- Efficient demethylation of aromatic methyl ethers with HCl in water
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A green, efficient and cheap demethylation reaction of aromatic methyl ethers with mineral acid (HCl or H2SO4) as a catalyst in high temperature pressurized water provided the corresponding aromatic alcohols (phenols, catechols, pyrogallols) in high yield. 4-Propylguaiacol was chosen as a model, given the various applications of the 4-propylcatechol reaction product. This demethylation reaction could be easily scaled and biorenewable 4-propylguaiacol from wood and clove oil could also be applied as a feedstock. Greenness of the developed methodversusstate-of-the-art demethylation reactions was assessed by performing a quantitative and qualitative Green Metrics analysis. Versatility of the method was shown on a variety of aromatic methyl ethers containing (biorenewable) substrates, yielding up to 99% of the corresponding aromatic alcohols, in most cases just requiring simple extraction as work-up.
- Bomon, Jeroen,Bal, Mathias,Achar, Tapas Kumar,Sergeyev, Sergey,Wu, Xian,Wambacq, Ben,Lemière, Filip,Sels, Bert F.,Maes, Bert U. W.
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supporting information
p. 1995 - 2009
(2021/03/26)
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- A metal-free method for the facile synthesis of indanonesviathe intramolecular hydroacylation of 2-vinylbenzaldehyde
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A facile method for the synthesis of indanones was developed under metal- and additive-free conditions, whereinl-proline served as an efficient and environmentally benign catalyst. Compared with previously synthesized indanones, synthesis by the transition-metal-catalyzed intramolecular hydroacylation of 2-vinylbenzaldehyde provided a more green synthetic pathway to indanone scaffolds with good to excellent yields. More importantly, it could be used to synthsize the anti-AD drug donepezil.
- He, Guoxue,Ma, Jinyu,Zhou, Jianhui,Li, Chunpu,Liu, Hong,Zhou, Yu
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p. 1036 - 1040
(2021/02/09)
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- Synthesis and antitumor activity of aza-brazilan derivatives containing imidazolium salt pharmacophores
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The synthesis of a series of novel aza-brazilan derivatives containing imidazolium salt pharmacophores is presented. The biological activity of such imidazolium salts was further evaluated in vitro against a panel of human tumor cell lines. The results suggest that the electron-withdrawing group on the aza-brazilan moiety, substituted 5,6-dimethyl-benzimidazole ring and substitution of the imidazolyl-3-position with a 4-methylbenzyl group were essential for modulating the cytotoxic activity. Compounds 55 and 39, bearing a 4-methylbenzyl substituent at position-3 of 5,6-dimethyl-benzimidazole, were found to be the most potent compounds with IC50 values of 0.52-1.30 μM and 0.56-1.51 μM against four human tumor cell lines investigated. Particularly, compound 57 exhibited inhibitory activity against the MCF-7 cell line with an IC50 value of 0.35 μM and was 56-fold more sensitive than DDP. Moreover, compound 55 inhibited cell proliferation through inducing G0/G1 cell cycle arrest and apoptosis in SMMC-7721 cells.
- Huang, Mingqin,Duan, Shengzu,Ma, Xueqiong,Cai, Bicheng,Wu, Dongmei,Li, Yan,Li, Liang,Zhang, Hongbin,Yang, Xiaodong
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supporting information
p. 1027 - 1036
(2019/06/27)
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- Trifluoroacetic Anhydride Mediated One-Pot Synthesis of 1-Aryl Isochroman-3-ones via the Carboxy-Pictet-Spengler Reaction
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In this paper, a novel and open-vessel route for the facile-operational synthesis of 1-aryl isochroman-3-ones is described via (CF3CO)2O (trifluoroacetic anhydride, TFAA)-mediated intermolecular (4 + 2) annulation of oxygenated arylacetic acids with arylaldehydes or ketones under mild reaction conditions. A plausible mechanism is proposed and discussed herein. Various reaction conditions are investigated for efficient transformation under an environmentally friendly one-pot carboxy-Pictet-Spengler reaction.
