- Metal-free synthesis of β-aminoketones by the reductive hydroamination of ynones
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This study describes a cascade method for the synthesis of β-aminoketones through the reductive hydroamination of alkynes under very mild metal-free conditions. It allows for the rapid conversion of ynones and amines into corresponding β-aminoketones with a broad substrate scope and diverse functionalities. This straightforward and easy-to-handle reaction process can be successfully applied for the synthesis of Proroxan and Propipocaine, offering a potential option for the synthesis of drug molecules with the β-aminoketone skeleton.
- Fu, Rui,Liu, Yu,Wu, Tao,Zhang, Xinyu,Zhu, Yang,Luo, Jiangbin,Zhang, Zhengyu,Jiang, Yaojia
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p. 3525 - 3528
(2022/03/31)
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- Mechanistic studies on counter-ionic effects of camphorsulfonate-based ionic liquids on kinetics, thermodynamics and stereoselectivity of β-amino carbonyl compounds
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Catalysis is important in various applications of organic chemistry and its output product control for stereoselective compounds is outrageous. Establishment of experimental facts of stereoselective compounds from catalysis and their validation using theoretical evidences is the key to understand various mechanisms of optically active compounds. A family of new ionic liquids (ILs) with various imidazolium cations and camphorsulfonate anion as environmentally benign liquid salts have been synthesized and deployed for catalysis of β-amino carbonyl compounds. The products were formed using ILs as a homogeneous catalyst with excellent product yield and diastereoselectivity. The effect of counter ions, Hammett acidity and viscosity of ILs along with solvent and temperature are explored in terms of reaction kinetics and product yields. Density functional theory (DFT) was used to investigate thermodynamical study of mechanistic pathway of the reaction. The DFT calculations predicted that the catalysis mechanism involved both counterions of the IL. Moreover, it is evidenced that the syn-pathway required lower activation energy while anti-pathway led to thermodynamically stable product. This study explores new avenues for using ILs as potential homogeneous catalysts for the production of stereoselective species.
- Hamzah, Ahmad Sazali,Jabeen, Erum,Leveque, Jean-Marc,Sardar, Sabahat,Wilfred, Cecilia Devi
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- Evaluation of Cytotoxic Properties of N,N'-bis[(1-aryl-3-heteroaryl)propylidene]-hydrazine dihydrochlorides
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N,N'-bis[(1-aryl-3-heteroaryl)propylidene]hydrazine dihydrochlorides, P1, P4 – P8, and R1 – R7, were assayed against human oral squamous cell carcinoma (HSC-2, HSC-3, HSC-4), human promyelocytic leukemia cell line (HL-60), and human normal oral cells (HGF
- Kucukoglu,Gul,Sakagami
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p. 784 - 787
(2020/11/23)
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- Identification of dual Sigma1 receptor modulators/acetylcholinesterase inhibitors with antioxidant and neurotrophic properties, as neuroprotective agents
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In this manuscript we report on the design, synthesis and evaluation of dual Sigma 1 Receptor (S1R) modulators/Acetylcholinesterase (AChE) inhibitors endowed with antioxidant and neurotrophic properties, potentially able to counteract neurodegeneration. The compounds based on arylalkylaminoketone scaffold integrate the pharmacophoric elements of RRC-33, a S1R modulator developed by us, donepezil, a well-known AChE inhibitor, and curcumin, a natural antioxidant compound with neuroprotective properties. A small library of compounds was synthesized and preliminary in vitro screening performed. Some compounds showed good S1R binding affinity, selectivity towards S2R and N-Methyl-D-Aspartate (NMDA) receptor, AChE relevant inhibiting activity and are potentially able to bypass the BBB, as predicted by the in silico study. For the hits 10 and 20, the antioxidant profile was assessed in SH-SY5Y human neuroblastoma cell lines by evaluating their protective effect against H2O2 cytotoxicity and reactive oxygen species (ROS) production. Tested compounds resulted effective in decreasing ROS production, thus ameliorating the cellular survival. Moreover, compounds 10 and 20 showed to be effective in promoting the neurite elongation of Dorsal Root Ganglia (DRG), thus demonstrating a promising neurotrophic activity. Of note, the tested compounds did not show any cytotoxic effect at the concentration assayed. Relying on these encouraging results, both compounds will undergo a structure optimization program for the development of therapeutic candidates for neurodegenerative diseases treatment.
