- The evaluation of 1-tetralone and 4-chromanone derivatives as inhibitors of monoamine oxidase
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Abstract: Monoamine oxidase (MAO) is of much clinical relevance, and inhibitors of this enzyme are used in the treatment for neuropsychiatric and neurodegenerative disorders such as depression and Parkinson’s disease. The present study synthesises and evaluates the MAO inhibition properties of a series of 33 1-tetralone and 4-chromanone derivatives in an attempt to discover high-potency compounds and to expand on the structure–activity relationships of MAO inhibition by these classes. Among these series, eight submicromolar MAO-A inhibitors and 28 submicromolar MAO-B inhibitors are reported, with all compounds acting as specific inhibitors of the MAO-B isoform. The most potent inhibitor was a 1-tetralone derivative (1h) with IC50 values of 0.036 and 0.0011?μM for MAO-A and MAO-B, respectively. Interestingly, with the reduction of 1-tetralones to the corresponding alcohols, a decrease in MAO inhibition potency is observed. Among these 1-tetralol derivatives, 1p (IC50 = 0.785?μM) and 1o (IC50 = 0.0075?μM) were identified as particularly potent inhibitors of MAO-A and MAO-B, respectively. Potent compounds such as those reported here may act as leads for the future development of MAO-B specific inhibitors. Graphic abstract: The present study describes the MAO inhibitory activities of a series of 1-tetralone and 4-chromanone derivatives. Numerous high-potency MAO-B specific inhibitors were identified.[Figure not available: see fulltext.].
- Cloete, Stephanus J.,N’Da, Clarina I.,Legoabe, Lesetja J.,Petzer, Anél,Petzer, Jacobus P.
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p. 491 - 507
(2020/10/02)
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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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supporting information
p. 1036 - 1040
(2021/02/09)
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- Preparation method of levobunolol hydrochloride
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The invention provides a preparation method of levobunolol hydrochloride. The preparation method comprises steps as follows: S-1-tert-butyl-epoxy methylamine and 1,2,3,4-tetrahydro-5-hydroxynaphthalen-1-one are subjected to a substitution reaction, and after acidizing treatment is performed, a target product, namely levobunolol hydrochloride, is prepared. With the adoption of the method, regioselectivity of the reaction is greatly improved, side reactions are avoided, yield of levobunolol hydrochloride is effectively increased, optical purity of levobunolol hydrochloride is effectively improved, yield reaches 87.3%, and ee value exceeds 99%.
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Paragraph 0041-0043-0044; 0048-0049; 0051-0052; 0054-0055
(2019/01/17)
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- A Radical-Based Synthesis of Lingzhiol
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The polycyclic natural product lingzhiol [(±)-1] was synthesized from dimethoxytetralone 8 via cyclization of an intermediate benzylic radical, generated from spiroepoxide 14, onto an alkynyl substituent generating tetracyclic compound 13 with an exocyclic double bond. After oxidative cleavage of the double bond of 13 and reduction of the keto function of 23, the correct diastereomer, 12-syn, was converted to lingzhiol (1) via known steps. In a similar manner, lingzhiol analogue 39 was synthesized from 5-methoxy-1-tetralone (27).
- Mehl, Lea-Marina,Maier, Martin E.
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supporting information
p. 9844 - 9850
(2017/09/23)
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- Enantioselective halogenative semi-pinacol rearrangement: Extension of substrate scope and mechanistic investigations
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The present Full Paper article discloses a survey of our recent results obtained in the context of the enantioselective halogenation-initiated semi-pinacol rearrangement. Commencing with the fluorination/semi-pinacol reaction first and moving to the heavier halogens (bromine and iodine) second, the scope and limitations of the halogenative phase-transfer methodology will be discussed and compared. An extension of the fluorination/semi-pinacol reaction to the ring-expansion of five-membered allylic cyclopentanols will be also described, as well as some preliminary results on substrates prone to desymmetrization will be given. Finally, the present manuscript will culminate with a detailed mechanistic investigation of the canonical fluorination/semi-pinacol reaction. Our mechanistic discussion will be based on in situ reaction progress monitoring, complemented with substituent effect, kinetic isotopic effect and non-linear behaviour studies.
