57148-27-3Relevant academic research and scientific papers
Discovery and Mechanism of Action of Small Molecule Inhibitors of Ceramidases**
Arenz, Christoph,Basu, Shibom,Bechara, Cherine,Bossis, Guillaume,Cong, Xiaojing,Del Nero, Elise,Drapeau, Marion,Fontanel, Simon,Gabellier, Ludovic,Golebiowski, Jér?me,Granier, Sebastien,Healey, Robert D.,Hornemann, Thorsten,Jeannot, Sylvain,Karsai, Gergely,Leyrat, Cedric,Maurel, Damien,Saied, Essa M.,Saint-Paul, Julie
supporting information, (2021/12/09)
Sphingolipid metabolism is tightly controlled by enzymes to regulate essential processes in human physiology. The central metabolite is ceramide, a pro-apoptotic lipid catabolized by ceramidase enzymes to produce pro-proliferative sphingosine-1-phosphate. Alkaline ceramidases are transmembrane enzymes that recently attracted attention for drug development in fatty liver diseases. However, due to their hydrophobic nature, no specific small molecule inhibitors have been reported. We present the discovery and mechanism of action of the first drug-like inhibitors of alkaline ceramidase 3 (ACER3). In particular, we chemically engineered novel fluorescent ceramide substrates enabling screening of large compound libraries and characterized enzyme:inhibitor interactions using mass spectrometry and MD simulations. In addition to revealing a new paradigm for inhibition of lipid metabolising enzymes with non-lipidic small molecules, our data lay the ground for targeting ACER3 in drug discovery efforts.
3-(dimethylaminomethyl) piperidine-4-alcohol derivative as well as preparation method and pharmaceutical application thereof
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Paragraph 0111-0115, (2021/05/08)
The present invention provides compounds of formula (FWBF) or pharmaceutically acceptable salts thereof, in which the substituents are as defined in the specification, as well as a preparation method and pharmaceutical use thereof.
Discovery of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)-N-phenylpiperidine-1-carboxamide as novel potent analgesic
Fu, Wei,Huang, Huoming,Li, Wei,Liu, Jinggen,Wang, Wenli,Wang, Yujun,Xu, Xuejun,Zhu, Chen
, (2020/01/28)
Management of moderate to severe pain by clinically used opioid analgesics is associated with a plethora of side effects. Despite many efforts have been dedicated to reduce undesirable side effects, moderate progress has been made. In this work, starting from Tramadol, a series of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)piperidine-1-carboxamide derivatives were designed and synthesized, and their in vitro and in vivo activities were evaluated. Our campaign afforded selective μ opioid receptor (MOR) ligand 2a (KiMOR: 7.3 ± 0.5 nM; KiDOR: 849.4 ± 96.6 nM; KiKOR: 49.1 ± 6.9 nM) as potent analgesic with ED50 of 3.1 mg/kg in 55 °C hot plate model. Its antinociception effect was blocked by opioid antagonist naloxone. High binding affinity toward MOR of compound 2a was associated with water bridge, salt bridge, hydrogen bond and hydrophobic interaction with MOR. The high selectivity of compound 2a for MOR over δ opioid receptor (DOR) and κ opioid receptor (KOR) was due to steric hindrance of compound 2a with DOR and KOR. 2a, a compound with novel scaffold, could serve as a lead for the development of novel opioid ligands.
Synthesis and antimicrobial activity of novel 1-[3-(1,8-naphthyridin-2-yl)phenyl]-3-arylurea derivatives
Bhasker, G Vijaya,Satyanarayana,Latha,Laxminarayana,Chary, M Thirumala
, p. 771 - 774 (2018/03/13)
2-Aminonicotinaldehyde (1) and 1-(3-nitrophenyl)ethanone (2) react each other in presence of piperidine to form 2-(3-nitrophenyl)-1,8-naphthyridine (3). Compound 3 on reduction with hydrazine hydrate offered 3-(1,8-naphthyridin-2-yl)aniline (4), which on
N-(3,5-dimethyladamantane-1-yl)-N'-substituted phenylurea compound as well as preparation method and application thereof
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Paragraph 0072; 0073; 0156; 0157, (2017/12/28)
The invention belongs to the technical field of medicinal chemistry, in particular to N-(3,5-dimethyladamantane-1-yl)-N'-substituted phenylurea compounds as well as preparation methods and application thereof. The compounds have the structure shown in the formula I. The compounds are proved that the compounds can improve the image recognition memory, the working and learning memory, the spatial learning and memory ability of model rats and has good anti-alzheimer effects by the new object discrimination experiments, Y-maze experiments, positioning navigation and space exploration experiments in mats. The formula I is shown in the description.
Design and synthesis of novel triazole antifungal derivatives by structure-based bioisosterism
Sheng, Chunquan,Che, Xiaoying,Wang, Wenya,Wang, Shengzheng,Cao, Yongbing,Miao, Zhenyuan,Yao, Jianzhong,Zhang, Wannian
experimental part, p. 5276 - 5282 (2011/12/03)
The incidence of life-threatening fungal infections is increasing dramatically. In an attempt to develop novel antifungal agents, our previously synthesized phenoxyalkylpiperazine triazole derivatives were used as lead structures for further optimization. By means of structure-based bioisosterism, triazolone was used as a new bioisostere of oxygen atom. This type of bioisosteric replacement can improve the water solubility without loss of hydrogen-bonding interaction with the target enzyme. A series of triazolone-containing triazoles were rationally designed and synthesized. As compared with fluconazole, several compounds showed higher antifungal activity with broader spectrum, suggesting their potential for further evaluations.
