- GADD45BETA TARGETING AGENTS
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Compounds based around tetrapeptide, tripeptide and dipeptide moeties and corresponding peptiod moeties. Related methods and pharmaceutical compositions for use in treatment of cancer, inflammatory diseases, and other disorders.
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- NOVEL IMIDAZOLIDINONE DERIVATIVE, METHOD OF PRODUCING THE SAME AND METHOD OF PRODUCING OPTICALLY ACTIVE AMINO ACID
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The objective of the present invention is to provide an optically active imidazolidinone derivative widely usable for synthesizing an optically active amino acid, a method of easily producing the derivative, and a method of easily producing an optically active amino acid by using the derivative. The objective can be achieved by producing an optically active amino acid using a novel optically active imidazolidinone derivative represented by a general formula (3) and the like. According to the method of the present invention, an optically active imidazolidinone derivative can be obtained by preferential crystallization from a mixture of isomers of the imidazolidinone derivative. Therefore, an optically active amino acid can be easily and stereoselectively produced without cumbersome procedures required for the conventional methods, such as resolution of diastereomers, synthesis from an optically active amino acid and resolution of isomers by silica gel column cromatography.
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Page/Page column 39-40
(2009/05/29)
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- Production method of optically active diphenylalanine compounds
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The present invention provides a production method including reacting a diphenylmethylene halide compound represented by the following formula (1) with a malonic acid diester compound represented by the following formula (2) in an organic solvent selected
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Page/Page column 22
(2008/06/13)
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- Synthesis of both enantiomers of β,β-diphenyl-α-alanine (Dip) from glycine using (S)- or (R)-2-[(N-benzylprolyl)amino] benzophenone as a reusable chiral auxiliary
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Preparative syntheses of enantiopure (S)- and (R)-Dip by α-C-alkylation with Ph2CHX (X=Cl or Br) of the glycine moiety in a Ni(II) Schiff's base complex 1 derived from glycine and (S)- or (R)-[(N-benzylprolyl)amino]benzophenone (BPB) is described. The diastereoselectivity of the alkylation with PhCH2Br in DMF in the presence of NaOH is both kinetically and thermodynamically controlled.
- Tararov, Vitali I.,Savel'eva, Tatyana F.,Kuznetsov, Nickolai Yu.,Ikonnikov, Nikolai S.,Orlova, Svetlana A.,Belokon', Yuri N.,North, Michael
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- Design and Synthesis of Side-Chain Conformationally Restricted Phenylalanines and Their Use for Structure-Activity Studies on Tachykinin NK-1 Receptor
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Constrained analogues of phenylalanine have been conceptually designed for analyzing the binding pockets of Phe7 (S7) and Phe8 (S8), two aromatic residues important for the pharmacological properties of SP, i.e., L-tetrahydroisoquinoleic acid, L-diphenylalanine, L-9-fluorenylglycine (Flg), 2-indanylglycine, the diastreomers of L-1-indanylglycine (Ing) and L-1-benzindanylglycine (Bfi), and the Z and E isomers of dehydrophenylalanine (ΔZPhe, ΔEPhe).Binding studies were performed with appropriate ligands and tissue preparations allowing the discrimination of the three tachykinin binding sites, NK-1, NK-2, and NK-3.The potencies of these agonists were evaluated in the guinea pig ileum bioassay.According to the binding data, we can conclude that the S7 subsite is small, only the gauche(-) probe 7>SP presents a high affinity for specific NK-1 binding sites.Surprisingly, the EPhe7>SP analogue, which projects the aromatic ring toward the trans orientation, is over 40-fold more potent than the Z isomer, ZPhe7>SP.A plausible explanation of these conflictual results is that either the binding protein quenches the minor trans rotamer of 7>SP in solution or this constrained amino acid side chain rotates when inserted in the protein.In position 8, the high binding affinities of 8>SP and 8>SP suggest that the S8 subsite is large enough to accept two aromatic rings in the gauche(-) and one aromatic ring in the trans direction.Peptides bearing two conformational probes in positions 7, 8 or 9 led to postulate that S7, S8, and S9 subsites are independent from each other.The volumes available for side chains 7 and 8 can be estimated to be close to 110 and 240 Angstroem3, respectively.The large volume of the S8 subsite raises question on the localization of the SP-binding site in the NK-1 receptor.If SP were to bind in the transmembrane domains, the cleft defined by the seven transmembrane segments must rearrange during the binding process in order to bind a peptide in an α-helical structure and at least one large binding subsite in position 8.Thus, indirect topographical analysis with constrained amino acids might contribute to the analysis of the receptor/ligand dynamics.Finally, this study demonstrates that a good knowledge of the peptidic backbone structure and a combination of constrained amino acids are prerequisites to confidently attribute the preferred orientation(s) of an amino acid side chain.
- Josien, Hubert,Lavielle, Solange,Brunissen, Alie,Saffroy, Monique,Torrens, Yvette,et al.
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p. 1586 - 1601
(2007/10/02)
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- Process for the preparation of D(-) and L(+)-3,3-diphenylalanine and D(-) and L(+)-substituted 3,3-diphenylalanines and derivatives thereof
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A process for the preparation of D(-) and L(+)-3,3-diphenylalanine and D(-) and L(+)-substituted 3,3-diphenylalanines is described where N-protected DL-3,3-diphenylalanine or N-protected-DL-substituted 3,3-diphenylalanine are treated with (-)cinchonidine and the resulting salt resolved into the desired enantiomers, as well as derivatives thereof and valuable intermediates used in the process.
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