- Romanov-Michailidis, Fedor,Romanova-Michaelides, Maria,Pupier, Marion,Alexakis, Alexandre
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supporting information
p. 5561 - 5583
(2015/03/30)
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- Enantioselective organocatalytic fluorination-induced Wagner-Meerwein rearrangement
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Cracked under strain: Strained allylic cyclobutanols and cyclopropanols readily undergo a ring expansion described by the title rearrangement. This reaction is promoted by catalytic amounts of 1 and displays high tolerance with respect to the substrate scope. The corresponding β-fluoro spiroketone products are isolated in high yields and with excellent stereoselectivities. EDG=electron-donating group, EWG=electron-withdrawing group. Copyright
- Romanov-Michailidis, Fedor,Guénée, Laure,Alexakis, Alexandre
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supporting information
p. 9266 - 9270
(2013/09/12)
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- Ferrocene tagged functional polymer: A robust solid-phase reagent for O-demethylation
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Ferrocene tagged functional polymer was synthesized by exploiting the propensity of the Merrifield resin to undergo quaternization with N-ferrocenylmethyl benzimidazole followed by subsequent anion metathesis reaction. The synthesized polymer when employed as a solid-phase reagent for O-demethylation of aryl methyl ethers, showed TON in the range of 7373-8930 and TOF in the range of 279-494 h-1.
- Kurane, Rajanikant,Gaikwad, Vipul,Jadhav, Jagannath,Salunkhe, Rajashri,Rashinkar, Gajanan
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p. 6361 - 6366,6
(2012/12/12)
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- BI-ARYL AMINOTETRALINES
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The invention is concerned with the compounds of formula I: and pharmaceutically acceptable salts and esters thereof, wherein R1-R5, A, B, Q, W, and X are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula I as well as pharmaceutical compositions containing such compounds. The compounds of formula I are antagonists at the CRTH2 receptor and may be useful in treating diseases and disorders associated with that receptor such as asthma.
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Page/Page column 18
(2010/03/04)
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- MONOARYL AMINOTETRALINES
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The invention is concerned with the compounds of formula I: and pharmaceutically acceptable salts and esters thereof, wherein R1, R2 and R3 are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula I as well as pharmaceutical compositions containing such compounds. The compounds of formula I are antagonists at the CRTH2 receptor and may be useful in treating diseases and disorders associated with that receptor such as asthma.
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Page/Page column 7; 23-24
(2010/03/04)
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- Cleavage of aromatic methyl ethers by chloroaluminate ionic liquid reagents
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We have discovered serendipitously that chloroaluminate ionic liquids can cleave aromatic methyl ethers under surprisingly mild conditions. Three ionic liquids, viz. [TMAH]-[Al2Cl7], [BMIM][Al2Cl7], and [EMIM][Al2Cl6I], and aluminum chloride were compared in the selective demethylation of 4,5-dimethoxyindanone at the 4-methoxy-function. The ionic liquids exhibited a remarkably high selectivity (96:4) in comparison with aluminum chloride (70:30). In addition, the reaction time was drastically shortened when the ionic liquids were used. Interestingly, the three ionic liquids displayed the same reactivity in the demethylation of 4,5-dimethoxyindanone. Considering the lower cost and the bulk availability of the precursors of [TMAH][Al2Cl7], we conclude that this is the most attractive ionic liquid from an industrial point of view. To make the large-scale application of [TMAH][Al2Cl7] feasible, we have developed a safe upscalable method for its preparation. Furthermore, the scope of ether cleavage by the ionic liquid reagent [TMAH][Al2Cl7] was investigated and it was found that aromatic methyl-, al- lyl-, and benzyl-ether cleavage is applicable to a variety of heterocyclic compounds. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Kemperman, Gerardus J.,Roeters, Theodorus A.,Hilberink, Peter W.