- Chang, Meng-Yang,Chen, Shin-Mei,Hsiao, Yu-Ting
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p. 11687 - 11698
(2019/10/02)
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- Synthesis of various arylated trifluoromethyl substituted indanes and indenes, and study of their biological activity
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A series of 1-trifluoromethyl substituted indanes and indenes bearing aryl groups in positions 1 and/or 3 of the indane core have been synthesized mainly by electrophilic cyclization and arylation of the corresponding trifluoromethylated allyl and propargyl alcohols. The distinctly lipophilic compounds thus obtained were tested against various components of human endocannabinoid system. None of the compounds displayed affinity toward CB1 or CB2 receptors. Two compounds inhibited monoacylglycerol lipase (MAGL) and three compounds showed inhibition of anandamide (AEA) uptake. The latter can be related to the low-micromolar inhibition of fatty acid amide hydrolase (FAAH) inhibition displayed by one of these compounds.
- Iakovenko, Roman O.,Chicca, Andrea,Nieri, Daniela,Reynoso-Moreno, Ines,Gertsch, Jürg,Krasavin, Mikhail,Vasilyev, Aleksander V.
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supporting information
p. 624 - 632
(2019/01/04)
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- Rigidification of a macrocyclic tris-catecholate scaffold leads to electronic localisation of its mixed valent redox product
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The catecholate groups in [{Pt(L)}3(μ3-tctq)] (H6tctq = 2,3,6,7,10,11-hexahydroxy-4b,8b,12b,12d-tetramethyltribenzotriquinacene; L = a diphosphine chelate) undergo sequential oxidation to their semiquinonate forms by voltammetry, with ΔE1/2 = 160-170 mV. The monoradical [{Pt(dppb)}3(μ3-tctq)]+ is valence-localised, with no evidence for intervalence charge transfer in its near-IR spectrum. This contrasts with previously reported [{Pt(dppb)}3(μ3-ctc)]+ (H6ctc = cyclotricatechylene), based on the same macrocyclic tris-dioxolene scaffold, which exhibits partly delocalised (class II) mixed valency.
- Greatorex, Sam,Vincent, Kevin B.,Baldansuren, Amgalanbaatar,McInnes, Eric J. L.,Patmore, Nathan J.,Sproules, Stephen,Halcrow, Malcolm A.
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supporting information
p. 2281 - 2284
(2019/02/27)
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- Two novel donepezil-lipoic acid hybrids: Synthesis, anticholinesterase and antioxidant activities and theoretical studies
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Alzheimer disease (AD) is a complex disease related to multiple pathogenic mechanisms. A strategy to develop effective drugs is based on the so-called multi-Target directed ligands (MTDL) by using hybrid compounds. So, in the present study, we have designed and synthesized two hybrids, containing the indanone-piperidine moiety of donepezil, a drug approved for the treatment of AD, and the lipoic acid scaffold, an antioxidant compound endowed with neuroprotective effects. One hybrid was synthesized in four steps with 42percent global yield, and the other hybrid in six steps with 19percent global yield. The latter hybrid displayed moderate inhibitory activity against human acetylcholinesterase (hAChE) and greater activity against human butyrylcholinesterases (hBuChE). The selectivity for hBuChE was further rationalized by theoretical study. Importantly, the second hybrid showed a good antioxidant activity, exhibiting better ability in scavenging 2,2-diphenyl- 1 picrylhydrazyl (DPPH) radicals than lipoic acid.
- Terra, Bruna S.,Da Silva, Pedro H. C.,Tramarin, Anna,Franco, Lucas L.,Da Cunha, Elaine F. F.,Macedo, Fernando,Ramalho, Teodorico C.,Bartolini, Manuela,Bolognesi, Maria L.,De Fátima, ?ngelo
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p. 738 - 747
(2018/02/07)
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- METHOD FOR PREPARING INDENOISOQUINOLINE DERIVATIVES
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A method for preparing indenoisoquinoline derivatives represented by the following formula (I) is disclosed, which comprises the following steps: (A) providing a first reactant represented by the following formula (II) and a second reactant represented by the following formula (III): wherein, R1, R3, A, X, Y, Z, m and n are defined in the specification; and (B) reacting the first reactant represented by the formula (II) and the second reactant represented by the formula (III) in a solvent and selectively adding R2NH2 therein, to obtain the indenoisoquinoline derivatives represented by the formula (I).
