- Studies on the solvent dependence of the carbamic acid formation from ω-(1-naphthyl)alkylamines and carbon dioxide
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Carbamic acid formation from amine and carbon dioxide in a variety of solvents was investigated by measuring NMR (1H, 13C, HMBC) and IR spectra in situ. Bubbling of CO2 through solutions of naphthylalkylamines 1-3 in DMSO, DMF or pyridine (protophilic, highly dipolar, aprotic solvent) resulted in complete conversion of the amines to the corresponding carbamic acids 4-6. In dioxane (protophilic, dipolar, aprotic solvent), the carbamic acid and a small amount of the ammonium carbamate were formed. By contrast, in MeCN (protophobic, dipolar, aprotic solvent), in benzene or CHCl3 (apolar, aprotic solvent), or in 2-PrOH or MeOH (dipolar, amphiprotic solvent), ammonium carbamates 7-9 rather than 4-6 were formed, although the ammonium bicarbonates/carbonates were competitively formed in MeOH. The ammonium carbamates precipitated in many cases and hence they could be separated. The selective generation of the undissociated carbamic acids in preference to the ammonium carbamates in protophilic, dipolar, aprotic solvents (DMSO, DMF, pyridine, and dioxane) is rationalized by considering the acid-base equilibria between the amines 1-3 and the carbamic acids 4-6 in nonaqueous media. The obtained selectivity is likely due to the larger pKa values for 4-6 than the amines 1-3 in these solvents. Interestingly, the fluorescence intensities for 1-3 were dramatically enhanced (4-50 times) in DMSO or DMF upon introduction of CO2, while they were not altered very much in dioxane, MeCN, benzene, CHCl3, 2-PrOH, and MeOH, except small to medium increases (1.3-3 times) for 1 in dioxane, MeCN, 2-PrOH and MeOH. As a whole, the solvent effects observed in these fluorescence studies are consistent with those observed in the above NMR and IR studies. Finally, methoxycarbonylation of amine 3 into the methyl carbamate was successfully accomplished by using (trimethylsilyl)diazomethane in the presence of CO 2. Probably due to pKa(6)>pKa(3) in protophilic dipolar aprotic solvents, the conversion 3→6 is nearly complete while the formation of 9 is minimal.
- Masuda, Koji,Ito, Yoshikatsu,Horiguchi, Masahiro,Fujita, Haruo
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- N1-substituent effects in the selective delivery of polyamine conjugates into cells containing active polyamine transporters
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Several N1-arylalkylpolyamines containing various aromatic ring systems were synthesized as their respective HCl salts. The N 1-substituents evaluated ranged in size from N1-benzyl, N1-naphthalen-1-ylmethyl, Ns
- Gardner, Richard Andrew,Delcros, Jean-Guy,Konate, Fanta,Breitbeil III, Fred,Martin, Bénédicte,Sigman, Michael,Huang, Min,Phanstiel IV, Otto
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- Structure-based design and synthesis of high affinity tripeptide ligands of the Grb2-SH2 domain
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The X-ray structure of the Grb2-SH2 domain in complex with a specific phosphopeptide ligand has revealed the existence of an extended hydrophobic area adjacent to the primary binding site of the ligand on the SH2 domain. This has been exploited to design hydrophobic C-terminal groups that improve the binding affinity of the minimal sequence pTyr-Ile-Asn recognized by the Grb2-SH2 domain. The most significant increase in affinity (25-fold compared to that of the reference peptide having a nonsubstituted carboxamide C- terminus) was obtained with a 3-naphthalen-1-yl-propyl group which was predicted to have the largest contact area with the SH2 domain hydrophobic region. This modification combined with replacement of the minimal sequence isoleucine residue by 1-aminocyclohexane carboxylic acid to stabilize the β- turn conformation required for recognition by the Grb2-SH2 domain resulted in the high affinity (47 nM in an ELISA assay) and selective phosphopeptide Ac- pTyr-Ac6c-Asn-NH(3-naphthalen-1-yl-propyl).
