- Trimethyl-substituted carbamate as a versatile self-immolative linker for fluorescence detection of enzyme reactions
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Self-immolative linker is a useful building block of molecular probes, with broad applications in the fields of enzyme activity analysis, stimuli-responsive material science, and drug delivery. This manuscript presents N-methyl dimethyl methyl (i.e., trimethyl) carbamate as a new class of self-immolative linker for the fluorescence detection of enzyme reactions. The trimethyl carbamate was shown to spontaneously undergo intramolecular cyclization upon formation of a carboxylate group, to liberate a fluorophore with the second time rapid reaction kinetics. Interestingly, the auto-cleavage reaction of trimethyl carbamate was also induced by the formation of hydroxyl and amino groups. Fluorescent probes with a trimethyl carbamate could be applicable for fluorescence monitoring of the enzyme reactions catalyzed by esterase, ketoreductase, and aminotransferase, and for fluorescence imaging of intracellular esterase activity in living cells, hence demonstrating the utility of this new class of self-immolative linker.
- Inoue, Kazuya,Nakamura, Noriaki,Ojida, Akio,Uchinomiya, Shohei
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supporting information
(2020/05/25)
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- Total synthesis method for xinaomycin
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The invention belongs to the technical field of pharmaceutical chemistry and organic synthesis, and aims to provide a chemical total synthesis method for xinaomycin. The method comprises the steps of:using D-galactose and the like as raw materials, firstly carrying out 8 steps of reactions to obtain a compound 14, then performing condensation on the compound 14 and uracil to obtain a compound 15,performing 4 steps of reactions to obtain a compound 19, performing condensation on the compound 19 and a compound 6 to obtain a compound 20, and finally removing an ester protecting group and a Cbzprotecting group in turn, so as to obtain the natural product xinaomycin. The total synthesis method of the present invention is a method for synthesizing the natural product xinaomycin for the firsttime. The total synthesis method has the advantages of high product purity, low cost, simple operation and the like.
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Paragraph 0033; 0053; 0055; 0056
(2018/05/16)
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- Toward the selective delivery of chemotherapeutics into tumor cells by targeting peptide transporters: Tailored gold-based anticancer peptidomimetics
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Complexes [AuIIIX2(dtc-Sar-AA-O(t-Bu))] (AA = Gly, X = Br (1)/Cl (2); AA = Aib, X = Br (3)/Cl (4); AA = l-Phe, X = Br (5)/Cl (6)) were designed on purpose in order to obtain gold(III)-based anticancer peptidomimetics that might specifically target two peptide transporters (namely, PEPT1 and PEPT2) upregulated in several tumor cells. All the compounds were characterized by means of FT-IR and mono- and multidimensional NMR spectroscopy, and the crystal structure of [AuIIIBr2(dtc-Sar-Aib-O(t- Bu))] (3) was solved and refined. According to in vitro cytotoxicity studies, the Aib-containing complexes 3 and 4 turned out to be the most effective toward all the human tumor cell lines evaluated (PC3, DU145, 2008, C13, and L540), reporting IC50 values much lower than that of cisplatin. Remarkably, they showed no cross-resistance with cisplatin itself and were proved to inhibit tumor cell proliferation by inducing either apoptosis or late apoptosis/necrosis depending on the cell lines. Biological results are here reported and discussed in terms of the structure-activity relationship.
- Negom Kouodom, Morelle,Ronconi, Luca,Celegato, Marta,Nardon, Chiara,Marchiò, Luciano,Dou, Q. Ping,Aldinucci, Donatella,Formaggio, Fernando,Fregona, Dolores
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supporting information; scheme or table
p. 2212 - 2226
(2012/05/05)
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- Rational design of gold(III)-dithiocarbamato peptidomimetics for the targeted anticancer chemotherapy
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As a further extension of our research work focusing on the development of gold(III)-dithiocarbamato dtc derivatives of oligopeptides as potential anticancer agents, complexes [AuIIIX2(dtc-Sar-l-Ser(t-Bu)- O(t-Bu))] (X = Br (1a)/Cl (
- Kouodom, Morelle Negom,Boscutti, Giulia,Celegato, Marta,Crisma, Marco,Sitran, Sergio,Aldinucci, Donatella,Formaggio, Fernando,Ronconi, Luca,Fregona, Dolores
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p. 248 - 260
(2013/01/15)
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- CYCLOHEXYL-AZETIDINYL ANTAGONISTS OF CCR2
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The present invention comprises compounds of Formula (I). Wherein: R1, R2, R4, J, Q, and A are as defined in the specification. The invention also comprises a method of preventing, treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is type II diabetes, obesity and asthma. The invention also comprises a method of inhibiting CCR2 activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula (I).