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Paragraph 0056
(2019/03/30)
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- Design, synthesis, molecular docking, and in vitro antidiabetic activity of novel PPARγ agonist
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Abstract: The present work describes the design, synthesis, molecular docking, biological evaluation, and assessment of structure–activity relationship of new derivatives based upon the molecular skeleton of the drug pioglitazone, a compound which is currently used for the management of type 2 diabetes mellitus. Pioglitazone has several side effects such as weight gain, edema, congestive heart failure, and bladder cancer. Therefore, there is a strong demand for identification of new lead candidates in the treatment of type 2 diabetes mellitus. A series of 24 compounds were prepared and evaluated for their peroxisome proliferator-activated receptor-γ (PPARγ) binding affinity assay and the IC50 values were determined. Among these compounds, six compounds exhibited promising IC50 values as compared to standard drugs pioglitazone and rosiglitazone. Furthermore, in order to confirm the target of these molecules, molecular docking study was carried out with peroxisome proliferator-activated receptor-γ (PPARγ) protein. Molecular modeling studies suggested that these compounds appropriately interact in the active sites of receptor. Graphical abstract: [Figure not available: see fulltext.].
- Chaturvedi, Radha Nandan,Pendem, Krishnaiah,Patel, Vipul P.,Sharma, Mukta,Malhotra, Sunita
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p. 2069 - 2084
(2018/08/22)
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- Design, synthesis and biological activity of 1H-indene-2-carboxamides as multi-targeted anti-Alzheimer agents
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The aim of this study was to design new molecules and evaluate their anticholinesterase and amyloid beta (Aβ1–42) inhibition activities as multifunctional drug candidates for the treatment of Alzheimer’s disease (AD). A series of 5,6-dimethoxy-1H-indene-2-carboxamides (1–22) was synthesized; cholinesterase inhibitory activities of the compounds were measured according to Ellman’s colorimetric assay, while the thioflavin T assay was used for measuring the inhibition of Aβ1–42 aggregation. The results revealed that most compounds showed higher inhibitory activity against BuChE than AChE. Compounds 20 and 21 were found to be the most potent BuChE inhibitors with respective IC50 values of 1.08 and 1.09 μM. Compounds 16, 20, 21 and 22 exhibited remarkable inhibition of Aβ1–42 aggregation. Kinetic analysis showed that the most potent BuChE inhibitor (20) acted as a noncompetitive inhibitor. Docking studies suggested that inhibitor 20 displayed many potential hydrogen-bondings with the PAS of BuChE. These results suggest that compound 20 may be an especially promising multifunctional drug for the prevention and treatment of AD.
- Koca, Mehmet,Yerdelen, Kadir Ozden,Anil, Baris,Kasap, Zeynep,Sevindik, Handan,Ozyurek, Ibrahim,Gunesacar, Gulsen,Turkaydin, Kubra
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- Design, Synthesis, and Evaluation of Donepezil-Like Compounds as AChE and BACE-1 Inhibitors
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An ecofriendly synthetic pathway for the synthesis of donepezil precursors is described. Alternative energy sources were used for the total synthesis in order to improve yields, regioselectively, and rate of each synthetic step and to reduce the coproduction of waste at the same time. For all products, characterized by an improved structural rigidity respect to donepezil, the inhibitor activity on AChE, the selectivity vs BuChE, the side-activity on BACE-1, and the effect on SHSY-5Y neuroblastoma cells viability were tested. Two potential new lead compounds for a dual therapeutic strategy against Alzheimers disease were envisaged.
- Costanzo, Paola,Cariati, Luca,Desiderio, Doriana,Sgammato, Roberta,Lamberti, Anna,Arcone, Rosaria,Salerno, Raffaele,Nardi, Monica,Masullo, Mariorosario,Oliverio, Manuela
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supporting information
p. 470 - 475
(2016/06/01)
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- Synthesis, characterization and nonlinear optical studies of novel blue-light emitting room temperature truxene discotic liquid crystals
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A new series of discotic liquid crystals based on a truxene core has been synthesized to study the structure-property relationship in view of the self-assembling property and their linear and nonlinear optical properties. All these branched alkyl chain truxene derivatives show a mesogenic property in a columnar hexagonal fashion at room temperature which is studied by a combination of different techniques. The newly synthesized truxene discotic 7a possesses a clearing temperature of 117 °C, one of the lowest clearing temperatures known in truxene discotic liquid crystals. We have discovered that the introduction of branching near to the core even in a small alkyl chain drastically reduces the isotropic temperature. Due to their C3 symmetry and their large first hyperpolarizability, these truxene derivatives show long-lived emissions in the solution state at room temperature. We also report large effective three-photon absorption in these materials under nanosecond laser pulse excitation at 532 nm, which makes them suitable candidates for optical limiting applications.
