139897-19-1Relevant academic research and scientific papers
Direct intramolecular catalytic enantioselective alkylation of oxazolidinone bromoalkanoate imides
De Rycke, Nicolas,St Denis, Jeffrey D.,Hughes, Jonathan M. E.,Rosadiuk, Kristopher A.,Gleason, James L.
, p. 2802 - 2805 (2014)
Bromoalkanoate imides undergo intramolecular alkylation to form cyclopentane carboximides using catalytic amounts of magnesium bromide in the presence of DBU. Addition of PyBox ligands affords alkylation products with moderate enantioselectivity.
One-pot orthogonal copper-catalyzed synthesis and self-assembly of l-lysine-decorated polymeric dendrimers
Lu, Derong,Hossain, Md. D.,Jia, Zhongfan,Monteiro, Michael J.
, p. 1688 - 1702 (2015)
Synthetic peptides, including cyclic peptides and peptidomimetics, provide stability, protection, and long circulation times compared to free-circulating peptides. Dendritic structures with amino acids or peptides attached to the peripheral layer represent one form of peptidomimetics (i.e., a hybrid peptide/dendrimer construct) that has found use in biological applications. Constructing such dendritic structures from linear polymeric building blocks provides a further advantage of generating a highly ordered and defined structure in the nanoparticle size range. However, the rapid synthesis of such well-defined structures is still a challenge. In this work, we demonstrate that through modulating the copper activity concomitantly of the nitroxide radical coupling (NRC) and the azide-alkyne cycloaddition (CuAAC) reactions, polymeric dendrimers decorated with l-lysine on the periphery could be made rapidly in one pot at 25 °C. Three polymeric dendrimers were constructed with high purity (>94%) and with varying l-lysine density coated on the peripheral generation layer. The self-assembly of these dendrimers in water gave similar sizes to that found in organic solvents, suggesting that the aggregation number of dendritic structures in water was very low and possibly consisting of unimolecular micelles. The findings support the conclusion that the self-assembly of a dendritic architecture in water produces nanoparticles with predictable and well-controlled sizes. This synthetic methodology and the self-assembly properties represent an important step toward synthesizing peptide-decorated dendrimers targeted toward therapeutic applications.
Construction of Janus dendrimers through a self-assembly approach involving chiral discrimination at a focal point
Cole, Ashley M.,Kilway, Kathleen V.,Menuey, Elizabeth M.,Moteki, Shin A.,Zhou, John
supporting information, p. 6404 - 6407 (2021/07/02)
A strategy to build Janus dendrimersviathe chirality-directed self-assembly of heteroleptic Zn(ii) BOX complexes is reported. The method allows quantitative synthesis of Janus dendrimersin situwithout the need for purifications. Each dendritic domain of t
Protein Modification at Tyrosine with Iminoxyl Radicals
Ishiyama, Takashi,Kanai, Motomu,Maruyama, Katsuya,Oisaki, Kounosuke,Sakai, Kentaro,Seki, Yohei,Togo, Takaya
supporting information, p. 19844 - 19855 (2021/11/30)
Post-translational modifications (PTMs) of proteins are a biological mechanism for reversibly controlling protein function. Synthetic protein modifications (SPMs) at specific canonical amino acids can mimic PTMs. However, reversible SPMs at hydrophobic amino acid residues in proteins are especially limited. Here, we report a tyrosine (Tyr)-selective SPM utilizing persistent iminoxyl radicals, which are readily generated from sterically hindered oximes via single-electron oxidation. The reactivity of iminoxyl radicals with Tyr was dependent on the steric and electronic demands of oximes; isopropyl methyl piperidinium oxime 1f formed stable adducts, whereas the reaction of tert-butyl methyl piperidinium oxime 1o was reversible. The difference in reversibility between 1f and 1o, differentiated only by one methyl group, is due to the stability of iminoxyl radicals, which is partly dictated by the bond dissociation energy of oxime O-H groups. The Tyr-selective modifications with 1f and 1o proceeded under physiologically relevant, mild conditions. Specifically, the stable Tyr-modification with 1f introduced functional small molecules, including an azobenzene photoswitch, to proteins. Moreover, masking critical Tyr residues by SPM with 1o, and subsequent deconjugation triggered by the treatment with a thiol, enabled on-demand control of protein functions. We applied this reversible Tyr modification with 1o to alter an enzymatic activity and the binding affinity of a monoclonal antibody with an antigen upon modification/deconjugation. The on-demand ON/OFF switch of protein functions through Tyr-selective and reversible covalent-bond formation will provide unique opportunities in biological research and therapeutics.
METHODS OF TREATMENT WITH AMINOLEVULINIC ACID SYNTHASE 2 (ALAS2) MODULATORS
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Paragraph 00151, (2020/12/29)
Described herein is a compound of Formula I or a pharmaceutically acceptable salt thereof: wherein Ring A R1, R2, a, b, and n are as defined herein. Also described is a method of treating a subject having a disorder in need of treatment, comprising inhibiting aminolevulinic acid synthase 2 (ALAS2) in the subject by administering a compound of Formula (I) or a pharmaceutically acceptable salt thereof. Disorders that are of particular interest are blood disorders, such as porphyria and anemia.
3-(1H-PYRAZOL-4-YL)PYRIDINE ALLOSTERIC MODULATORS OF M4 MUSCARINIC ACETYLCHOLINE RECEPTOR
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Page/Page column 40-41, (2020/05/28)
Provided are cinnolinyl and quinolinyl pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor, compositions comprising said compounds, and uses of said compounds in the treatment or prevention of diseases in which M4 muscarinic acetylcholine receptors are involved, especially neurological and psychiatric disorders and diseases.
Building blocks for recognition-encoded oligoesters that form H-bonded duplexes
Szczypiński, Filip T.,Hunter, Christopher A.
, p. 2444 - 2451 (2019/02/28)
Competition from intramolecular folding is a major challenge in the design of synthetic oligomers that form intermolecular duplexes in a sequence-selective manner. One strategy is to use very rigid backbones that prevent folding, but this design can preju
3-(1H-PYRAZOL-4-YL)PYRIDINE ALLOSTERIC MODULATORS OF THE M4 MUSCARINIC ACETYLCHOLINE RECEPTOR
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Page/Page column 55, (2019/01/16)
The present invention is directed to pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.
INHIBITORS OF RIP1 KINASE AND METHODS OF USE THEREOF
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Paragraph 0327; 0328, (2018/07/04)
The invention provides novel compounds having RIP1 kinase inhibitory activity, pharmaceutical compositions including the compounds and methods of using the compounds.
BICYCLIC AMIDE COMPOUNDS AND METHODS OF USE THEREOF
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Paragraph 0283-0284, (2018/06/15)
The invention provides novel compounds having the general formula I: wherein R1, R2, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds and methods of using the compounds.