- Furet, Pascal,Gay, Brigitte,Caravatti, Giorgio,García-Echeverría, Carlos,Rahuel, Joseph,Schoepfer, Joseph,Fretz, Heinz
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- NOVEL COMPOUND, PREPARATION METHOD THEREOF, AND USE THEREOF
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The present invention relates to a method for preparing a biomaterial having selectively functionalized tyrosine, a biomaterial having selectively functionalized tyrosine, and a pharmaceutical composition containing the same as an active ingredient. The method for preparing a biomaterial to which a compound represented by formula 2 is coupled, of the present invention, allows the compound represented by formula 2 to be selectively coupled, in a high yield in a biomaterial, to tyrosine, which is present on the surface of an aqueous solution such that the coupling thereof to amino acids other than tyrosine does not occur and, when only one tyrosine is present, heterogeneous mixtures are not present and the inherent activity of the biomaterial is maintained, and thus the compound can be effectively used as a pharmaceutical composition containing a biomaterial drug as an active ingredient. In addition, the method can selectively functionalize tyrosine, and thus can be effectively used for tyrosine functionalization in a biomaterial.
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- A new type of ketolides bearing an N-aryl-alkyl acetamide moiety at the C-9 iminoether synthesis and structure-activity relationships
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A new type of ketolides, bearing an N-aryl-alkyl acetamide moiety at the C-9 iminoether and a cyclic carbonate at the C-11,12 position was prepared and the antibacterial activities of the compounds were evaluated. Some of the derivatives showed potent ant
- Nomura, Takashi,Iwaki, Tsutomu,Yasukata, Tatsuro,Nishi, Koichi,Narukawa, Yukitoshi,Uotani, Koichi,Hori, Toshihiko,Miwa, Hideaki
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p. 6615 - 6628
(2007/10/03)
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- Acylated oligopeptide derivatives having cell signal inhibiting activity
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The invention relates to an acylated peptide, namely a compound of formula (I), wherein n is 0 to 15, X is oxalyl PTI is the bivalent radical of tyrosine or (preferably) the bivalent radical of phosphotyrosine or a phosphotyrosine mimetic, AA stands for a bivalent radical of a natural or unnatural amino acid, and Y is secondary amino group, or a salt thereof, said compound being useful for the treatment of diseases that respond to inhibition of the interaction of (a) protein(s) comprising (an) SH2 domain(s) and a protein tyrosine kinase or a modified version thereof.
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- Design and Synthesis of Naphthalenic Derivatives as Potential Inhibitors of Hydroxyindole-O-methyltransferase
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Hydroxyindole-O-methyltransferase is an enzyme that catalyses the last step of melatonin biosynthesis. The objective of this work was to design and synthesize potential inhibitors of hydroxyindole-O-methyltransferase. Applying bioisosteric principles to the indolic nucleus, we considered the synthesis of naphthalenic derivatives and varied the nature of substituents at position 7 and the amide group. We also replaced the ethylene moiety at position 1 by its lower and higher homologues, and synthesized C4 retroamides. Of the compounds synthesized, N-[2-(7-naphth-1-yl)]phenylacetamide was the best inhibitor of hydroxyindole-O-methyltransferase (77 percent inhibition at a concentration of 10-4 M). Moreover, most of naphthols behaved as enzyme substrates. The ethyl side chain at position 1 was an essential element for optimal biological activity.
- Picard, I. le,Depreux, P.,Lesieur, I.,Delagrange, P.,Bennejean, C.,Renard, P.,Voisin, P.
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p. 183 - 188
(2007/10/03)
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- Potent inhibition of Grb2 SH2 domain binding by non-phosphate- containing ligands
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Development of Grb2 Src homology 2 (SH2) domain binding inhibitors has important implications for treatment of a variety of diseases, including several cancers. In cellular studies, inhibitors of Grb2 SH2 domain binding have to date been large, highly cha
- Yao, Zhu-Jun,King, Richter C.,Cao, Tin,Kelley, James,Milne, George W. A.,Voigt, Johannes H.,Burke Jr., Terrence R.
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