- Vinayakumara,Kumar, Manish,Sreekanth,Philip, Reji,Kumar, Sandeep
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p. 26596 - 26603
(2015/03/30)
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- Synthesis of donepezil-based multifunctional agents for the treatment of Alzheimer's disease
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Amyloid beta (Aβ) and cholinesterase enzymes (AChE, BuChE) are important biological targets for the effective treatment of Alzheimer's disease. In this study, the aim was to synthesize new donepezil-like secondary amide compounds that display a potent inhibition of cholinesterases and Aβ with antioxidant and metal chelation abilities. All test compounds showed activities against both ChEs and β1-42 inhibition. The most encouraging compound, 20, is an AChE inhibitor with high anti-aggregation activity (55.3%). Based on the results, compound 20 may be a promising structure in further research for new anti-Alzheimer's agents.
- Yerdelen, Kadir Ozden,Koca, Mehmet,Anil, Baris,Sevindik, Handan,Kasap, Zeynep,Halici, Zekai,Turkaydin, Kubra,Gunesacar, Gulsen
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supporting information
p. 5576 - 5582
(2015/11/17)
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- Synthesis, biological evaluation and mechanism study of a class of benzylideneindanone derivatives as novel anticancer agents
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A series of new benzylideneindanone derivatives were designed, synthesized and evaluated as antitumor agents. Structure-activity relationship (SAR) studies showed that derivatives with 4,5,6-trimethoxyl on an indanone moiety displayed good anti-proliferative activities. Especially, compound 5a demonstrated the most potent inhibitory activity, with GI50 values from 0.172 to 0.57 μM for five kinds of cancer cell lines. Further investigation showed that 5a could inhibit microtubule polymerization and thus induce G2/M phase arrest and apoptosis in A549 cells. Our findings revealed the benzylideneindanone moiety as a new attractive scaffold for mitosis-targeting drug discovery.
- Hu, Jinhui,Yan, Jun,Chen, Jie,Pang, Yanqing,Huang, Ling,Li, Xingshu
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p. 1318 - 1327
(2015/07/15)
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- Synthesis and anticancer activity of some 2-[3/4-(2-substituted phenyl-2-oxoethoxy)benzylidene]-6-substituted-2,3-dihydro-1H-inden-1-one derivatives
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The synthesis of 2-[3/4-(2-substituted phenyl-2-oxoethoxy)benzylidene]-6- substituted-2,3-dihydro-1H-inden-1-one derivatives and the investigation of their anticancer activity were studied. 2-(3- or 4-Hydroxybenzylidene)-6- substituted-2,3-dihydro-1H-inden-1-ones were reacted with suitable 2-bromoacetophenones to give 2-[3/4-(2-substituted phenyl-2-oxoethoxy) benzylidene]-6-substituted-2,3-dihydro-1H-inden-1-one derivatives. The structure elucidation of the synthesised compounds was performed by IR, 1H-NMR, mass spectroscopic data and elemental analyses. The anticancer screening was carried out in National Cancer Institute (NCI), USA. Notable activity was obtained for some compounds.
- Gundogdu-Karaburun, Nalan,Karaburun, Ahmet Cagri,Demirayak, Seref,Kayagil, Ismail,Yurttas, Leyla
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p. 578 - 585
(2014/05/20)
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- Non-conventional methodologies in the synthesis of 1-indanones
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1-Indanones have been successfully prepared by means of three different non-conventional techniques, namely microwaves, high-intensity ultrasound and a Q-tube reactor. A library of differently substituted 1-indanones has been prepared via one-pot intramolecular Friedel-Crafts acylation and their efficiency and "greenness" have been compared.
- Oliverio, Manuela,Nardi, Monica,Costanzo, Paola,Cariati, Luca,Cravotto, Giancarlo,Giofre, Salvatore Vincenzo,Procopio, Antonio
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p. 5599 - 5610
(2014/06/10)
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- Enantioselective total synthesis of (+)-brazilin, (-)-brazilein and (+)-brazilide A
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An enantioselective strategy for the synthesis of (+)-brazilin, (-)-brazilein and (+)-brazilide A has been developed. A Lewis acid mediated lactonization established the novel fused bis-lactone core of brazilide A and finalized the first total synthesis of (+)-brazilide A.
