845269-67-2Relevant articles and documents
FUNCTIONALIZED HETEROCYCLIC COMPOUNDS AS MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)
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, (2021/06/22)
The present invention relates to compound-linker constructs and antibody-drug-conjugates of compounds of formula (I) that are useful as modulators of STING (Stimulator of Interferon Genes).
HETEROCYCLIC COMPOUNDS AS MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)
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Page/Page column 135-137, (2021/06/22)
The present invention relates to compounds of formula (I) and salts, stereoisomers, tautomers or N-oxides thereof that are useful as modulators of STING (Stimulator of Interferon Genes). The present invention further relates to the compounds of formula (I) for use as a medicament and to a pharmaceutical composition comprising said compounds.
On the Virtue of Indium in Reduction Reactions. A Comparison of Reductions Mediated by Indium and Zinc: Is Indium Metal an Effective Catalyst for Zinc Induced Reductions?
Matassini, Camilla,Bonanni, Marco,Marradi, Marco,Cicchi, Stefano,Goti, Andrea
supporting information, p. 1106 - 1113 (2019/12/24)
Indium(0)-mediated reductions have been reported for the transformation of several functional groups (imines, oximes, nitro groups, isoxazolidines, and conjugated alkenes, among others), prompted by the opportunity of performing the reactions in aqueous media and green conditions. We describe here the comparison of several reactions using indium or the less expensive zinc, carried out in order to evaluate the effective advantages brought about indium metal. We found some reactions for which use of In is mandatory and others where Zn worked equally well or even better. The reduction of hydroxylamines to the corresponding amines was the only reduction for which use of In provided much better results than Zn and was also possible to apply an efficient catalytic version with use of 2–5 mol-% In in the presence of stoichiometric Zn. Applicability of this catalytic reduction to “one-pot” model processes is also demonstrated.
Synthesis of N-Substituted Iminosugar Derivatives and Evaluation of Their Immunosuppressive Activities
Lv, Zhuo,Song, Chengcheng,Niu, Youhong,Li, Qin,Ye, Xin-Shan
, p. 338 - 351 (2018/02/27)
It is important to find more effective and safer immunosuppressants, because clinically used immunosuppressive agents have significant side effects. A series of N-substituted iminosugar derivatives were designed and synthesized, and their immunosuppressive effects were evaluated by the CCK-8 assay. The results revealed that iminosugars 10 e and 10 i, that is, (3R,4S)-1-(4-heptyloxylphenylethyl)pyrrolidine-3,4-diol and (3R,4S)-1-[2-(2-chloro-4-(p-tolylthio)-phenyl-1-yl)ethyl]pyrrolidine-3,4-diol, respectively, exhibited the strongest inhibitory effects on mouse splenocyte proliferation (IC50=2.16 and 2.48 μm, respectively), whereas the iminosugars containing an amide group near the hydrophilic head (compounds 10 j–n) exhibited no inhibitory effects. Further studies revealed that the inhibitory effects on splenocyte proliferation may have come from the suppression of both IFN-γ and IL-4 cytokines. Our results suggest that synthetic iminosugars, especially compounds 10 e and 10 i, hold potential as immunosuppressive agents.
IBX-mediated oxidation of unactivated cyclic amines: application in highly diastereoselective oxidative Ugi-type and aza-Friedel-Crafts reactions
De Graaff,Bensch,Van Lint, Matthijs J.,Ruijter,Orru
supporting information, p. 10108 - 10112 (2015/10/20)
The first o-iodoxybenzoic acid (IBX) mediated oxidation of unactivated amines to imines is described. A range of meso-pyrrolidines were shown to be suitable substrates. The chemical space was further explored with one-pot oxidative Ugi-type and aza-Friedel-Crafts reactions, which proved to be highly diastereoselective.
