54751-01-8Relevant academic research and scientific papers
Substituted dienes prepared from betulinic acid – Synthesis, cytotoxicity, mechanism of action, and pharmacological parameters
Frydrych, Ivo,Urban, Milan,?arek, Jan,Benická, Sandra,D?ubák, Petr,Gurská, Soňa,Hajdúch, Marián,Kotulová, Jana,Li?ková, Barbora,Olejníková, Denisa,Pokorny, Jan
, (2021/07/28)
A set of new substituted dienes were synthesized from betulinic acid by its oxidation to 30-oxobetulinic acid followed by the Wittig reaction. Cytotoxicity of all compounds was tested in vitro in eight cancer cell lines and two noncancer fibroblasts. Almost all dienes were more cytotoxic than betulinic acid. Compounds 4.22, 4.30, 4.33, 4.39 had IC50 below 5 μmol/L; 4.22 and 4.39 were selected for studies of the mechanism of action. Cell cycle analysis revealed an increase in the number of apoptotic cells at 5 × IC50 concentration, where activation of irreversible changes leading to cell death can be expected. Both 4.22 and 4.39 led to the accumulation of cells in the G0/G1 phase with partial inhibition of DNA/RNA synthesis at 1 × IC50 and almost complete inhibition at 5 × IC50. Interestingly, compound 4.39 at 5 × IC50 caused the accumulation of cells in the S phase. Higher concentrations of tested drugs probably inhibit more off-targets than lower concentrations. Mechanisms disrupting cellular metabolism can induce the accumulation of cells in the S phase. Both compounds 4.22 and 4.39 trigger selective apoptosis in cancer cells via intrinsic pathway, which we have demonstrated by changes in the expression of the crucial apoptosis-related protein. Pharmacological parameters of derivative 4.22 were superior to 4.39, therefore 4.22 was the finally selected candidate for the development of anticancer drug.
Synthesis and Biological Evaluation of Hapten-Clicked Analogues of The Antigenic Peptide Melan-A/MART-126(27L)-35
Tarbe, Marion,Miles, John J.,Edwards, Emily S. J.,Miles, Kim M.,Sewell, Andrew K.,Baker, Brian M.,Quideau, Stéphane
supporting information, p. 799 - 807 (2020/04/20)
A click-chemistry-based approach was implemented to prepare peptidomimetics designed in silico and made from aromatic azides and a propargylated GIGI-mimicking platform derived from the altered Melan-A/MART-126(27L)-35 antigenic peptide ELAGIGILTV. The CuI-catalyzed Huisgen cycloaddition was carried out on solid support to generate rapidly a first series of peptidomimetics, which were evaluated for their capacity to dock at the interface between the major histocompatibility complex class-I (MHC-I) human leucocyte antigen (HLA)-A2 and T-cell receptors (TCRs). Despite being a weak HLA-A2 ligand, one of these 11 first synthetic compounds bearing a p-nitrobenzyl-triazole side chain was recognized by the receptor proteins of Melan-A/MART-1-specific T-cells. After modification of the N and C termini of this agonist, which was intended to enhance HLA-A2 binding, one of the resulting seven additional compounds triggered significant T-cell responses. Thus, these results highlight the capacity of naturally circulating human TCRs that are specific for the native Melan-A/MART-126-35 peptide to cross-react with peptidomimetics bearing organic motifs structurally different from the native central amino acids.
4-methoxymethylpyridine synthesis method
-
Paragraph 0023; 0024; 0028; 0029; 0030; 0033; 0034, (2020/02/04)
The invention relates to the field of organic chemistry, particularly to a 4-methoxymethylpyridine synthesis method, which comprises: carrying out a bromination reaction on 4-methylpyridine as a raw material to obtain 4-bromo-methylpyridine; carrying out a reaction on the 4-bromo-methylpyridine and trimethylamine to obtain (4-pyridylmethyl)trimethyl ammonium bromide; and dissolving the (4-pyridylmethyl)trimethyl ammonium bromide in methanol, adding sodium methoxide, and carrying out heating reflux for 1 h in the presence of nitrogen to obtain the 4-methoxymethylpyridine. According to the invention, by using the synthesis method, 4-methylpyridine is used as the raw material, and is subjected to the bromination reaction to obtain 4-bromo-methylpyridine, the 4-bromo-methylpyridine reacts withtrimethylamine to obtain (4-pyridylmethyl)trimethyl ammonium bromide, and finally the (4-pyridylmethyl)trimethyl ammonium bromide reacts with sodium methoxide to obtain the 4-methoxymethylpyridine; and the synthesis method is high in total yield, cheap in raw material price, short in reaction time, mild in condition and simple in process operation.
Spin-Center Shift-Enabled Direct Enantioselective α-Benzylation of Aldehydes with Alcohols
Nacsa, Eric D.,MacMillan, David W. C.
supporting information, p. 3322 - 3330 (2018/03/13)
Nature routinely engages alcohols as leaving groups, as DNA biosynthesis relies on the removal of water from ribonucleoside diphosphates by a radical-mediated "spin-center shift" (SCS) mechanism. Alcohols, however, remain underused as alkylating agents in synthetic chemistry due to their low reactivity in two-electron pathways. We report herein an enantioselective α-benzylation of aldehydes using alcohols as alkylating agents based on the mechanistic principle of spin-center shift. This strategy harnesses the dual activation modes of photoredox and organocatalysis, engaging the alcohol by SCS and capturing the resulting benzylic radical with a catalytically generated enamine. Mechanistic studies provide evidence for SCS as a key elementary step, identify the origins of competing reactions, and enable improvements in chemoselectivity by rational photocatalyst design.