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Page/Page column 136
(2012/01/06)
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- Effective methods for the synthesis of N-methyl β-amino acids from all twenty common α-amino acids using 1,3-oxazolidin-5-ones and 1,3-oxazinan-6-ones
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N-Methyl β-amino acids are generally required for application in the synthesis of potentially bioactive modified peptides and other oligomers. Previous work highlighted the reductive cleavage of 1,3-oxazolidin-5-ones to synthesise N-methyl α-amino acids. Starting from α-amino acids, two approaches were used to prepare the corresponding N-methyl β-amino acids. First, α-amino acids were converted to N-methyl α-amino acids by the so-called '1,3-oxazolidin-5-one strategy', and these were then homologated by the Arndt-Eistert procedure to afford N-protected N-methyl β-amino acids derived from the 20 common α-amino acids. These compounds were prepared in yields of 23-57% (relative to N-methyl α-amino acid). In a second approach, twelve N-protected α-amino acids could be directly homologated by the Arndt-Eistert procedure, and the resulting β-amino acids were converted to the 1,3-oxazinan-6-ones in 30-45% yield. Finally, reductive cleavage afforded the desired N-methyl β-amino acids in 41-63% yield. One sterically congested β-amino acid, 3-methyl-3-aminobutanoic acid, did give a high yield (95%) of the 1,3-oxazinan-6-one (65), and subsequent reductive cleavage gave the corresponding AIBN-derived N-methyl β-amino acid 61 in 71% yield (Scheme 2). Thus, our protocols allow the ready preparation of all N-methyl β-amino acids derived from the 20 proteinogenic α-amino acids.
- Hughes, Andrew B.,Sleebs, Brad E.
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p. 2611 - 2637
(2007/10/03)
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- Synthesis and pharmacological evaluation of glycine-modified analogues of the neuroprotective agent glycyl-L-prolyl-L-glutamic acid (GPE)
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The synthesis of 10 G*PE analogues, wherein the glycine residue has been modified, is described by coupling readily accessible dibenzyl-l-prolyl-l- glutamate 2 with various analogues of glycine. Pharmacological evaluation of the novel compounds was undertaken to further understand the role of the glycine residue on the observed neuroprotective properties of the endogenous tripeptide GPE.
- Lai, Michelle Y.H.,Brimble, Margaret A.,Callis, David J.,Harris, Paul W.R.,Levi, Mark S.,Sieg, Frank
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p. 533 - 548
(2007/10/03)
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- Pyrrolidine derivatives
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The present invention relates to pyrrolidine derivatives and dimeric forms and/or pharmaceutically acceptable esters, and/or salts thereof. The compounds are useful as inhibitors of metalloproteases, e.g. zinc proteases, particularly zinc hydrolases, and which are effective in treating disease states are associated with vasoconstriction of increasing occurrences.
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- A novel concept in combinatorial chemistry in solution with the advantages of solid-phase synthesis: Formation of N-betaines by multicomponent domino reactions
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Advantages of solid-phase and liquid-phase synthesis are combined in a new concept of combinatorial chemistry: a domino sequence comprising Knoevenagel and hetero-Diels-Alder reactions, with subsequent hydrogenation starting from protected aminoaldehydes, 1.3-dicarbonyl compounds, and enol ethers leads to N-heterocycles of high diversity with a betaine structure, which are isolated in highly pure form by precipitation with diethyl ether (see scheme), Cbz = benzylocycarbonyl, Bn = benzyl.
- Tietze, Lutz F.
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p. 903 - 905
(2007/10/03)
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- Highly efficient synthesis of sterically hindered peptides containing N-methylated amino acid residues using a novel 1H-benzimidazolium salt
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Novel 1H-benzimidazolium type peptide coupling reagent, CMBI, was designed, synthesized, and shown to be efficient in the promotion of the formation of sterically hindered amide and ester bonds. Its high efficiency was proved by model reaction tests and the successful synthesis of various hindered oligopeptides and peptide segments containing N-methyl amino acid residues with fast reaction speeds, low racemization and excellent yields. A mechanism for amide bond formation mediated by the reagent was proposed. (C) 2000 Elsevier Science Ltd.
- Li, Peng,Xu, Jie Cheng
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p. 9949 - 9955
(2007/10/03)
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- The design, synthesis, and biological evaluation of analogues of the serine-threonine protein phosphatase 1 and 2A selective inhibitor microcystin LA: Rational modifications imparting PP1 selectivity
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Based on the results from previously reported molecular modeling analyses of the interactions between the inhibitor microcystin and the serine-threonine protein phosphatases 1 and 2A, we have designed analogues of microcystin LA with structural modifications intended to impart PP1 selectivity. The synthesis of several first generation analogues followed by inhibition assays revealed that all three are PP1-selective, as predicted. Although the observed selectivities are modest, one of the designed analogues is more selective for PP1 than any known small molecule inhibitor. Copyright (C) 1999 Elsevier Science Ltd.
- Aggen, James B.,Humphrey, John M.,Gauss, Carla-Maria,Huang, Hsien-Bin,Nairn, Angus C.,Chamberlin, A. Richard
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p. 543 - 564
(2007/10/03)
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- Folate-based inhibitors of thymidylate synthase: Synthesis and antitumor activity of γ-linked sterically hindered dipeptide analogues of 2-desamino- 2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583)
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In an effort to synthesize inhibitors of thymidylate synthase (TS) that do not undergo polyglutamation, a series of γ-linked sterically hindered dipeptide analogues of 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583) was pre
- Bavetsias, Vassilios,Jackman, Ann L.,Marriott, Jonathan H.,Kimbell, Rosemary,Gibson, William,Boyle, F. Thomas,Bisset, Graham M. F.
