- 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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- Fluoxetine scaffold to design tandem molecular antioxidants and green catalysts
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Fluoxetine finds application in the treatment of depression and mood disorders. This selective serotonin-reuptake inhibitor (SSRI) also contrasts oxidative stress by direct ROS scavenging, modulation of the endogenous antioxidant defense system, and/or enhancement of the serotonin antioxidant capacity. We synthesised some fluoxetine analogues incorporating a selenium nucleus, thus expanding its antioxidant potential by enabling a hydroperoxides-inactivating, glutathione peroxidase (GPx)-like activity. Radical scavenging and peroxidatic activity were combined in a water-soluble, drug-like, tandem antioxidant molecule. Selenofluoxetine derivatives were reacted with H2O2in water, and the mechanistic details of the reaction were unravelled combining nuclear magnetic resonance (NMR), electrospray ionisation-mass spectrometry (ESI-MS) and quantum chemistry calculations. The observed oxidation-elimination process led to the formation of seleninic acid and cinnamylamine in atrans-selective manner. This mechanism is likely to be extended to other substrates for the preparation of unsaturated cinnamylamines.
- Bortoli, Marco,Gianoncelli, Alessandra,Ongaro, Alberto,Orian, Laura,Oselladore, Erika,Ribaudo, Giovanni,Zagotto, Giuseppe
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p. 18583 - 18593
(2020/06/08)
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- SMALL MOLECULE CMKLR1 ANTAGONISTS IN INFLAMMATORY DISEASE
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α-NETA analogs are provided for the treatment of inflammatory disease.
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Paragraph 0201; 0264-0265; 0267
(2020/12/01)
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- 3-[(BENZO[D][1,3]DIOXOLAN-4-YL)-OXY]-3-ARYLPROPYLAMINE TYPE COMPOUNDS AND APPLICATIONS THEREOF
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The present invention relates to 3-[(benzo[d][1,3]dioxolan-4-yl)-oxy]-3-arylpropylamine compounds of formula I or pharmaceutically acceptable salts thereof and use thereof. The compound may be used to prepare an antidepressant agent.
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Paragraph 0066
(2018/02/02)
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- Probing the effect of heterocycle-bonding in PNX-type ruthenium pre-catalysts for reactions involving H2
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A series of ruthenium(ii) complexes with three novel PNX-type pincer ligands is reported, in which X denotes a heterocyclic donor group (PNX = Ph2PCH2CH2N(H)CH2-X, X = 2-pyridyl, 2-furanyl, 2-thiophenyl or 2-pyrrolyl). The reaction of [(Ph3P)3RuCl2] with one equivalent of ligand leads to the trans-dichloro complexes [(PNX)RuCl2(PPh3)] (1-4) for all ligands, whereas the complexation of [(Ph3P)3Ru(H)(Cl)(CO)] results in different types of complexes. The variation of the heterocyclic donor group is in line with different binding properties and a labilization of this group. Investigations on the catalytic activity of different types of ruthenium(ii) complexes in hydrogenation and dehydrogenation reactions reveal that more labile bound heterocycle donors result in a decrease of catalytic productivity and activity.
- Xu,Langer
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supporting information
p. 16785 - 16790
(2015/10/05)
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- Design of novel multiple-acting ligands towards SERT and 5-HT2C receptors
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This Letter describes our attempts to elaborate dually acting compounds possessing serotonin re-uptake transporter inhibitor and serotonin 5-HT 2C receptor antagonist properties. A novel series of 1,3-diphenylureas and N-phenylbenzamides have thus been prepared and evaluated. Based on its in vitro and in vivo activities, as well as pharmacokinetic profile, compound 16a was identified as a lead compound. The synthesis and structure-activity relationship of this series of compounds is presented herein.
- éliás, Olivér,ágai-Csongor, éva,Domány, Gy?rgy,Keseru, Gy?rgy Miklós,Gere, Anikó,Kiss, Béla,Hellinger, éva,Vastag, Mónika,Gyertyán, István
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p. 2118 - 2122
(2014/05/06)
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- Acid-catalyzed ether rearrangement: Total synthesis of isomimosifoliol and (±)-dihydromimosifoliol
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An acid-catalyzed rearrangement of benzyl phenyl ethers to diphenylmethane derivatives, followed by salt formation and Hofmann elimination, is a simple method for the syntheses of isomimosifoliol and dihydromimosifoliol.