- Rui, Marta,Rossino, Giacomo,Coniglio, Stefania,Monteleone, Stefania,Scuteri, Arianna,Malacrida, Alessio,Rossi, Daniela,Catenacci, Laura,Sorrenti, Milena,Paolillo, Mayra,Curti, Daniela,Venturini, Letizia,Schepmann, Dirk,Wünsch, Bernhard,Liedl, Klaus R.,Cavaletti, Guido,Pace, Vittorio,Urban, Ernst,Collina, Simona
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p. 353 - 370
(2018/09/21)
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- PEG 400/cerium ammonium nitrate combined with microwave-assisted synthesis for rapid access to beta-amino ketones. an easy-to-use protocol for discovering new hit compounds
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Compound libraries are important requirement in target-based drug discovery. In the present work, a small focused compound library based on β-aminoketone scaffold has been prepared combining microwave-assisted organic synthesis (MAOS) with polymer-assiste
- Rossino, Giacomo,Raimondi, Maria Valeria,Rui, Marta,Di Giacomo, Marcello,Rossi, Daniela,Collina, Simona
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- A novel method for biomimetic synthesis of Mannich bases
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Since the early studies of Mannich, Mannich reaction has become an important tool for the synthesis of new compounds. Mannich bases can be either directly employed or used as intermediates. In this work, the one-carbon unit transfer reaction of tetrahydrofolate coenzyme was initiated. 1,3-Dimethylimidazolidine as a new tetrahydrofolate coenzyme model at formaldehyde oxidation level was used to react with ketone having active hydrogen atoms and amine to give the corresponding Mannich base in good yield by a covert Mannich reaction. A novel method for biomimetic synthesis of various Mannich bases is provided. 1,3-Dimethylimidazolidine as a new tetrahydrofolate coenzyme model at formaldehyde oxidation level was used to react with ketone having active hydrogen atoms and amine to give the corresponding Mannich base in good yield by a covert Mannich reaction. A novel method for biomimetic synthesis of various Mannich bases is provided. Copyright
- Guo, Yuan,An, Jing,Lu, Zhenhuan,Peng, Mengjiao
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experimental part
p. 1561 - 1564
(2012/10/07)
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- Electrooxidative cyclization of hydroxyamino compounds possessing a benzyl group
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Several novel 2-aryl-1,3-oxazinane and 2-aryl-1,3-oxazolidine derivatives were synthesized from N-benzyl-2-piperidineethanols and N-benzyl-2- piperidinemethanols, respectively, by using electrooxidative methods in methanol. For these reactions, the yields of the corresponding cyclized compounds were significantly increased by using catalytic amounts of iodide ions. In contrast, 3-dialkylamino-1-phenylpropanols afforded the expected cyclic 6-phenyl-1,3-oxazinane derivatives using only a small excess of base. Georg Thieme Verlag Stuttgart · New York.
- Okimoto, Mitsuhiro,Ohashi, Kousuke,Yamamori, Haruki,Nishikawa, Shinnosuke,Hoshi, Masayuki,Yoshida, Takashi
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experimental part
p. 1315 - 1322
(2012/06/30)
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- Antimalarial versus cytotoxic properties of dual drugs derived from 4-aminoquinolines and mannich bases: Interaction with DNA
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The synthesis and biological evaluation of new organic and organometallic dual drugs designed as potential antimalarial agents are reported. A series of 4-aminoquinoline-based Mannich bases with variations in the aliphatic amino side chain were prepared via a three-steps synthesis. These compounds were also tested against chloroquine-susceptible and chloroquine-resistant strains of Plasmodium falciparum and assayed for their ability to inhibit the formation of β-hematin in vitro using a colorimetric β-hematin inhibition assay. Several compounds showed a marked antimalarial activity, with IC50 and IC90 values in the low nM range but also a high cytotoxicity against mammalian cells, in particular a highly drug-resistant glioblastoma cell line. The newly designed compounds revealed high DNA binding properties, especially for the GC-rich domains. Altogether, these dual drugs seem to be more appropriate to be developed as antiproliferative agents against mammalian cancer cells than Plasmodium parasites.