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p. 1495 - 1510
(2007/10/03)
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- Thymidylate synthase inhibiting quinazolinones
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Quinazolines of the formula STR1 wherein R1 is typically methyl, hydrogen or amino; R2 is typically methyl or propargyl; Ar is typically phenylene or 2'-fluorophenylene; R3 is the residue of a dipeptide substituted, typically by methyl, at position (a), (b) or (c), shown in the following partial formula: STR2 R4, R5, R6 and R8 are typically hydrogen, R7 is typically hydrogen or methyl; or a pharmaceutically acceptable salt, ester or amide thereof are of value in the treatment of cancer.
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- Synthesis of N-Benzyloxycarbonyl-N-methylaminoacids from Oxazolidine-5-one Derivatives
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Hydrogenolysis of 3-benzyloxycarbonyloxazolidine-5-one and 3-benzyloxycarbonyl-4-benzyloxazolidine-5-one by Et3SiH in the presence of F3CCO2H is demonstrated to be a convenient method for preparing substituted N-methylaminoacids.In contrast with catalytic
- Chipens, G. I.,Slavinskaya, V. A.,Sile, D. E.,Korchagova, E. Kh.,Katkevich, M. Yu.,Grigor'eva, V. D.
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p. 576 - 578
(2007/10/02)
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- Asymmetric Synthesis of Calyculin A. 2. The C26-C37 γ-Amino Acid Fragments
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New chiral imide enolate alkylation, aldol, and Michael addition bond constructions have been employed in the asymmetric synthesis of the C26-C37 portion of calyculin A.
- Evans, David A.,Gage, James R.,Leighton, James L.,Kim, Annette S.
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p. 1961 - 1963
(2007/10/02)
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- CHIRAL LIGANDS CONTAINING HETEROATOMS. II. MODIFIED LITHIUM ALUMINIUM HYDRIDE REAGENTS FROM CHIRAL 1,2-DIAMINOETHANES
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Procedures for the preparation of N-methyl-N'--1,2-diaminoethane, N-methyl-N'--1,2-diaminoethane and (S)-N-methyl-N'-phenyl-1-isopropyl-1,2-diaminoethane are reported.The stereochemistry of the products obtained by amine-m
- Falorni, Massimo,Lardicci, Luciano,Giacomelli, Giampaolo
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p. 573 - 576
(2007/10/02)
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- Anti-allergic compositions and their use
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Pharmaceutical compositions are described for anti-allergy therapy comprising an allergen or allergen extract, polysarcosine having an average molecular weight in the range of 2,000 to 12,000 and a chemical linking group connecting a reactive site on the polysarcosine to an amino group on the allergen or allergen extract, the reactive site on the polysarcosine being a H(CH3)N--, the allergen extract being an extract from an allergen selected from pollens, weeds, house dust mites and venoms, and the chemical linking group having the formula --CO--B--CO where B is a hydrocarbon chain of 1-4 carbon atoms. The disclosure also describes the analogous conjugates.
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- Chiral, N-protected, N-substituted α-amino acids
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Chiral N-protected, N-substituted α-amino acids are described. These compounds are prepared by condensation of an N-protected α-amino acid with an aldehyde followed by the selective reductive cleavage of an oxazolidinone intermediate.
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- HYDROXY SUBSTITUTED PEPTIDE COMPOUNDS
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Hydroxy substituted peptide compounds of the formula STR1 are disclosed. These compounds are useful as hypotensive agents due to their angiotensin converting enzyme inhibition activity and depending upon the definition of X may also be useful as analgesics due to their enkephalinase inhibition activity.
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- Aqueous Solutions Containing Amino Acids and Peptides. Part 19: The Enthalpic Coefficients for the Interactions of N-Acetylsarcosinamide with 2-(N-acetylamino)acyl Amides at 25 deg C
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Enthalpies of dilution both of solutions of N-acetylsarcosinamide and of ternary solutions equimolal in N-acetylsarcosinamide and N-acetylglycinamide, N-acetyl-L-alaninamide, N-acetyl-L-valinamide or N-acetyl-L-leucinamide have been determined by a microc
- Blackburn, G. M.,Lilley, T. H.,Milburn, P. J.
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p. 789 - 804
(2007/10/02)
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- Acyl derivatives
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Peptide derivatives provided by the present invention are compounds of the general formula STR1 wherein R1 represents a hydrogen atom or the methyl or hydroxymethyl group or a mono-, di- or trihalomethyl mgroup; R2 represents the cha
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- Method and composition for preparation of H-SAR-LYS-SAR-GLN-NH2
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A method for solution synthesis of H-SAR-LYS-SAR-GLN-NH2 in good yield and compositions useful therein are disclosed.
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