- Arava, Veera Reddy,Malreddy, Sashibhushan,Thummala, Sreenivasulu Reddy
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p. 3545 - 3552,8
(2020/08/31)
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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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scheme or table
p. 3214 - 3226
(2010/10/19)
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- AN IMPROVED PROCESS FOR SYNTHESIZING HIGHLY PURE ATOMOXETINE
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The present invention relates to a process for the preparation of highly pure atomoxetine of formula (I) and pharmaceutically acceptable salts thereof Formula (I) The present invention also aims at novel processes for the preparation and purification of intermediates involved in the process of the present invention.
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Page/Page column 11
(2009/12/27)
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- INHIBITORS OF AKT ACTIVITY
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Invented are novel 1 H-imidazo[4,5-c]pyridin-2-yl compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.
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- Dutch Resolution: Separation of enantiomers with families of resolving agents. A status report
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Dutch Resolution is the term given to the use of mixtures (families) of resolving agents in classical resolutions. In this status report an overview is given of the latest results and new (possible) families of resolving agents are introduced. The concept of families is discussed as well as the factors that come into play on use of families. Practical aspects of Dutch Resolution in particular and resolutions in general are discussed.
- Kellogg, Richard M.,Nieuwenhuijzen, Jose W.,Pouwer,Vries, Ton R.,Broxterman, Quirinus B.,Grimbergen, Reinier F.P.,Kaptein, Bernard,La Crois, Rene M.,De Wever, Ellen,Zwaagstra, Karen,Van Der Laan, Alexander C.
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p. 1626 - 1638
(2007/10/03)
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- Duloxetine (Cymbalta), a dual inhibitor of serotonin and norepinephrine reuptake.
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A series of naphthalenyloxy-arylpropylamines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake. One member of this series, duloxetine (Cymbalta) has proven to be effective in clinical trials for the treatment of depression.
- Bymaster,Beedle,Findlay,Gallagher,Krushinski,Mitchell,Robertson,Thompson,Wallace,Wong
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p. 4477 - 4480
(2007/10/03)
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- S(N)Ar reactions of 2-haloarylsulfoxides with alkoxides provide a novel synthesis of thiotomoxetine
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A five step synthesis of thiotomoxetine (2) is described. Installation of the aryl ether was accomplished using a highly efficient S(N)Ar fragment coupling between amino alcohol (4) and a 1-halo-2-methylsulfinylbenzene (X = F or Cl) followed by a selective reduction of the arylsulfoxide moiety.
- Ratz, Andrew M.,Weigel, Leland O.
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p. 2239 - 2242
(2007/10/03)
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- 2-(3-phenylpropyl)hydrazines and method of treating personality disorders
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Novel 2-(3-phenylpropyl)hydrazines, intermediates in and processes for the preparation thereof, and a method of treating personality disorders utilizing compounds or compositions thereof are disclosed.
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- Aryloxyphenylpropylamines and their preparation and use
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Novel aryloxyphenylpropylamines having the formula STR1 wherein R1 is C3-7 -cycloalkyl, C3-10 -alkyl, or alkenyl which may be straight, branched or cyclic, unsubstituted or substituted with C1-4 -alkoxy, aryloxy or cycloalkyl or cycloalkylalkyl; and R2 is 3,4-methylenedioxyphenyl, aryl or heteroaryl, which are optionally substituted with one or more cyano, halogen, C1-6 -alkyl, C1-6 -alkoxy, C1-6 -alkenyl, trifluoromethyl, C3-5 -alkylene, aryloxy or aralkoxy and a salt thereof with a pharmaceutically acceptable acid. The novel compounds are useful in the treatment of anoxia, migraine, ischemia and epilepsy.
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- Hydride Transfer Reaction Products in the Aminomethylation of Styrene
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Aminomethylation of styrene with formaldehyde and dimethylamine leads to N-methylbenzenepropanamine (1), N-(3-phenylpropyl)benzenepropanamine (3), and α-methylenebenzenepropanal (4) as major products.The ratio of 1, 3 and 4 is considerably influenced by the ratio of the reactants.The best yield of 1 is obtained by using dimethylamine in excess.Styrene in excess favors the formation of 3, and equivalent amounts of reactants afford the best yield of 4.Using formaldehyde in excess leads to the complete N-methylation of 1 and 3.When styrene reacts with formaldehyde and diethylamine or diisopropylamine the most important aminomethylation products are N-ethylbenzenepropanamine (11) or N-isopropylbenzenepropanamine (12), respectively, and 3 and 4 in both cases.The formation of the major products in the aminomethylation of styrene can be explained by the hydride transfer mechanism represented earlier as one competing mechanism for the aminomethylation of certain bicyclic alkenes.The N-methylation of amine 1 and 3, when formaldehyde is used in excess, is due to Eschweiler methylation under aminomethylation conditions.
