6560-65-2Relevant academic research and scientific papers
Synthesis, antibacterial and antitumor activity of methylpyridinium salts of pyridoxine functionalized 2-amino-6-sulfanylpyridine-3,5-dicarbonitriles
Grigor’ev, Arthur A.,Shtyrlin, Nikita V.,Gabbasova, Raylya R.,Zeldi, Marina I.,Yu. Grishaev, Denis,Gnezdilov, Oleg I.,Balakin, Konstantin V.,Nasakin, Oleg E.,Shtyrlin, Yurii G.
, p. 2288 - 2304 (2018)
A library of 29 2-amino-6-sulfanylpyridine-3,5-dicarbonitriles functionalized with a pyridoxine moiety was synthesized using a three-component one-pot reaction of aldehyde derivative of pyridoxine, malononitrile, and thiophenol. The obtained bipyridine structures were converted into methylpyridinium salts. Several compounds demonstrated expressed antibacterial activity with MICs (minimum inhibitory concentrations) in the range of 0.5–4 μg/mL against the three studied Gram-positive strains and 8–64 μg/mL against the Gram-negative E. coli strain, which was comparable or better than the activity of the reference antimicrobial agents. At the same time, all the synthesized compounds were inactive against the Gram-negative P. aeruginosa. Several compounds also demonstrated high cytotoxic activity against the studied tumor cells, but without selectivity for the normal HSF (human foreskin fibroblast) cells. Despite the preliminary character of the performed biological studies, the obtained results make the obtained structural chemotype a promising starting point for the design of physiologically active compounds.
Design and synthesis of novel pyridoxine 5′-phosphonates as potential antiischemic agents
Pham, Vinh,Zhang, Wenlian,Chen, Vince,Whitney, Tara,Yao, John,Froese, Doug,Friesen, Albert D.,Diakur, James M.,Haque, Wasim
, p. 3680 - 3687 (2003)
On the basis of previous reports that the natural cofactor pyridoxal 5′-phosphate 1 appears to display cardioprotective properties, a series of novel mimetics of this cofactor were envisioned. As pyridoxal 5′-phosphate is a natural compound and is subject to biological degradation and elimination pathways, the objective was to generate active phosphonates that are potentially less light sensitive and more stable in vivo than the parent vitamer. Several phosphonates were designed and synthesized, and in particular, compounds 10 and 14 displayed similar biological traits to natural phosphate 1 in the rat model of regional myocardial ischemia and reperfusion. A reduction in infarct size was observed in animals treated with these compounds. In an effort to identify other relevant cardioprotective models in order to potentially define structure - activity relationships, these three compounds were tested in the rat working heart model. Compounds 1, 10, and 14 were compared to dichloroacetic acid (DCA) as positive control in this model. As with DCA, compounds 1, 10, and 14 were found to induce a shift from fatty acid oxidation toward glucose oxidation.
SAR of non-hydrolysable analogs of pyridoxal 5′-phosphate against low molecular weight protein tyrosine phosphatase isoforms
DeSouza, Shirin R.,Flynn, Rebecca S.,Jakubowski, Henry V.,Marshall, Quinlen F.,McIntee, Edward J.,Olson, Maxwell C.,Sinner, Erica K.,Tinucci, Samantha L.
supporting information, (2020/07/21)
Kinases and phosphatases are key enzymes in cell signal transduction pathways. Imbalances in these enzymes have been linked to numerous disease states ranging from cancer to diabetes to autoimmune disorders. The two isoforms (IFA and IFB) of Low Molecular Weight Protein Tyrosine Phosphatase (LMW-PTP) appear to play a role in these diseases. Pyridoxal 5′-phosphate (PLP) has been shown to act as a potent but, impractical micromolar inhibitor for both isoforms. In this study, a series of non-hydrolysable phosphonate analogs of PLP were designed, synthesized and tested against the two isoforms of LMW-PTP. Assay results demonstrated that the best inhibitor for both isoforms was compound 5 with a Kis of 1.84 μM (IFA) and 15.6 μM (IFB). The most selective inhibitor was compound 16, with a selectivity of roughly 370-fold for IFA over IFB.
Rapid Entry into Biologically Relevant α,α-Difluoroalkylphosphonates Bearing Allyl Protection-Deblocking under Ru(II)/(IV)-Catalysis
Panigrahi, Kaushik,Fei, Xiang,Kitamura, Masato,Berkowitz, David B.
supporting information, p. 9846 - 9851 (2019/12/24)
A convenient synthetic route to α,α-difluoroalkylphosphonates is described. Structurally diverse aldehydes are condensed with LiF2CP(O)(OCH2CH-CH2)2. The resultant alcohols are captured as the pentafluorophenyl thionocarbonates and efficiently deoxygenated with HSnBu3, BEt3, and O2, and then smoothly deblocked with CpRu(IV)(π-allyl)quinoline-2-carboxylate (1-2 mol %) in methanol as an allyl cation scavenger. These mild deprotection conditions provide access to free α,α-difluoroalkylphosphonates in nearly quantitative yield. This methodology is used to rapidly construct new bis-α,α-difluoroalkyl phosphonate inhibitors of PTPIB (protein phosphotyrosine phosphatase-1B).
