- DPP4 INHIBITOR AND PHARMACEUTICAL APPLICATION THEREOF
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The present invention provides a Dpp4 inhibitor which comprises a leucine derivative of the following formula (1) or a methionine derivative of the following formula (2): wherein each R1 and R3 represents a hydrogen atom (H) and an L-amino acid residue; R2 represents a hydroxyl group (OH), alkoxy group having 1 to 6 carbon atoms, amino group (NH2), alkylamino group having 1 to 6 carbon atoms, glycine residue, β-alanine residue, L-amino acid (except for proline, alanine and phenylalanine) residue or L-amino-acid amide (except for proline amide, alanine amide and phenylalanine amide) residue; and R4 represents a hydroxyl group (OH), alkoxy group having 1 to 6 carbon atoms, amino group (NH2), alkylamino group having 1 to 6 carbon atoms, glycine residue, β-alanine residue, L-amino acid (except for proline and alanine) residue or L-amino-acid amide (except for proline amide and alanine amide) residue. These derivatives also act as autophagy regulators.
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Page/Page column 8-9
(2008/06/13)
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- Synthesis of glutamic acid and glutamine peptides possessing a trifluoromethyl ketone group as SARS-CoV 3CL protease inhibitors
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Trifluoromethyl-β-amino alcohol 11 [(4S)-tert-butyl 4-amino-6,6,6-trifluoro-5-hydroxyhexanoate] was synthesized in five steps starting from Cbz-l-Glu-OH 5 where the key step involved the introduction of the trifluoromethyl (CF3) group to oxazolidinone 7, resulting in the formation of silyl ether 8 [(4S,5S)-benzyl 4-(2-(tert-butoxycarbonyl)ethyl)-5-(trifluoromethyl)-5-(trimethylsilyloxy)oxazolidine-3-carboxylate]. Compound 11 was then converted into four tri- and tetra-glutamic acid and glutamine peptides (1-4) possessing a CF3-ketone group that exhibited inhibitory activity against severe acute respiratory syndrome coronavirus protease (SARS-CoV 3CLpro).
- Sydnes, Magne O.,Hayashi, Yoshio,Sharma, Vinay K.,Hamada, Takashi,Bacha, Usman,Barrila, Jennifer,Freire, Ernesto,Kiso, Yoshiaki
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p. 8601 - 8609
(2007/10/03)
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- The Steric Hindrance of the Stepwise Reaction of N-Carboxy α-Amino Acid Anhydride with the α-Amino Acid Ester
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The mechanisms of the reactions of 4-alkyloxazolidinediones (1) (N-carboxy α-amino acid anhydrides(NCAs)) with α-amino acid benzyl ester p-toluenesulfonates (2) were investigated in acetonitrile containing triethylamine at low and room temperatures.Two types of reactions were observed: (1) the polymerization of NCAs was initiated with a small amount of 2 to produce polypeptides (6), and (2) the dipeptide benzyl esters (4) were produced by the stepwise reaction of NCAs with the esters.Both the polymerization and the dipeptide formation (1+2) seemed to be initiated by the nucleophilic attack of the amino group of the ester on the C-5 carbon of NCAs.The polymerization proceeded when the side chains of the amino acid esters (R2) were more bulky than those of the NCAs (R1).On the contrary, dipeptide esters were produced when the side chains of the NCAs (R1) were more bulky than those of the esters (R2).
- Oya, Masanao,Takahashi, Tomoko
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p. 2705 - 2707
(2007/10/02)
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