- Manninen, Kalle,Karjalainen, Aira
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p. 190 - 195
(2007/10/02)
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- Treatment of obesity with aryloxyphenylpropylamines
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3-Aryloxy-3-phenylpropylamines and acid addition salts thereof are useful in blocking uptake of monoamines by brain neurons, and are thus effective in treating disorders of sleep, sexual performance, appetite, muscular function, and pituitary function.
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- Kinetic Resolution of Racemic β-Hydroxy Amines by Enantioselective N-Oxide Formation
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A practical and fairly general procedure for the kinetic resolution of β-hydroxy tertiary amines is described.It involves the selective oxidation of one enantiomer to the N-oxide by using tert-butyl hydroperoxide (TBHP) and a chiral catalyst prepared by mixing 2 parts of titanium isopropoxide (Ti(O-i-Pr)4 and 1.2 parts of either (+)- or (-)-diisopropyl tartrate (DIPT).The product N-oxide and the unreacted amino alcohol are then easily separated by trituration or organic/aqueous solvent extractions, and chromatography is avoided.The oxidations are generally run to 60percent conversion and the results for 21 different amino alcohols are given.The enantiomeric excess of the slow reacting (i.e., recovered) enantiomer of the amino alcohol often exceeds 90percent.Among the more interesting substrates are the natural product ubine (95percent ee) (18), N-methylephedrine (95percent ee) (15), N-methylpseudoephedrine (93percent ee) (16), cis-2-(dimethylamino)cyclohexanol (>95percent ee) (13), trans-2-(dimethylamino)cyclohexanol (92percent ee) (12), N-benzylbevantolol (85percent ee) (27), and N-benzylpropranolol (32percent ee) (21).The latter two examples are β-blocker precursors.One of the most important characteristics of this new route to enantiomerically pure β-hydroxy amines is its predictability.Thus, in all cases examined to date, when using (+)-DIPT the absolute configuration at the carbinol center in the slow reacting enantiomer is always the same .A study of how the titanium/tartrate ratio, water, catalyst/substrate ratio, and temperature effect this reaction is discussed.
- Miyano, Sotaro,Lu, Linda D.-L.,Viti, Steven M.,Sharpless, K. Barry
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p. 4350 - 4360
(2007/10/02)
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- 1-PIPERAZINES AND SOME RELATED COMPOUNDS
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Amino alcohols VIIIa-c, prepared by reduction of the Mannich bases VIa-c, were transformed by treatment with thionyl chloride to the chloro derivatives IXa-c which were subjected to substituttion reactions with the sodium salts of guaiacol, 2-ethoxyphenol and 2-benzyloxyphenol giving the title compounds IIIb,c, IVb,c and Va-c.N,N-Dimethyl-3-(2-benzyloxyphenoxy)-3-phenylpropylamine (Va) was partially demethylated by treatment with ethyl chloroformate and by the following alkaline hydrolysis to the secondary amine XI.Amines III-V and XI in high doses exhibit centralexcitation but do not show antireserpine activity; they have several structurally less specific effects (hypotensive, local anaesthetic, spasmolytic).
- Valenta, Vladimir,Bartosova, Marie,Protiva, Miroslav
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p. 1280 - 1287
(2007/10/02)
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- AMINO ALCOHOL DERIVATIVES: EFFECTS OF ALCOHOL METABOLISM ENZYMES
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A number of amino alcohols have been synthesized as part of the search for effective chemotherapeutic agents for alcoholism; their effects on the activity of enzymes involved in alcohol metabolism - alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) - have been investigated.
- Libinzon, R. E.,Shchors, E. I.,Allakhverdiev, M. A.,Cherkasova, E. M.
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p. 695 - 699
(2007/10/02)
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- Transformation of Acyclic Ketones into Aldehydes and Ketones with Substituted Side Chains
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Aminomethylation of the acyclic ketones 1/2 leads to the aminoketones 3/4 which give, after reduction, quaternisation and ion exchange or previous reaction with a Grignard reagent, the hydroxyammonium compounds 9/10 and 14, respectively.Flash thermolysis of 9/10 yields the aldehydes 7 and of 14 the ketone 15 in which one side-chain of the educt 2b is substituted by the alkyl group of the Grignard reagent.
- Tietze, Lutz-F.,Kinast, Guenther
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p. 451 - 460
(2007/10/02)
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- Aryloxyphenylpropylamines in treating depression
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3-Aryloxy-3-phenylpropylamines and acid additions salts thereof, useful as psychotropic agents, particularly as anti-depressants.
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