20329-98-0Relevant articles and documents
Iron-catalyzed domino decarboxylation-oxidation of α,β-unsaturated carboxylic acids enabled aldehyde C-H methylation
Gong, Pei-Xue,Xu, Fangning,Cheng, Lu,Gong, Xu,Zhang, Jie,Gu, Wei-Jin,Han, Wei
supporting information, p. 5905 - 5908 (2021/06/18)
A practical and general iron-catalyzed domino decarboxylation-oxidation of α,β-unsaturated carboxylic acids enabling aldehyde C-H methylation for the synthesis of methyl ketones has been developed. This mild, operationally simple method uses ambient air as the sole oxidant and tolerates sensitive functional groups for the late-stage functionalization of complex natural-product-derived and polyfunctionalized molecules.
Amino Group Functionalized Hf-Based Metal-Organic Framework for Knoevenagel-Doebner Condensation
Das, Aniruddha,Anbu, Nagaraj,Gogoi, Chiranjib,Dhakshinamoorthy, Amarajothi,Biswas, Shyam
, p. 3396 - 3403 (2021/08/20)
A Hf(IV) metal-organic framework (MOF) with di-amino functionalized linker was obtained as a crystalline solid with UiO-67 topology under solvothermal reaction conditions. The guest free form of Hf(IV) MOF (1′) was efficiently employed as a heterogeneous catalyst to synthesize cinnamic acid derivatives via Knoevenagel-Doebner reaction for the first time. The catalyst (1′) was efficiently active to directly achieve cinnamic acid from benzaldehyde and malonic acid. The solid retained its activity up to 6th cycle with no decay in its activity. The noticeable advantages of the catalyst are its milder reaction conditions, high yield, high stability, recyclable nature towards catalysis and wide substrate scope as well as shape-selective behaviour. The possible mechanism of the reaction was also studied thoroughly with suitable control experiments.
First synthesis of tabamides A–C and their derivatives: In vitro nitric oxide inhibitory activity
Damodar, Kongara,Jeon, Sung Ho,Lee, Jeong Tae,Shin, Sooyong
supporting information, (2021/11/10)
The first synthesis of natural phenolic amides, tabamides A–C (1–3), and their derivatives (4–12) was accomplished using Stobbe condensation and amide coupling reactions as key steps. The in vitro nitric oxide (NO) inhibitory effects of these compounds in LPS-induced RAW-264.7 macrophages were evaluated as an indicator of anti-inflammatory activity. All compounds tested had a concentration-dependent inhibitory effect on NO production by RAW-264.7 macrophages without significant cytotoxicity. Compound 6, a tabamide A derivative (IC50 = 82.6 μM), followed by tabamide A (1, IC50 = 100.7 μM), was the most potent from the series. The present study revealed that tabamide A (1) could be considered as a lead structure to develop NO production-targeted anti-inflammatory agents.
Identification of novel functionalized carbohydrazonamides designed as chagas disease drug candidates
Do Nascimento, Mayara S. S.,Camara, Vitória R. F.,da Costa, Juliana S.,Barbosa, Juliana M. C.,Lins, Alessandra S. M.,Salom?o, Kelly,de Castro, Solange L.,Carvalho, Samir A.,da Silva, Edson F.,Fraga, Carlos A. M.
, p. 774 - 783 (2020/08/19)
Background: Although several research efforts have been made worldwide to discover novel drug candidates for the treatment of Chagas disease, the nitroimidazole drug benznidazol remains the only therapeutic alternative in the control of this disease. However, this drug presents reduced efficacy in the chronic form of the disease and limited safety after long periods of admini-stration, making it necessary to search for new, more potent and safe prototypes. Objective: We described herein the synthesis and the trypanocidalaction of new functionalized carbohydrazonamides (2-10) against trypomastigote forms of Trypanosoma cruzi. Methods: These compounds were designed through the application of molecular hybridization concept between two potent anti-T. cruzi prototypes, the nitroimidazole derivative megazol (1) and the cinnamyl N-acylhydrazone derivative (14) which have been shown to be twice as potent in vitro as benznidazole. Results: The most active compounds were the (Z)-N'-((E)-3-(4-nitrophenyl)-acryloyl)-1-methyl-5-nitro-1H-imidazol-2-carbohydrazonamide (6) (IC50 =9.50 μM) and the (Z)-N'-((E)-3-(4-hydroxyphe-nyl)-acryloyl)-1-methyl-5-nitro-1H-imidazol-2-carbohydrazonamide (8) (IC50 =12.85 μM), which were almost equipotent to benznidazole (IC50 =10.26 μM) used as standard drug. The removal of the amine group attached to the imine subunit in the corresponding N-acylhydrazone derivatives (11-13) resulted in less potent or inactive compounds. The para-hydroxyphenyl derivative (8) presented also a good selectivity index (SI = 32.94) when tested against mammalian cells from Swiss mice. Conclusion: The promising trypanocidal profile of new carbohydrazonamide derivatives (6) and (8) was characterized. These compounds have proved to be a good starting point for the design of more effective trypanocidal drug candidates.