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p. 1681 - 1686
(2007/10/03)
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- Ionic hydrogenation of dihydroxynaphthalenes with cyclohexane in the presence of aluminum bromide
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Reactions of 1,5-, 1,6-, 1,7-, 2,6-, and 2,7-dihydroxynaphthalenes with cyclohexane in the presence of excess aluminum bromide in methylene bromide quantitatively yield 5-, 6-, and 7-hydroxynaphthalen-1-ones and 6- and 7-hydroxynaphthalen-2-ones, respectively. Tricationic C-protonated complexes are presumed to be reactive intermediates in these processes.
- Ostashevskaya,Koltunov,Repinskaya
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p. 1474 - 1477
(2007/10/03)
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- Acid-promoted fries rearrangements of benzannulated lactones
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The scope of acid-promoted Fries rearrangements of benzannulated lactones has been examined. The reaction is applicable to seven-membered lactones possessing a sufficiently activated aromatic ring but not to six-membered lactones, and it proceeds in higher yield for diterpenoid lactones than for lower molecular weight lactones. The structures of the 2,6-methano-bridged benzoxocin side products (23), (24), and (25) from rearrangement of the diterpenoid lactone (11) have been assigned.
- Cambie, Richard C.,Mitchell, Lorna H.,Rutledge, Peter S.
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p. 1167 - 1174
(2007/10/03)
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- Antimicrobial activity of 5,6-dihydrobenzo-[a]-carbazoles
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A new series of 5,6-dihydrobenzo[a]carbazoles was synthesized, some showing good antibacterial activity. The presence of a dialkylamino ethyl chain on the 2-, 3- or 4-O-substituent seems to be critical for such activity.
- Pappa,Segall,Pizzorno,Radice,Amoroso,Gutkind
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p. 333 - 336
(2007/10/02)
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- Studies on quinones. Part 22. Synthesis of 1-benzazepine-6,9-quinone derivatives
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A facile synthesis of 1,2,3,4-tetrahydro-5H-1-benzazepine-quinone derivatives starting from 5-methoxy-1-tetralone is described.
- Valderrama,Pessoa-Mahana,Tapia
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p. 629 - 639
(2007/10/02)
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- Titanium- or Zirconium-Catalyzed Selective Dehydrogenation of Benzyl Alcohols to Aldehydes and Ketones with tert-Butyl Hydroperoxide
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Primary and secondary benzyl alcohols are selectively converted in high yields into the corresponding aldehydes or ketones using tert-butyl hydroperoxides and catalytic amounts of titanium or (better) zirconium alcoholates.Aliphatic hydroxy groups, double bonds (except those in allylic position to hydroxy groups), and phenolic hydroxy groups (except those in the ortho position to the benzylic alcohol) are not attacked.
- Krohn, Karsten,Khanbabaee, Karamali,Rieger, Hagen
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p. 1357 - 1364
(2007/10/02)
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- Circulation-active novel substituted aminomethyl-5,6,7,8-tetrahydronaphthyloxy-acetic acids and intermediates therefor
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An aminomethyl-5,6,7,8-tetrahydronaphthyl-oxyacetic acid derivative of the formula STR1 in which R3 is aryl or substituted aryl, R2 is hydroxyl, alkoxy, phenoxy, benzoxy or NR4 R5, and R4 and R5 each independently is hydrogen or alkyl, or one of the radicals R4 or R5 is benzyl, and physiologically acceptable salts thereof with monovalent or divalent cations which have antithrombotic, antiatherosclerotic and antiischaemic activities.
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- HYDROXYLATION DU BENZALDEHYDE ET DE CETONES AROMATIQUES PAR LE PEROXYDE D'HYDROGENE EN MILIEU SUPERACIDE
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Benzaldehyde and aromatic ketones are hydroxylated by hydrogen peroxide in SbF5-HF without formation of products arising from Baeyer-Villiger oxidation.
- Gesson, Jean-Pierre,Jacquesy, Jean-Claude,Jouannetaud, Marie-Paule,Morellet, Guy
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p. 3095 - 3098
(2007/10/02)
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