- Wang, Xuequan,Zhang, Hongbin,Yang, Xiaodong,Zhao, Jingfeng,Pan, Chengxue
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supporting information
p. 5405 - 5407
(2013/06/27)
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- Friedel-crafts acylation reactions using esters
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Intermolecular and intramolecular Friedel-Crafts acylation reactions of various aliphatic and aromatic esters at room temperature with the use of very simple reagents and activating groups in are described. The products were obtained in good yield (60-85 %). The detailed mechanistic pathway was studied by DFT calculations and supported by experimental evidence. Copyright
- Chavan, Subhash P.,Garai, Sumanta,Dutta, Achintya Kumar,Pal, Sourav
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p. 6841 - 6845
(2013/02/22)
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- Design and synthesis of brazilin-like compounds
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A general and flexible synthetic route, which leads to the synthesis of brazilin-like compounds, was developed. The aza-brazilin derivatives show strong anticancer activities in MTT assay towards a number of human cancer cell lines including HT29, A549, HL60, and K562. Georg Thieme Verlag Stuttgart New York.
- Pan, Chengxue,Zeng, Xianghui,Guan, Yifu,Jiang, Xiangliu,Li, Liang,Zhang, Hongbin
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supporting information; experimental part
p. 425 - 429
(2011/04/22)
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- Inter- and intramolecular hydroacylation of alkenes employing a bifunctional catalyst system
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Based on a conceptually innovative bifunctional P,N ligand, an efficient protocol for the rhodium-catalyzed inter- and intramolecular hydroacylation of alkenes has been developed.
- Vautravers, Nicolas R.,Regent, Damien D.,Breit, Bernhard
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supporting information; experimental part
p. 6635 - 6637
(2011/06/27)
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- PROCESS FOR PRODUCTION OF ALKOXYINDANONE DERIVATIVES
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[Problems to be Solved] The present invention aims to provide a method for efficiently producing a high-purity alkoxyindanone derivative while maintaining an industrially superior volumetric efficiency. [Solution] Provided is a method for producing an alkoxyindanone derivative represented by a general formula in Figure 2 (wherein R represents an alkoxy group containing 1 to 6 carbon atoms and n represents an integer of 1 to 4), comprising reacting an alkoxyphenylpropionic acid derivative represented by a general formula in Figure 1 (wherein R and n are as defined above) with a condensing agent, adding an organic solvent to the resulting reaction mixture, and subsequently decomposing the condensing agent with an aqueous alkaline solution.
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Page/Page column 8
(2010/09/05)
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- Highly chemoselective metal-free reduction of tertiary amides
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This communication describes the chemoselective metal-free reduction of tertiary amides to the corresponding amines. Hantzsch ester is used as a mild reducing agent for the reduction of trifluoromethanesulfonic anhydride activated amides providing the tertiary amines with high functional group tolerance. Copyright
- Barbe, Guillaume,Charette, Andre B.
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- Meldrum's acids as acylating agents in the catalytic intramolecular Friedel-Crafts reaction
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(Chemical Equation Presented) The intramolecular Friedel-Crafts acylation of aromatics with Meldrum's acid derivatives catalyzed by metal trifluoromethanesulfonates is reported. Meldrum's acids are easily prepared, functionalized, handled, and purified. The synthesis of polysubstituted 1-indanones from benzyl Meldrum's acids was investigated thoroughly, and it was shown that a variety of catalysts were effective, while accommodating a diversity of functional groups under mild conditions. The scope, limitations, and functional group tolerance (terminal alkene and alkyne, ketal, dialkyl ether, dialkyl thioether, aryl methyl ether, aryl TIPS and TBDPS ethers, nitrile- and nitro-substituted aryls, alkyl and aryl halides) for a variety of 5-benzyl (enolizable Meldrum's acids) and 5-benzyl-5-substituted Meldrum's acids (quaternized Meldrum's acids), forming 1-indanones and 2-substituted-1- indanones, respectively, are delineated. This method was further applied to the synthesis of 1-tetralones, 1-benzosuberones, and the potent acetylcholinesterase inhibitor donepezil. Rate of cyclization as a function of ring size was established for various benzocyclic ketones via competition experiments: 1-tetralones form faster than both 1-indanones and 1-benzosuberones, and 1-benzosuberones cyclize faster than 1-indanones.