Synthesis and Spectroscopic Analysis of Piperine- And Piperlongumine-Inspired Natural Product Scaffolds and Their Molecular Docking with IL-1β and NF-κB Proteins
Cornelio, Marinonio L.,Jones, Alan M.,Le Duff, Cécile S.,Povinelli, Ana Paula R.,Tang, Bridget,Zazeri, Gabriel
, (2020/07/02)
Inspired by the remarkable bioactivities exhibited by the natural products, piperine and piperlongumine, we synthesised eight natural product-inspired analogues to further investigate their structures. For the first time, we confirmed the structure of the key cyclised dihydropyrazolecarbothioamide piperine analogues including the use of two-dimensional (2D) 15N-based spectroscopy nuclear magnetic resonance (NMR) spectroscopy. Prior investigations demonstrated promising results from these scaffolds for the inhibition of inflammatory response via downregulation of the IL-1β and NF-κB pathway. However, the molecular interaction of these molecules with their protein targets remains unknown. Ab initio calculations revealed the electronic density function map of the molecules, showing the effects of structural modification in the electronic structure. Finally, molecular interactions between the synthesized molecules and the proteins IL-1β and NF-κB were achieved. Docking results showed that all the analogues interact in the DNA binding site of NF-κB with higher affinity compared to the natural products and, with the exception of 9a and 9b, have higher affinity than the natural products for the binding site of IL-1β. Specificity for the molecular recognition of 3a, 3c and 9b with IL-1β through cation–π interactions was determined. These results revealed 3a, 3c, 4a, 4c and 10 as the most promising molecules to be evaluated as IL-1β and NF-κB inhibitors.
Synthesis, biological evaluation and computational studies of acrylohydrazide derivatives as potential Staphylococcus aureus NorA efflux pump inhibitors
Kumar, Gautam,Goutami Godavari, Ambati,Tambat, Rushikesh,Kumar, Siva,Nandanwar, Hemraj,Elizabeth Sobhia,Jachak, Sanjay M.
, (2020/10/02)
The NorA efflux pump decreases the intracellular concentration of fluoroquinolones (ciprofloxacin, norfloxacin) by effluxing them from Staphylococcus aureus cells. The synthesis of novel acrylohydrazide derivatives was achieved using well-known reactions and were characterized by various spectroscopy techniques. The synthesized 50 compounds were evaluated for the NorA efflux pump inhibition activity against S. aureus SA-1199B (norA++) and K1758 (norA-) strains. The study provided two most active compounds viz. 19 and 52. Compound 19 was found to be most active in potentiating effect of norfloxacin and also it showed enhanced uptake, efflux inhibition in ethidium bromide assay. Further compound 19 also enhanced post antibiotic effect and reduced mutation prevention concentration of norfloxacin. The homology modeling study was performed to elucidate three-dimensional structure of NorA. Docking studies of potent molecules were done to find the binding affinity and interaction with active site residues. Further, all the tested compounds exhibited good ADME and drug-likeness properties in- silico. Based on the in-silico studies and detailed in vitro studies, acrylohydrazides derivatives may be considered as potential NorA EPI candidates.