- Tóth, Katalin,Wenzel, Nicole I.,Chavain, Natascha,Wang, Yulin,Friebolin, Wolfgang,Maes, Louis,Pradines, Bruno,Lanzer, Michael,Yardley, Vanessa,Brun, Reto,Herold-Mende, Christel,Biot, Christophe,Davioud-Charvet, Elisabeth
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body text
p. 3214 - 3226
(2010/10/19)
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- Synthesis of pharmacologically relevant indoles with amine side chains via tandem hydroformylation/fischer indole synthesis
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The sequence of hydroformylation and Fischer indole synthesis starting from amino olefins and aryl hydrazines is described. In a convergent manner, the two units bearing pharmacologically relevant substituents are assembled in the final indolization step. This modular and diversity-oriented approach to tryptamines and homotryptamines can be conducted in water and allows synthesis of branched and nonbranched tryptamines as well as tryptamine-based pharmaceuticals such as the 5-HT1D agonist L 775 606.
- Schmidt, Axel M.,Eilbracht, Peter
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p. 5528 - 5535
(2007/10/03)
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- Anticonvulsant activity of semicarbazone derivatives of Mannich bases
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A series of semicarbazones of semicarbazide/p-chlorophenyl semicarbazide and Mannich bases of acetophenone/p-chloroacetophenone has been synthesized and their anticonvulsant activity screened against MES and scPTZ test. p-Chlorophenyl semi-carbazone of N,N-dimethylaminopropiophenone has been found to be the most active in all these tests.
- Pandeya,Sowmyalakshmi,Panda,Pandeya,Stables
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p. 2657 - 2661
(2007/10/03)
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- Simple synthetic equivalents for the β-(N,N-disubstituted)ethylamino acyl cation synthon and their applications
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Various N,N-disubstituted-β-amino-N-methoxy-N-methylpropanamides 3a-i were prepared which served as an excellent β-aminoacyl cation equivalents. These were used to prepare β-amino ketones 1, pharmacologically active tertiary 1-(3,3-diarylpropyl)amines 7a-c, and the interesting C-glycoside 8.
- Selvamurugan,Aidhen
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p. 2239 - 2246
(2007/10/03)
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- Direct synthesis of β-aminoketones from amides via novel sequential nucleophilic substitution/Michael reaction
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(formula presented) The synthesis of β-aminoketones from amides can be achieved in a process consisting of sequential nucleophilic substitution at the carbonyl group by vinylmagnesium bromide followed by Michael reaction after quench of the first reaction
- Gomtsyan, Arthur
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- Hypolipidemic effects of α, β, and γ-alkylaminophenone analogs in rodents
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A number of N-substituted β-alkylaminophenone derivatives including two (α- and two γ-alkylaminophenone analogs were synthesized and investigated for hypolipidemic activity in mice at 8 mg/kg/day ip. Most of these analogs were found to be significantly more active than lovastatin and clofibrate. N-Phenylpiperazinopropiophenone 16 was one of the best derivatives, lowering serum cholesterol levels 41% and serum triglyceride levels 48% after 16 days of drug administration in CF1 mice. In Sprague-Dawley rats, N-phenylpiperazinopropiophenone at 8 mg/kg/day orally also demonstrated more potent hypolipidemic activity than clofibrate, gemfibrozil, and lovastatin at their therapeutic dosage. It significantly reduced tissue cholesterol and triglyceride levels in the aorta wall tissue and lowered the cholesterol and triglyceride levels in chylomicron, very low density lipid (VLDL) and low density lipid (LDL) fractions, while it significantly elevated the cholesterol levels in high density lipid (HDL) fraction. This compound also proved to be active in lowering both cholesterol and triglyceride levels in hyperlipidemic mice and rats induced with atherogenic diet. In vitro liver acetyl coenzyme A (CoA) synthetase, 3-hydroxy-3-methyl glutaryl (HMG) CoA reductase, acyl CoA cholesterol acyl transferase (ACAT), sn-glycerol-3-phosphate acyltransferase, phosphatidylate phosphohydrolase, and hepatic lipoprotein lipase activities were significantly inhibited by N-phenylpiperazinopropiophenone from 25 to 100 μM.
