Evaluation of Water‐Soluble Mannich Base Prodrugs of 2,3,4,5‐Tetrahydroazepino[4,3‐ b ]indol‐1(6 H )‐one as Multitarget‐Directed Agents for Alzheimer's Disease
| العنوان: | Evaluation of Water‐Soluble Mannich Base Prodrugs of 2,3,4,5‐Tetrahydroazepino[4,3‐ b ]indol‐1(6 H )‐one as Multitarget‐Directed Agents for Alzheimer's Disease |
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| المؤلفون: | Modesto de Candia, Nunzio Denora, Leonid G. Voskressensky, Mariagrazia Rullo, Rosa Purgatorio, Marco Catto, Antonio Carrieri, Cosimo Altomare, Alisa A. Nevskaya, Leonardo Pisani |
| المصدر: | ChemMedChem. 16:589-598 |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Models, Molecular, Cell Survival, Serum albumin, Mannich base, 01 natural sciences, Biochemistry, Mannich Bases, Structure-Activity Relationship, chemistry.chemical_compound, Alzheimer Disease, Oral administration, Cell Line, Tumor, Drug Discovery, medicine, Humans, Prodrugs, General Pharmacology, Toxicology and Pharmaceutics, Solubility, Cytotoxicity, Butyrylcholinesterase, Pharmacology, Dose-Response Relationship, Drug, Molecular Structure, biology, 010405 organic chemistry, Chemistry, Organic Chemistry, Neurotoxicity, Water, Prodrug, medicine.disease, Combinatorial chemistry, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Neuroprotective Agents, Acetylcholinesterase, biology.protein, Molecular Medicine, Cholinesterase Inhibitors |
| الوصف: | Different Mannich base derivatives have been studied with the aim of addressing the poor aqueous solubility of the recently disclosed 6-phenethyl-2,3,4,5-tetrahydroazepino[4,3-b]indol-1(6H)-one (1), a human butyrylcholinesterase inhibitor (hBChE, IC50 13 nM) and protective agent in NMDA-induced neurotoxicity, in in vivo assays. The N-(4-methylpiperazin-1-yl)methyl derivative 2 c showed a 50-fold increase in solubility in pH 7.4-buffered solution, high stability in serum and (half-life >24 h) and rapid ( |
| تدمد: | 1860-7187 1860-7179 |
| DOI: | 10.1002/cmdc.202000583 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::475d80d0e8dd664905cd0919676cc366 https://doi.org/10.1002/cmdc.202000583 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....475d80d0e8dd664905cd0919676cc366 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18607187 18607179 |
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| DOI: | 10.1002/cmdc.202000583 |