Synthesis method for 4-methoxy methylpyridine
-
Paragraph 0023; 0024; 0027; 0030; 0034, (2017/11/04)
The invention belongs to the field of organic chemistry and particularly relates to a synthesis method for 4-methoxy methylpyridine. The method comprises the following steps of adopting 4-methylpyridine as a raw material and obtaining 4-bromo-methylpyridine through bromination reaction; reacting the 4-bromo-methylpyridine with trimethylamine to obtain (4-pyridylmethyl) trimethyl ammonium bromide; and dissolving the (4-pyridylmethyl) trimethyl ammonium bromide into methanol, adding sodium methylate, carrying out heating reflux under nitrogen for an hour to obtain the 4-methoxy-methyl pyridine. After the synthesis method is adopted, the 4-methylpyridine is adopted as the raw material to obtain the 4-bromo-methylpyridine through the bromination reaction, and the 4-bromo-methylpyridine reacts with the trimethylamine to obtain (4-pyridylmethyl) trimethyl ammonium bromide, and the (4-pyridylmethyl) trimethyl ammonium bromide finally reacts with the sodium methylate to obtain the 4-methoxy methylpyridine. The synthesis method is high in total yield, low in raw material price, short in reaction time, mild in condition and simple in technological operation.
2-Aminopyridine-based Selective Neuronal Nitric Oxide Synthase Inhibitors
-
Paragraph 0020; 0021, (2014/09/29)
Aminopyridine compounds, as can be used in conjunction with methods for modulation of nitric oxide synthase activity.
Regioselectivity in free radical bromination of unsymmetrical dimethylated pyridines
Thapa, Rajesh,Brown, Jordan,Balestri, Thomas,Taylor, Richard T.
supporting information, p. 6743 - 6746 (2015/01/09)
During a literature review some curious inconsistencies in the free radical bromination of picolines were noted. To achieve a better understanding of the mechanisms and regioselectivity we reran these reactions, extending our work to unsymmetrical lutidin
Substituted cycloalkyl P1' hepatitis C virus inhibitors
-
Page/Page column 64, (2010/02/06)
The present invention relates to tripeptide compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. In particular, the present invention provides novel tripeptide analogs, pharmaceutical compositions containing such analogs and methods for using these analogs in the treatment of HCV infection.
Mass spectrometric investigation of tautomers of N-substituted 4-iminopentan-2-ones in the gas phase
Urbaniak,Franski,Gierczyk
, p. 429 - 441 (2007/10/03)
Mass fragmentation of 4-iminopentan-2-one N-substituted with organosilicon group suggests that in the gas phase upon electron ionization (EI) conditions only 4-imino-2-keto tautomer occurs. The simultaneous occurrence of 4-aminopent-3-en-2-keto tautomeric form was ruled out on the basis of mass fragmentation of some alkylaromatic derivatives of 4-aminopent-3-en-2-one.
Synthesis and Pharmacology of a Series of 3- and 4-(Phosphonoalkyl)pyridine- and piperidine-2-carboxylic Acids. Potent N-Methyl-D-aspartate Receptor Antagonists
Ornstein, Paul L.,Schaus, John M.,Chambers, John W.,Huser, Diane L.,Leander, J. David,et al.
, p. 827 - 833 (2007/10/02)
We recently prepred a series of 3- and 4-(phosphonoalkyl)pyridine- and piperidine-2-carboxylic acids as antagonists of neurotransmission at N-methyl-D-aspartate (NMDA) preferring receptors.NMDA antagonists may prove to be useful therapeutic agents, for instance, as anticonvulsants, in the treatment of neurodegenerative disorders such as Alzheimer's disease and in the prevention of neuronal damage that occurs during cerebral ischemia.The compounds prepared were evaluated for their ability to displace CPP binding (an assay shown to be selective for compounds that bind at the NMDA receptor) and for their ability to block NMDA-induced lethality in mice (an assay that is also specific for competitive and noncompetitive NMDA antagonists).Two of the compounds, cis-4-(phosphonomethyl)piperidine-2-carboxylic acid (11a) and cis-4-(3-phosphonoprop-1-yl)piperidine-2-carboxylic acid (11c) proved to be potent NMDA antagonists. 11a and 11c displaced CPP binding with IC 50's of 95 and 120 nM, respectively, and both protected mice from NMDA-induced lethality, with MEDs (minimum effective dose, the dose at which three of the five animals tested survived) of 10 and 40 mg/kg ip, respectively.The rest of the compounds prepared were weakly active or inactive in these assays.The pattern of activity observed for this series parallels that observed for the acyclic series of ω-phosphono-α-amino acids, where AP5 and AP7 possessed NMDA antagonist activity while AP6 and AP8 were inactive.Reduction of conformational mobility by incorporation of the piperidine ring led to enhanced potency relative to the acyclic analogues.