- Fillion, Eric,Fishlock, Dan,Wilsily, Ashraf,Goll, Julie M.
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p. 1316 - 1327
(2007/10/03)
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- Microwave-enhanced carbonylative generation of indanones and 3-acylaminoindanones
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(Chemical Equation Presented). The development of microwave-accelerated protocols for palladium(0)-catalyzed carbonylative cyclization of unsaturated aryl bromides and chlorides is described. By employing o-bromostyryl derivatives lacking substituents on the vinylic bond, molybdenum hexacarbonyl-mediated in situ carbonylation delivered a set of indan-1-one products in high yield after only 20 min of heating. Without the addition of the tri-tert-butylphosphine releasing Fu-salt ((t-Bu)3PHBF4), only incomplete conversions of sluggish o-styryl bromides and chlorides were realized. Internal and chemoselective palladium(0)-catalyzed Heck arylations of enamides afforded suitable starting materials for subsequent rapid ring-closing reactions. Microwave-heated intramolecular in situ carbonylation of these electron-rich and sterically congested olefins conveniently afforded eight functionalized 3-acylaminoindanone derivatives in a novel synthetic process. Attempted carbonylative annulation of electron-poor o-bromocinnamic acid derivatives furnished only the corresponding lactones via a competing hydroxycarbonylation- Michael addition reaction sequence.
- Wu, Xiongyu,Nilsson, Peter,Larhed, Mats
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p. 346 - 349
(2007/10/03)
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- Synthesis of 1-indanones by intramolecular Friedel-Crafts reaction of 3-arylpropionic acids catalyzed by Tb(OTf)3
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Intramolecular Friedel-Crafts acylation reaction of 3-arylpropionic acids was efficiently catalyzed by Tb(OTf)3 at 250°C to give 1-indanones. Even deactivated 3-arylpropionic acids with halogen atoms on the aromatic ring can be cyclized in moderation to good yields.
- Cui, Dong-Mei,Zhang, Chen,Kawamura, Masato,Shimada, Shigeru
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p. 1741 - 1745
(2007/10/03)
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- Palladium-catalyzed carbonylative cyclization of unsaturated aryl iodides and dienyl triflates, iodides, and bromides to indanones and 2-cyclopentenones
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Indanones and 2-cyclopentenones have been successfully prepared in good to excellent yields by the palladium-catalyzed carbonylative cyclization of unsaturated aryl iodides and dienyl triflates, iodides, and bromides, respectively. The best results are obtained by employing 10 mol % of Pd(OAc)2, 2 equiv of pyridine, 1 equiv of n-Bu4NCl, 1 atm of CO, a reaction temperature of 100 °C, and DMF as the solvent. This carbonylative cyclization is particularly effective on substrates that contain a terminal olefin. The proposed mechanism for this annulation includes (1) Pd(OAc)2 reduction to the active palladium(0) catalyst, (2) oxidative addition of the organic halide or triflate to Pd(0), (3) coordination and insertion of carbon monoxide to produce an acylpalladium intermediate, (4) acylpalladation of the neighboring carbon-carbon double bond, (5) reversible palladium β-hydride elimination and re-addition to form a palladium enolate, and (6) protonation by H2O to produce the indanone or 2-cyclopentenone.
- Gagnier, Steve V.,Larock, Richard C.
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p. 4804 - 4807
(2007/10/03)
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- Dopamine D3 receptor antagonists. 1. Synthesis and structure-activity relationships of 5,6-Dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans
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5,6-Dimethoxy-2-(N-dipropyl)-aminoindan (3, PNU-99194A) was found to be a selective dopamine D3 receptor antagonist with potential antipsychotic properties in animal models. To investigate the effects of nitrogen substitution on structure- activity relationships, a series of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans were synthesized and evaluated in vitro for binding affinity and metabolic stability. The results indicate that substitution at the amine nitrogen of the 2-aminoindans is fairly limited to the di-N-propyl group in order to achieve selective D3 antagonists. Thus, combinations of various alkyl groups were generally inactive at the D3 receptor. Although substitution with an N-alkylaryl or N-alkylheteroaryl group yields compounds with potent D3 binding affinity, the D2 affinity is also enhanced, resulting in a less than 4-fold preference for the D3 receptor site, and no improvements in metabolic stability were noted. A large-scale synthesis of the D3 antagonist 3 has been developed that has proven to be reproducible with few purification steps. The improvements include the use of 3,4-dimethoxybenzaldehyde as a low-cost starting material to provide the desired 5,6-dimethoxy-1-indanone 5c in good overall yield (65%) and the formation of a soluble silyl oxime 17 that was reduced efficiently with BH3·Me2S. The resulting amino alcohol was alkylated and then deoxygenated using a Lewis acid and Et3SiH to give the desired product 3 in good overall yield of (~65%) from the indanone 5c.
