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N-[(disubstituted amino)alkyl]-3,4 (or 4,5)-diaryl-1H-pyrazole-1-acetamides and pyrazole-1-propanamides, useful for treating cardiac arrhythmias in mammals, are prepared by reacting a lower-alkyl ester of pyrazole-1-acetic or propanoic acid with an appropriate diamine or by reacting a lower-alkyl ester of a pyrazole-1-acetic or propanoic acid with an omega-aminoalkanol, followed by activation of the alcohol and displacement by an appropriate amine.

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A series of twelve 2,5-bis(alkylamino)-1,4-benzoquinones were prepared in yields ranging from 9-58% via the reaction between p-benzoquinone and various amines. The structures of the synthesized compounds were confirmed by IR, 1H- and 13C-NMR and MS analyses. The phytotoxicity of the 2,5-bis(alkylamino)-1,4-benzoquinones was evaluated against two crop species, Cucumis sativus and Sorgum bicolor, at 1.0 × 10-3 mol/L. In general, the quinones displayed inhibitory effects on the dicotyledonous species C. sativus (7-74%). On the other hand stimulatory effects were observed on S. bicolor (monocotyledonous). Similar results were observed in the biological assays carried out with the weed species Ipomoea grandifolia (dicotyledonous) and Brachiaria decumbens (monocotyledonous). In addition, the cytotoxicity of the 2,5-bis(alkylamino)-1,4- benzoquinones was assayed against HL-60 (leukemia), MDA-MB-435 (melanoma), SF- 295 (brain) and HCT-8 (colon) human cancer cell lines and human peripheral blood mononuclear cells (PBMC), as representatives of healthy cells, using a MTT and an Alamar Blue assay. Compound 12 was the most active, displaying cytotoxicity against all cancer cell lines tested.

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The paradigm, derived from bicyclams and other cyclams, by which it is necessary to use the p-phenylene moiety as the central core in order to achieve high HIV-1 antiviral activities has been reexamined for the more flexible and less bulky structures 4, previously described by our group as potent HIV-1 inhibitors. The symmetrical compounds 7{x,x} and the non-symmetrical compounds 8{x,y} were designed, synthesized and biologically evaluated in order to explore the impact on the biological activity of the distance between the phenyl ring and the first nitrogen atom of the side chains. EC50 exactly followed the order 7{x,x} < 8{x,x} < 4{x,x} indicating that, for such flexible tetramines, the presence of two methylene units on each side of the central phenyl ring increases the biological activity contrary to AMD3100. A computational study of the interactions of 4{3,3}, 7{3,3} and 8{3,3} with CXCR4 revealed interactions in the same pocket region with similar binding modes for 4{3,3} and 7{3,3} but a different one for 8{3,3}. The proportionality constant is the rate constant for the particular unimolecular reaction. the reaction rate is directly proportional to the concentration of the reactant. I hope my blog about 27578-60-5 is helpful to your research. Application In Synthesis of N-(2-Aminoethyl)piperidine

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A series of structurally similar oxovanadium(V) complexes with analogous Schiff bases have been prepared and structurally characterized. The urease inhibitory activities of the complexes were investigated. The shorter the terminal groups of the Schiff base ligands are, the stronger the urease inhibitory activities of the oxovanadium(V) complexes.

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A series of N-<2-(dimethylamino)ethyl>-4-aryl-1-piperazinecarboxamides was synthesized and evaluated for antiallergy activity.Several derivatives had activity in the passive foot anaphylaxis (PFA) assay, an IgE-mediated model useful in the detection of compounds possessing antiallergic activity, but no derivative tested had activity at 10 mg/kg in the guinea pig anaphylaxis (GPA) assay.One analogue, N-<2-(dimethylamino)ethyl>-4-(4-fluorophenyl)-1-piperazinecarboxamide, had an IC50 = 310 nM for inhibition of tritiated mepyramine binding to H1 histaminic receptors isolated from guinea pig cerebral cortex.

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In a series of simple synthetic manipulations the active component of the aphrodisiac Spanish fly has resulted in the generation of a new family of room-temperature ionic liquids (RTILs). These RTILs are synthesized in high yield from readily attainable starting materials and can be generated in either meso or chiral forms dependant on the starting furan analogue. Substituted furans (2-methyl and 2-ethyl) afford chiral RTILs, furan affords a family of meso RTILs. In all cases the counterion was crucial, with CH3SO 3- consistently displaying the lowest melting points. Of the RTILs synthesized, TGA plots showed most to be stable up to at least 250C. We had sought to use these RTILs in a series of dynamic combinatorial chemistry (DCC) assembly reactions via solubulisation of dynamin GTPases pleckstrin homology (PH) domain, as such all analogues were screened as potential inhibitors. Screening reveals that these RTILs display varying levels of dynamin GTPase inhibition with a number amongst the most potent inhibitors of dynamin GTPase yet discovered, e.g.13 IC50 = 2.3 ± 0.3 muM (4-(N,N-dimethyl-N-octadecyl-N-ethyl)-4-aza-10-oxatricyclo[5.2.1]decane-3, 5-dione bromide. Accordingly these RTILs have limited utility for DCC assembly with dynamin GTPase, but may be of use with other proteins or in other fields of study. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.

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The preparation of 1,3,2-benzodithiazole S-oxide analogs exhibiting in vitro antifungal activity against several strains of Candida is described.For the preparation of derivatives bearing aromatic substituents, a novel electrophilic aromatic thiolation reaction was utilized which produced substituted aromatic 1,2-dithiol intermediates.The reactions of nucleophiles with the parent heterocyclic system have led to an efficient transamidation process which allows for the direct production of these analogs.The S-oxide bond exhibits poor stereochemical stability and has been found to epimerize under ambient conditions.The structure-activity data report that a side chain of greater than 10 carbons effects a loss in activity as does the placement of polar groups in this chain.

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Screening of the Roche compound library led to the identification of cis-N-(2-phenyl-cyclohexyl)-spiropiperidine 1 as structurally novel GlyT1 inhibitor. The SAR, which was developed in this series, resulted in the discovery of highly potent compounds displaying excellent selectivity against the GlyT2 isoform.

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Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) is a potent and selective allosteric inhibitor of kidney-type glutaminase (GLS) that has served as a molecular probe to determine the therapeutic potential of GLS inhibition. In an attempt to identify more potent GLS inhibitors with improved drug-like molecular properties, a series of BPTES analogs were synthesized and evaluated. Our structure-activity relationship (SAR) studies revealed that some truncated analogs retained the potency of BPTES, presenting an opportunity to improve its aqueous solubility. One of the analogs, N-(5-{2-[2-(5-amino-[1,3,4] thiadiazol-2-yl)-ethylsulfanyl]-ethyl}-[1,3,4]thiadiazol-2-yl) -2-phenyl-acetamide 6, exhibited similar potency and better solubility relative to BPTES and attenuated the growth of P493 human lymphoma B cells in vitro as well as in a mouse xenograft model.

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Structure-activity studies were carried out on a series of antihypertensive 1-(2-aminoethyl)-3-(substituted phenyl)thioureas.From this class of compounds, the 2,6-dichlorophenyl analogue 2 was found to have potent oral antihypertensive activity in two hypertensive rat models and the renal hypertensive dog.In addition to its effect on blood pressure, 2 displayed sedative effects which had a marked species specificity.

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