The potential role of the 5,6-dihydropyridin-2(1: H)-one unit of piperlongumine on the anticancer activity
Li, Peng-Xiao,Liu, Guo-Yun,Liu, Yue,Mu, Wen-Wen,Yang, Jie
, p. 42128 - 42136 (2020/12/09)
Piperlongumine (PL), a potent anticancer agent from the plant long pepper (Piper longum), contains the 5,6-dihydropyridin-2(1H)-one heterocyclic scaffold and cinnamoyl unit. In this paper, we synthesized a series of PL analogs and evaluated their cytotoxicity against cancer cells for the sake of exploring which pharmacophore plays a more potent role in enhancing the anticancer activities of PL. These results illustrated that the position effect, not the electronic effect, of substituents plays a certain role in the cytotoxicity of PL and its analogs. More important, the 5,6-dihydropyridin-2(1H)-one unit, a potent pharmacophore in enhancing the antiproliferative activities of PL, could react with cysteamine and lead to ROS generation, and then bring about the occurrence of ROS-induced downstream events, followed by cell cycle arrest and apoptosis. This work suggests that introducing a lactam unit containing Michael acceptors may be a potent strategy to enhancing the anticancer activity of drugs. This journal is
Preparation method for cinepazide maleate
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Paragraph 0033, (2020/04/17)
The invention provides a preparation method for cinepazide maleate, which comprises the following steps of: (1) carrying out Wittig reaction on 3, 4, 5-trimethoxybenzaldehyde serving as an initial rawmaterial and phosphine ylide to obtain (E)-3, 4, 5-trimethoxyethyl cinnamate (intermediate I), (2) hydrolyzing the (E)-3, 4, 5-trimethoxyethyl cinnamate to obtain a key intermediate 3, 4, 5-trimethoxy cinnamic acid (intermediate II), (3) in the presence of 1-hydroxybenzotriazole, triethylamine and carbodiimide hydrochloride, coupling the intermediate I with anhydrous piperazine to synthesize 1-(3, 4, 5-trimethoxycinnamoyl) piperazine (intermediate III), (4) reacting the 1-(3, 4, 5-trimethoxycinnamoyl) piperazine with 2-bromo-1 (pyrrolidine-1-yl) ethyl ketone to generate cinepazide (an intermediate IV), and (5) salifying the cinepazide in the step (4) and maleic acid to generate the target product cinepazide maleate. The preparation method has the advantages of cheap and easily available raw materials, simple operation, short production period, high yield, easy purification, good control of the product quality, reduction of the pollutant discharge, environmental protection, and realization of industrial production.
Preparation and anti-tumor activity of piplartine derivative
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Paragraph 0007, (2019/04/13)
The invention discloses a biological structural formula of a piplartine derivative. The compound is of a novel structure. The invention further discloses a preparation method and use of the compound.The compound has obvious inhibition effects to the tumor cells of pancreatic cancer, cervical cancer, colon cancer, malignant melanoma, lung adenocarcinoma, leukemia, ovarian cancer and the like. Thestructural formula of the compound is formula (shown in the description).
Mild, Metal-Free and Protection-Free Transamidation of N-Acyl-2-piperidones to Amino Acids, Amino Alcohols and Aliphatic Amines and Esterification of N-Acyl-2-piperidones
Subramani, Muthuraman,Rajendran, Saravana Kumar
supporting information, p. 3677 - 3686 (2019/06/08)
Amides are indispensable building blocks of biological systems, pharmaceuticals, and materials. We report a highly selective method for the synthesis of amides via transamidation process. Transamidation of N-acyl-2-piperidones with a broad range of amines is demonstrated under exceedingly mild and metal-free reaction condition that relies on the amide bond twist to weaken the amidic resonance. Transamidation proceeds under the neat condition at room temperature, in short reaction times (30–90 min) with good yields. Considerable variation is tolerated with both amine and imide substrates. Of note, amines bearing carboxylic acids (glycine and serine) and hydroxyl groups (dopamine, tyramine, etc.) are well tolerated which are otherwise problematic under the metal-catalyzed protocol. Our current method is applicable for transamidation of both alkyl and aryl-N-acyl-2-piperidones. The practical value of the method is highlighted by the synthesis of four natural product amide alkaloids in high yields under mild reaction conditions. In the absence of nucleophilic amines, N-acyl-2-piperidones undergoes esterification with EtOH at elevated temperature. Single crystal X-ray analysis of an N-acyl-2-piperidone shows amide bond twist, τ = –20.39° and pyramidalization, χN = –11.73°. This weakens the amidic conjugation and might be the factor controlling the reactivity and selectivity of these imides. We envision that the N-acyl-2-piperidone scaffold would be useful in the synthesis of pharmaceuticals and materials.
