89040-08-4Relevant academic research and scientific papers
IMMUNOMODULATORY COMPOUNDS
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Page/Page column 15, (2014/03/21)
This invention relates to compounds and uses thereof in the treatment or prophylaxis of diseases associated with inflammation.
Designing anti-inflammatory drugs from parasitic worms: A synthetic small molecule analogue of the acanthocheilonema viteae product ES-62 prevents development of collagen-induced arthritis
Al-Riyami, Lamyaa,Pineda, Miguel A.,Rzepecka, Justyna,Huggan, Judith K.,Khalaf, Abedawn I.,Suckling, Colin J.,Scott, Fraser J.,Rodgers, David T.,Harnett, Margaret M.,Harnett, William
, p. 9982 - 10002 (2014/01/17)
In spite of increasing evidence that parasitic worms may protect humans from developing allergic and autoimmune diseases and the continuing identification of defined helminth-derived immunomodulatory molecules, to date no new anti-inflammatory drugs have been developed from these organisms. We have approached this matter in a novel manner by synthesizing a library of drug-like small molecules based upon phosphorylcholine, the active moiety of the anti-inflammatory Acanthocheilonema viteae product, ES-62, which as an immunogenic protein is unsuitable for use as a drug. Following preliminary in vitro screening for inhibitory effects on relevant macrophage cytokine responses, a sulfone-containing phosphorylcholine analogue (11a) was selected for testing in an in vivo model of inflammation, collagen-induced arthritis (CIA). Testing revealed that 11a was as effective as ES-62 in protecting DBA/1 mice from developing CIA and mirrored its mechanism of action in downregulating the TLR/IL-1R transducer, MyD88. 11a is thus a novel prototype for anti-inflammatory drug development.
Organosulfur compounds as potential fungicides: The preparation and properties of some substituted benzyl 2-hydroxyethyl oligosulfides
Ayodele, Ezekiel T.,Hudson, Harry R.,Ojo, Isaac A. O.,Pianka, Max
, p. 123 - 142 (2007/10/03)
Compounds of the general type ArCH2SnCH2CH2OH (n = 1 - 4, Ar = Ph, 2-MeC6H4. 4-MeC6H4, 4-ClC6H4, 4-MeOC6H4; n = 1 - 3, Ar = 2-ClC6H4; n = 2, Ar = 4-FC6H4; n = 3 or 4, Ar = 2-furyl) have been prepared as analogues of the trisulfide PhCH2SSSCH2CH2OH (an antimicrobial compound which occurs in the plant Petiveria alliacea) and their potential for application as agricultural fungicides has been examined. In vitro tests against Fusarium culmorum, Fusarium oxysporum and Gauennmyceles graminis showed that all compounds gave > 80% control of these organisms at 1000 ppm. Tests at 100 and 10 ppm showed varying levels of control but the activity did not depend significantly on the number of sulfur atoms present. Selected compounds were also shown to be active in vivo against Erysiphe graminis on barley seedlings, Botrytis fabae and Uromyces viciae-fabae on bean seedlings, Podosphaera leucotricha on apple seedlings, and Phytophthora infestans on potato leaf. The compounds were phytotoxic at concentrations greater than 0.33%.
Synthesis of difficult cyclic peptides by inclusion of a novel photolabile auxiliary in a ring contraction strategy
Meutermans, Wim D. F.,Golding, Simon W.,Bourne, Greg T.,Miranda, Les P.,Dooley, Michael J.,Alewood, Paul F.,Smythe, Mark L.
, p. 9790 - 9796 (2007/10/03)
Cyclic peptides comprise a large and important class of biologically active molecules. They are generally synthesized through amide bond-forming reactions of the C- and N- termini under high dilution conditions. Yields of such processes are highly dependent on the size of the ring being formed and on the particular amino acids of the linear precursor, giving rise to the well-known sequence-dependent effect of cyclization. To overcome this problem, we have developed a peptide cyclization strategy that proceeds through a ring closure/ring contraction process. The linear peptide Ala-Phe-Leu-Pro-Ala, which does not generate monocyclic product under conventional cyclization conditions, was used as a model to probe a range of auxiliaries. This has led to the development of a new photolabile peptide cyclization auxiliary. The 6-nitro-2-hydroxybenzyl group is readily and quantitatively introduced at the W-terminus via a reductive alkylation. Cyclization of the auxiliary-peptide initially proceeds through a cyclic nitrophenyl ester that preorganizes the peptide for lactamization. As the C- and N- termini are in close proximity, lactamization is achieved via an intramolecular O-N acyl transfer step to produce the N-substituted target cycle. The auxiliary is then removed by mild photolysis to produce the target cyclic peptide, cyclo-[Ala-Phe-Leu-Pro-Ala], in good yield. This strategy should find further useful applications in the assembly of libraries of small cyclic peptides.