Synthesis of hydrolysis-resistant pyridoxal 5′-phosphate analogs and their biochemical and X-ray crystallographic characterization with the pyridoxal phosphatase chronophin
Knobloch, Gunnar,Jabari, Nauras,Stadlbauer, Sven,Schindelin, Hermann,K?hn, Maja,Gohla, Antje
, p. 2819 - 2827 (2015/03/30)
A set of phosphonic acid derivatives (1-4) of pyridoxal 5′-phosphate (PLP) was synthesized and characterized biochemically using purified murine pyridoxal phosphatase (PDXP), also known as chronophin. The most promising compound 1 displayed primarily competitive PDXP inhibitory activity with an IC50 value of 79 μM, which was in the range of the Km of the physiological substrate PLP. We also report the X-ray crystal structure of PDXP bound to compound 3, which we solved to 2.75 ? resolution (PDB code 5AES). The co-crystal structure proves that compound 3 binds in the same orientation as PLP, and confirms the mode of inhibition to be competitive. Thus, we identify compound 1 as a PDXP phosphatase inhibitor. Our results suggest a strategy to design new, potent and selective PDXP inhibitors, which may be useful to increase the sensitivity of tumor cells to treatment with cytotoxic agents.
NOVEL PYRIDINE CARBOXYLIC ACID BASED COMPOUND USED AS A P2X1 AND P2X3 RECEPTOR ANTAGONIST, A PRODUCTION METHOD FOR THE SAME AND A COMPOSITION COMPRISING THE SAME
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Paragraph 0119; 0120; 0121, (2013/03/26)
Provided are a novel pyridine carboxylic acid based compound used as a P2X1 and P2X3 receptor antagonist, a production method for the same and a composition comprising the same. The compound according to the present invention is a powerful antagonist of P2X1 and P2X3 receptors, and hence can be used as a drug for treating or preventing diseases involving neurological pain or chronic inflammatory diseases which are diseases caused by P2X1 and P2X3 receptor activity.
Synthesis and structure-activity relationships of carboxylic acid derivatives of pyridoxal as P2X receptor antagonists
Jung, Kwan-Young,Cho, Joong-Heui,Lee, Jung Sun,Kim, Hyo Jun,Kim, Yong-Chul
, p. 2643 - 2650 (2013/06/27)
Carboxylic acid derivatives of pyridoxal were developed as potent P2X 1 and P2X3 receptor antagonists with modifications of a lead compound, pyridoxal-5′-phosphate-6-azophenyl-2′,5′- disulfonate (5b, iso-PPADS). The designing strategies included the modifications of aldehyde, phosphate or sulfonate groups of 5b, which may be interacted with lysine residues of the receptor binding pocket, to weak anionic carboxylic acid groups. The corresponding carboxylic acid analogs of pyridoxal-5′- phosphate (1), 13 and 14, showed parallel antagonistic potencies. Also, most of 6-azophenyl derivatives (24-28) of compound 13 or 14 showed potent antagonistic activities similar to that of 5b at human P2X3 receptors with 100 nM range of IC50 values in two-electrode voltage clamp (TEVC) assay system on the Xenopus oocyte. The results indicated that aldehyde and phosphoric or sulfonic acids in 5b could be changed to a carboxylic acid without affecting antagonistic potency at mouse P2X1 and human P2X3 receptors.
PYRIDOXAL-5′-PHOSPHATE AND RELATED COMPOUNDS IN COMBINATION WITH THERAPEUTIC CADIOVASCULAR COMPOUNDS FOR TREATING ANGINA.
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Page/Page column 24-25; 33; 37; 34, (2008/06/13)
Methods for treating angina are described. A method. for treating angina is directed to concurrently administering a compound with a therapeutic cardiovascular compound. The combination therapy described employs suitable therapeutic cardiovascular compounds, such as an a calcium channel blocker, a β-adrenergic blocker, nitrates, partial fatty acid oxidation inhibitors, potassium channel activators, or a mixture thereof, in combination with a compound such as pyridoxal-5'-phosphate, pyridoxic acid, pyridoxal, pyridoxine, pyridoxamine, 3-acylated analogues of pyridoxal, 3-acylated analogues of pyridoxal-4,5-aminal, pyridoxine phosphonate analogues, a pharmaceutically acceptable acid addition salt thereof, or a mixture thereof. The invention also includes a novel composition comprising at least one compound and nitrates, partial fatty acid oxidation inhibitors, potassium channel activators, calcium channel blockers, β-adrenergic blockers, or a mixture thereof.
Process for the preparation of 1,3-Dihydro-6-methylfuro(3,4-c)pyridin-7-ol Derivatives
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Page 9, (2008/06/13)
The present invention relates to a process for the preparation of 1,3-dihydro-6-methylfuro[3,4-c]pyridin-7-ol derivatives and salts thereof.
Artificial transaminases linking pyridoxamine to binding cavities: Controlling the geometry
Breslow, Ronald,Canary, James W.,Varney, Michael,Waddell, Sherman T.,Yang, Dan
, p. 5212 - 5219 (2007/10/02)
A transaminase mimic joining a pyridoxamine unit to a cyclodextrin by a single linkage is quite selective for the conversion of phenylpyruvic acid to phenylalanine, compared with its reactivity toward nonbinding ketoacids. The selectivity is even greater