COFERONS AND METHODS OF MAKING AND USING THEM
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Page/Page column 241, (2012/12/13)
The present invention is directed to a monomer useful in preparing therapeutic compounds. The monomer includes one or more pharmacophores which potentially binds to a target molecule with a dissociation constant of less than 300 μM and a linker element connected to the pharmacophore. The linker element has a molecular weight less than 500 daltons, is connected, directly or indirectly through a connector, to the pharmacophore.
A methodology for simultaneous fluorogenic derivatization and boronate affinity enrichment of 3-nitrotyrosine-containing peptides
Dremina, Elena S.,Li, Xiaobao,Galeva, Nadezhda A.,Sharov, Victor S.,Stobaugh, John F.,Schoeneich, Christian
, p. 184 - 196 (2012/05/19)
We synthesized and characterized a new tagging reagent, (3R,4S)-1-(4-(aminomethyl)phenylsulfonyl)pyrrolidine-3,4-diol (APPD), for the selective fluorogenic derivatization of 3-nitrotyrosine (3-NT) residues in peptides (after reduction to 3-aminotyrosine) and affinity enrichment. The synthetic 3-NT-containing peptide, FSAY(3-NO2)LER, was employed as a model for method validation. Furthermore, this derivatization protocol was successfully tested for analysis of 3-NT-containing proteins exposed to peroxynitrite in the total protein lysate of cultured C2C12 cells. The quantitation of 3-NT content in samples was achieved through either fluorescence spectrometry or boronate affinity chromatography with detection by specific fluorescence (excitation and emission wavelengths of 360 and 510 nm, respectively); the respective limits of detection were 95 and 68 nM (19 and 13 pmol total amount) of 3-NT. Importantly, the derivatized peptides show a strong retention on a synthetic boronate affinity column, containing sulfonamide-phenylboronic acid, under mild chromatographic conditions, affording a route to separate the derivatized peptides from large amounts (milligrams) of nonderivatized peptides and to enrich them for fluorescent detection and mass spectrometry (MS) identification. Tandem MS analysis identified chemical structures of peptide 3-NT fluorescent derivatives and revealed that the fluorescent derivatives undergo efficient backbone fragmentations, permitting sequence-specific identification of protein nitration at low concentrations of 3-NT in complex protein mixtures. Copyright
Protein tagging reagents
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, (2008/12/05)
Benzylamine-like reagents for the affinity enrichment and relative quantification of post-translational hydroxylation and nitration of tyrosine and tryptophan in proteins are provided.
Use of DOE for rapid development of a red-Al reduction process for the synthesis of 3,4-isopropylidenedioxypyrrolidine hydrotosylate
Alimardanov, Asaf R.,Barrila, Mark T.,Busch, Frank R.,Carey, James J.,Couturier, Michel A.,Cui, Curtis
, p. 834 - 837 (2013/09/03)
Statistical design of experiments (DOE) was used to rapidly optimize Red-Al reduction of an imide to produce, after deprotection and salt formation, 3,4-isopropylidenedioxypyr-rolidine hydrotosylate (1), an intermediate in the synthesis of Ingliforib. A Red-Al reduction process was successfully scaled to produce multikilogram quantities of 1, thus demonstrating a safer and more economical process. Further development resulted in an optimized procedure, which not only avoided borane reduction but also allowed the three-step procedure to be performed without isolation of the intermediates, solvent exchange, or distillation.
Highly diastereoselective additions to polyhydroxylated pyrrolidine cyclic imines: Ready elaboration of aza-sugar scaffolds to create diverse carbohydrate-processing enzyme probes
Chapman, Timothy M.,Courtney, Steve,Hay, Phil,Davis, Benjamin G.
, p. 3397 - 3414 (2007/10/03)
Representative diastereomeric, erythritol and threitol polyhydroxylated pyrrolidine imine scaffolds have been rapidly elaborated to diversely functionalized aza-sugars through highly diastereoselective organometallic (RM) additions (R = Me, Et, allyl, hex