- Huang,Hall
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p. 281 - 290
(2007/10/03)
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- Antivirally active N-cycloalkyl alkanol compounds
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The compounds are of the general formula or where R1 is -OH, amino or -SH, R2 is H, α- or β-naphthyl or optionally substituted phenyl, R3 is mono-, di- or tricycloalkyl of C6-16, optionally substituted, R4
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- Benzotriazole-assisted synthesis of novel mannich bases from ketones and diverse aldehydes
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A wide variety of β-amino ketones are prepared in moderate to good yields by the reaction of the lithium enolates of cyclohexanone, acetophenone, α-tetralone and camphor with the readily available adducts from an aldehyde or ketone, an amine and benzotriazole. Some diastereoselectivity is observed when the benzotriazole adduct is derived from benzaldehyde.
- Katritzky, Alan R.,Harris, Philip A.
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p. 987 - 996
(2007/10/02)
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- A New Method of α-Functionalization for Tertiary Amines by Nucleophilic Substitution of α-Siloxy Amines
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α-Siloxy amines, which were easily prepared by "silicon Polonovski reaction" of tertiary amine N-oxides with trialkylsilyl trifluoromethanesulfonate, were treated with various nucleophiles to give the corresponding α-functionalized tertiary amines in moderate to good yields.This new method has to the advantage that it enables the α-substitution of amines not only by alkyl groups but also by alkenyl and aryl groups with sp2 carbon as a reaction center, since the introduction of such groups is difficult in electrophilic substitution of dipole-stabilized α-lithio amines.Besides the organometallics such as Grignard and organoaluminum reagents, trimethylsilyl cyanide and silyl enol ether could also be employed as nucleophiles in the presence of an appropriate Lewis acid.
- Tokitoh, Norihiro,Okazaki, Renji
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p. 735 - 740
(2007/10/02)
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- EFFECT OF THE STRUCTURE OF THE REAGENTS ON THE FORMATION RATE OF ARYL VINYL KETONES IN THE REACTION OF AMINES WITH β-HALOGENOPROPIOPHENONES
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The dependence of the formation rate of aryl vinyl ketones in the reaction of ring-substituted β-halogenopropiophenones with various amines on the structure of the reagents was investigated.By analysis of the obtained data it was concluded that the process takes place by an E2 mechanism through an anion-like transition state.
- Popov, A. F.,Piskunova, Zh. P.,Matvienko, V. N.
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p. 1918 - 1921
(2007/10/02)
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- KINETICS AND MECHANISM OF REACTION OF AMINES WITH β-BROMOPROPIOPHENONE
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The reaction of β-bromopropiophenone with different amines in acetonitrile at 25 deg C was studied.It was found that in the case of primary and secondary amines, the end products of the reaction are β-aminopropiophenones, which form via the intermediate phenyl vinyl ketone.In the case of tertiary amines, the reaction ends at the stage of the formation of phenyl vinyl ketone.The reactivity of the amines in the formation of phenyl vinyl ketone is preferentially determined by their basicity.
- Popov, A. F.,Piskunova, Z.,Matvienko, V. N.
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p. 1299 - 1302
(2007/10/02)
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