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Ruthenium (II)–arene complexes with chelating quinoline ligands as anti-amyloid agents
Meiss, Cade J ; Bothwell, Paige J ; Webb, Michael I Can. J. Chem.,2022,100(1):18-24. DOI: 10.1139/cjc-2021-0180
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Abstract: Recent recognition of the soluble form of the amyloid-beta (Ab) peptide as a neurotoxic agent in Alzheimer’sdis ease (AD) has spurred the development of agents to target this species. Because Ab is known to chelate metal ions in solu tion, metal-based therapeutics are uniquely suited to exploit this affinity, where coordination to Ab has been shown to impact the neurotoxicity of the peptide. Ruthenium(II)–arene complexes are unique candidates for evaluation, as one face ofthemoleculeisblockedbythehydrophobicarenering,whilecoordinationtotheAb peptide can occur on the other side of the molecule. We have prepared and evaluated two Ru(II)–arene complexes with chelating quinoline-based ligands, Ru1 and Ru2, for their respective anti-amyloid abilities. Although both complexes decreased the aggregation of soluble Ab, Ru1 displayed promise in disrupting formed aggregates of the peptide. These findings represent an exciting new avenue for therapeutic development in AD, where both sides of the aggregation equilibrium are affected.
Keywords: Alzheimer’s disease ; amyloid-beta ; ruthenium(II) therapeutics ; peptide aggregation
Purchased from AmBeed: 578-66-5
CAS No. : | 578-66-5 | MDL No. : | MFCD00006809 |
Formula : | C9H8N2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | WREVVZMUNPAPOV-UHFFFAOYSA-N |
M.W : | 144.17 | Pubchem ID : | 11359 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In methanol; for 2.5h;Reflux; | 6-Methoxy-2-pyridinecarboxaldehyde (0.65 mL, 5.40 mmol) and 8-aminoquinoline (0.77 g,5.37 mmol) were dissolved in 25 mL of anhydrous methanol and the resulting mixture was heated at reflux temperature for 2.5 h. The solvent was removed under reduced pressure togive brown solids. Yield: 1.20 g (85percent). Anal. Calcd (percent) for C16H13N3O (M = 263.30 g mol?1): C,72.99; H, 4.98; N, 15.96. Found: C, 72.85; H, 4.90; N, 15.97. FT-IR (KBr, cm?1): 3444(w), 3040(w),2948(w), 2822(w), 1651(m), 1599(s), 1576(s), 1517(s), 1470(s), 1440(m), 1415(m), 1379(m),1335(m), 1291(m), 1264(m), 1234(w), 1215(w), 1189(w), 1148(m), 1058(m), 1033(s), 990(m),894(w), 820(s), 791(s), 746(m), 643(w), 578(w), 524(w), 513(w), 747(w), 455(w). 1H NMR(400 MHz, CDCl3): delta 9.00 (s, 1H, Quinolone-H2), 8.79 (s, 1H, CH = N), 7.38?8.08 (m, 5H,Quinolone-H3,4,5,6,7), 6.95?7.19 (m, 3H, Py-H3,4,5), 4.05 (s, 3H, -OCH3) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With pyridine; triphenyl phosphite; at 110℃; for 4h;Inert atmosphere; Schlenk technique; | General procedure: The ligands were synthesized according to published methods withminor modifications [26-28]. To a solution of either 8-aminoquinolineor picolinamide (5.00×10-3 mol) in 10 mL dry pyridine was added asolution of the corresponding picolinic acid or 1-isoquinolinecarboxylicacid or <strong>[6624-49-3]3-isoquinolinecarboxylic acid</strong> (5.00×10-3 mol) in 10 mL. Themixture was stirred, heated to 110 C and triphenylphosphite(5.00×10-3 mol) was added drop-wise. The resulting brown solutionwas refluxed for 4 h. |
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