- Haadsma-Svensson,Cleek,Dinh,Duncan,Haber,Huff,Lajiness,Nichols,Smith,Svensson,Zaya,Carlsson,Lin
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p. 4716 - 4732
(2007/10/03)
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- Reaction of N,N-dimethylacrylamide/trifluoromethanesulfonic anhydride complex with electron-rich aromatic compounds
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The reaction of N,N-dimethylacrylamide/trifluoromethanesulfonic anhydride complex with electron-rich aromatic compounds affords after hydrolysis the corresponding indanones and 1,3-diarylpropanones.
- Nenajdenko, Valentine G.,Baraznenok, Ivan L.,Balenkova, Elizabeth S.
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p. 4199 - 4202
(2007/10/03)
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- N,N-dimethylacrylamide-triflic anhydride complex as a novel bifunctional electrophile in reaction with electron-rich aromatics
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The reaction of N,N-dimethylacrylamide/trifluoromethanesulfonic anhydride complex with alkoxybenzenes followed by hydrolysis leads to the corresponding indan-1-ones and 1,3-diarylpropan-1-ones. Substituted naphthalenes yield dihydrophenalen-1-ones. Fused ring aromatics afford aromatic amines.
- Nenajdenko, Valentine G.,Baraznenok, Ivan L.,Balenkova, Elizabeth S.
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p. 12993 - 13006
(2007/10/03)
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- Ring construction of several heterocycles with phosphorus pentoxide-methanesulfonic acid (PPMA)
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The cyclization reactions with CH3SO3H/P2O5 (PPMA) or CF3SO3H/P2O5 (PPTMA) at 80-100°C for 3-10 min afforded several heterocycles (6, 7-dihydropyrrolo[2, 3-c]azepin-4,8(1H, 5H)-dione, 4-oxo-4,5,6,7-tetrahydrothianaphthene, carbostyril derivatives).
- Cho, Hidetsura,Matsuki, Shinsuke
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p. 127 - 131
(2007/10/02)
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- Friedel-Crafts Acylation of Arenes Catalysed by Bromopentacarbonylrhenium(I)
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The intermolecular Friedel-Crafts acylation of aromatic compounds (such as toluene, m-xylene, and anisole) with various acid chlorides proceeds by using a catalytic amount of bromopentacarbonylrhenium(I) to afford aryl ketones.Intramolecular acylation is also catalyzed by the above-mentioned catalyst to give indanone and tetralone derivatives.
- Kusama, Hiroyuki,Narasaka, Koichi
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p. 2379 - 2384
(2007/10/03)
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- New Intramolecular Five-Endo-Mode Cyclization of Allenyl Aryl Ketones
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A convenient preparation of allenyl aryl ketones was achieved by the Weinreb-modified Grignard reaction of N-methoxy-N-methylamides with propargylmagnesium bromide.On treatment with BF3*OEt2, the allenyl aryl ketones were converted to methylenebenzocyclopentenones via a new 5-endo-mode cyclization.
- Nagao, Yoshimitsu,Lee, Woo-Song,Kim, Kweon
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p. 389 - 392
(2007/10/02)
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- An unusual C-C bond cleavage with chromium VI reagents: Oxidation of primary alcohols to ketones
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Oxidation of 1-hydroxymethylindanes and 1-hydroxymethyltetralins with PDC or PCC in methylene chloride affords 1-indanones and 1-tetralones.
- Bijoy,Subba Rao
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p. 2701 - 2708
(2007/10/02)
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- Antihypertensive tricyclic isoindole derivatives
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Tricyclic isoindole derivatives characterized by having a 1,2,3,4,6,10b-hexahydropyrazino[2,1-a]isoindole or 1,3,4,10b-tetrahydropyrimido[6,1-a]isoindol-6(2H)-one nucleus are disclosed. The foregoing compounds are useful antihypertensive agents.
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