroalkyl allylamines or alpha,beta-unsaturated ketones by an olefination reaction of primary enamine phosphonates and aldehydes, followed by selective reduction with hydrides or hydrolysis, is reported. Fluorinated beta-amino nitriles are also obtained by an olefination reaction of primary enamine phosphonates with aldehydes and subsequent addition of metalated acetonitrile.

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An Efficient Synthesis ofN-Phosphorylated Azadienes, Primary (E)-Allylamines, and β-Amino-Phosphane Oxides and -Phosphonates from β-Functionalized Oxime Derivatives

et al. 1998

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Irreversible inhibitions of serine proteases by peptidyl allylic halide derivatives

Cited by 12 publications

References 15 publications

Inhibition of the severe acute respiratory syndrome 3CL protease by peptidomimetic α,β-unsaturated esters

Inhibition of the severe acute respiratory syndrome 3CL protease by peptidomimetic α,β-unsaturated esters

Fluoroalkyl α,β-Unsaturated Imines. Valuable Synthetic Intermediates from Primary Fluorinated Enamine Phosphonates

An Efficient Synthesis ofN-Phosphorylated Azadienes, Primary (E)-Allylamines, and β-Amino-Phosphane Oxides and -Phosphonates from β-Functionalized Oxime Derivatives

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