- Adamantyl aziridines via aza-Michael initiated ring closure (aza-MIRC) reaction
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An efficient one-pot synthesis of functionalized adamantylaziridines by aza-Michael initiated ring closure (aza-MIRC) reaction of 1-aminoadamantane with α-halogenated Michael acceptors is described. The reaction goes through an aza-Michael intermediate th
- Fedotova, Alena I.,Komarova, Tatiana A.,Romanov, Alexey R.,Ushakov, Igor A.,Legros, Julien,Maddaluno, Jacques,Rulev, Alexander Yu.
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- Synthesis, evaluation and application of polycyclic fluorescent analogues as N-methyl-d-aspartate receptor and voltage gated calcium channel ligands
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A series of polycyclic fluorescent ligands were synthesised and evaluated in murine striatal synaptoneurosomes for N-methyl-d-aspartate receptor (NMDAR) mediated calcium flux inhibition and inhibition of calcium influx through voltage gated calcium channe
- Joubert, Jacques,Dyk, Sandra Van,Green, Ivan R.,Malan, Sarel F.
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experimental part
p. 5010 - 5020
(2011/11/29)
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- Synthesis and antiplatelet activity of new imidazole-4-carboxylic acid derivatives
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1-Arylalkyl-5-phenylsulfonamino-imidazole-4-carboxylic acid esters and their carboxamides with an additional secondary amino group were synthesized and identified as antiplatelet agents in a low micromolar range (Born-test, inducer collagen). To describe the mechanism of action more precisely the Born-test was carried out as well with ADP, adrenaline or PAF, respectively. In addition, two compounds were investigated for their COX-1 inhibitory activities. Provided the essential structural criteria are met i.e. amide group or ester, sulfonylamino rest, hydrophobic moieties, and a secondary amino function, slight structural modifications are able to shift the pattern of activity among the above platelet receptors. So, the ester 5c exhibits PAF antagonistic activity at IC 50 = 1 μM and COX-1 inhibition (IC50 = 0.4 μM). The carboxamide 6c shows ADP antagonistic properties (IC50 = 2 μM). Compound 6g is as well PAF antagonistic (IC50 = 4 μM) and a COX-1 inhibitor (IC50 = 1 μM). The derivative 6i shows a strong antiadrenergic (IC50 = 0.15 μM) and PAF antagonistic (IC 50 = 0.66 μM) effect.
- Rehse, Klaus,Steege, Jens
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p. 539 - 547
(2007/10/03)
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- Generation and in situ evaluation of libraries of poly(acrylic acid) presenting sialosides as side chains as polyvalent inhibitors of influenza- mediated hemagglutination
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This paper describes a simple, microscale method for generating and evaluating libraries of derivatives of poly(acrylic acid) (pAA) that present mixtures of side chains that influence their biological activity. The method is based on the one-step conversion of poly(acrylic anhydride) (pAAn) to linear polymers presenting multiple units of R on side chains, pAA(R): the polymers are obtained by ultrasonication of a suspension of pAAn and aqueous RNH2 contained in a 250-μL well of a microtiter plate. Using this method, derivatives of pAA having N-acetylneuraminic acid (NeuAc-L-NH2) as a side chain, pAA(NeuAc-L), were generated and assayed for ability to inhibit hemagglutination (HAI) of chicken erythrocytes by influenza virus A (X-31); the constant (K(i)/(HAI)) describing this inhibition is calculated on the basis of the concentration of NeuAc groups in solution, rather than the concentration of polymer molecules. Co-polymeric pAA(NeuAc-L(n);L(n) = different linking groups) with a range of mole fractions of NeuAc-L-NH2 (χ(NeuAc-L) = 0.02-0.11) exhibited HAI activities with K(i)/(HAI) values between 27 and 0.30μM. Using combinations of NeuAc-L-NH2 and one of 26 different primary amines RNH2, a variety of ter-polymeric pAA(NeuAc-L; R) (χ(NeuAc-L) ~ 0.05; χ(R) ~ 0.06) were also generated and assayed. Certain terpolymers yielded values of K(i)/(HAI) that were lower by a factor of ~104 than that of the parent co-polymeric pAA(NeuAc-L): the most active inhibitor was pAA(NeuAc-L; L-3-(2'-naphthyl)alanine)) (K(i)/(HAI) ? 0.5 nM). Typically, the incorporation of hydrophobic-especially aromatic-side chains enhanced activities. These polymers (pAA(NeuAc-L; R)) belong to a new class of polymeric, polyvalent sialosides that are potent inhibitors of the adsorption of influenza virus to erythrocytes. They were active with only low to moderate levels of incorporation of functional groups into the side chains: χ(NeuAc)-L ~ 0.05; χ(R) ~ 0.06.
- Choi, Seok-Ki,Mammen, Mathai,Whitesides, George M.
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p. 4103 - 4111
(2007/10/03)
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