- BF3-Et3O-mediated one-pot synthesis of acetylchromans from polyhydroxyacetophenones and isoprene/allyl alcohol
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A convenient one-pot method has been developed for the synthesis of substituted acetylchromans involving the condensation of polyhydroxyacetophenone with isoprene and long chain allylic alcohol (phytol) in the presence of borontrifluoride etherate (BF3-Et2O). Copyright Taylor & Francis Group, LLC.
- Narender,Reddy, K. Papi
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- Synthesis, crystal structure, conformational and vibrational properties of 6-acetyl-2,2-dimethyl-chromane
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The 6-acetyl-2,2-dimethyl-chromane compound was synthesized and characterized by IR, Raman, UV-Visible and 1H NMR spectroscopies. Its solid state structure was determined by X-ray diffraction methods. The substance crystallizes in the triclinic P-1 space group with a = 5.9622(5) ?, b = 10.342(1) ?, c = 10.464(1) ?, α = 63.81(1), β = 81.923(9), γ = 82.645(9), and Z = 2 molecules per unit cell. Due to extended π-bonding delocalization a substantial skeletal fragment of the molecule is planar. The vibrational modes were calculated at B3LYP/6-31G(d,p) level and all of them assigned in the IR and Raman spectra. The DFT calculated 1H NMR spectrum (chemical shifts) were in good agreement with the experimental data. The electronic (UV-Visible) spectrum was calculated using TD-DFT method in gas phase and it was correlated with the experimental data. The assignment and analysis of the frontier HOMO and LUMO orbitals indicate that the absorption bands are mainly originated from π → π * transitions. According to DSC measurements the substance presents a melting point of 93 C and decomposes at temperatures higher than 196 C.
- Lizarraga, Emilio,Gil, Diego M.,Echeverría, Gustavo A.,Piro, Oscar E.,Catalán, César A.N.,Ben Altabef, Aída
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- Combined 3D-QSAR and docking analysis for the design and synthesis of chalcones as potent and selective monoamine oxidase B inhibitors
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Monoamine oxidases (MAOs) are important targets in medicinal chemistry, as their inhibition may change the levels of different neurotransmitters in the brain, and also the production of oxidative stress species. New chemical entities able to interact selectively with one of the MAO isoforms are being extensively studied, and chalcones proved to be promising molecules. In the current work, we focused our attention on the understanding of theoretical models that may predict the MAO-B activity and selectivity of new chalcones. 3D-QSAR models, in particular CoMFA and CoMSIA, and docking simulations analysis have been carried out, and their successful implementation was corroborated by studying twenty-three synthetized chalcones (151–173) based on the generated information. All the synthetized molecules proved to inhibit MAO-B, being ten out of them MAO-B potent and selective inhibitors, with IC50 against this isoform in the nanomolar range, being (E)-3-(4-hydroxyphenyl)-1-(2,2-dimethylchroman-6-yl)prop-2-en-1-one (152) the best MAO-B inhibitor (IC50 of 170 nM). Docking simulations on both MAO-A and MAO-B binding pockets, using compound 152, were carried out. Calculated affinity energy for the MAO-A was +2.3 Kcal/mol, and for the MAO-B was ?10.3 Kcal/mol, justifying the MAO-B high selectivity of these compounds. Both theoretical and experimental structure–activity relationship studies were performed, and substitution patterns were established to increase MAO-B selectivity and inhibitory efficacy. Therefore, we proved that both 3D-QSAR models and molecular docking approaches enhance the probability of finding new potent and selective MAO-B inhibitors, avoiding time-consuming and costly synthesis and biological evaluations.
- Mellado, Marco,González, César,Mella, Jaime,Aguilar, Luis F.,Vi?a, Dolores,Uriarte, Eugenio,Cuellar, Mauricio,Matos, Maria J.
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- RAR-ALPHA COMPOUNDS FOR INFLAMMATORY DISEASE AND MALE CONTRACEPTION
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Modulators of retinoid acid receptor-alpha (RARα) of formula (I) are provided herein, as well as pharmaceutical compositions and methods relating thereto.
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- Identification of anticancer agents based on the thieno[2,3-b]pyridine and 1H-pyrazole molecular scaffolds
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Structural similarity search of commercially available analogues of thieno[2,3-b]pyridine and 1H-pyrazole derivatives, known anticancer agents, resulted in 717 hits. These were docked into the phosphoinositide specific-phospholipase C (PLC) binding pocket, the putative target of the compounds, to further focus the selection. Thirteen derivatives of the thieno[2,3-b]pyridines were identified and tested against the NCI60 panel of human tumour cell lines. The most active derivative 1 was most potent against the MDA-MB-435 melanoma cell line with GI50at 30?nM. Also, it was found that a piperidine moiety is tolerated on the thieno[2,3-b]pyridine scaffold with GI50?=?296?nM (MDA-MB-435) for derivative 10 considerably expanding the structure activity relationship for the series. For the 1H-pyrazoles four derivatives were identified using the in silico approach and additionally ten were synthesised with various substituents on the phenyl moiety to extend the structural activity relationship but only modest anticancer activity was found.
- Eurtivong, Chatchakorn,Reynisdóttir, Inga,Kuczma, Stephanie,Furkert, Daniel P.,Brimble, Margaret A.,Reynisson, Jóhannes
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p. 3521 - 3526
(2016/07/20)
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- Practical synthesis of a chromene analog for use as a retinoic acid receptor alpha antagonist lead compound
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Retinoic acid receptor alpha (RARα) selective compounds may guide the design of drugs that can be used in conjunction with hormonal adjuvant therapy in the treatment of breast cancer. Herein we report a modified synthesis of a known RARα antagonist, 2-fluoro-4-[[[8-bromo-2,2-dimethyl-4-(4- methylphenyl)chroman-6-yl]carbonyl]amino]benzoic acid and a synthesis of its unknown, desfluoro analog, 4-[[[8-bromo-2,2-dimethyl-4-(4-methylphenyl)chroman- 6-yl]carbonyl]amino]benzoic acid. The modified route allows for facile reaction workups, increased yields, lower cost and incorporates a green alternative step. Structure-activity relationship studies determined through functional cell-based assays, demonstrated antagonism to RARα for both compounds. Molecular modeling within the RARα binding pocket was used to compare binding interactions of the desfluoro analog to a known RAR antagonist.
- Jetson, Rachael,Malik, Neha,Luniwal, Amarjit,Chari, Venkatesh,Ratnam, Manohar,Erhardt, Paul
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p. 104 - 108
(2013/07/27)
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- Bi(OTf)3-catalysed prenylation of electron-rich aryl ethers and phenols with isoprene: A direct route to prenylated derivatives
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Electron-rich aryl ethers and phenols react with isoprene (2-methylbuta-1,3-diene) in the presence of catalytic Bi(OTf)3 at 40 °C to afford the corresponding prenylated or 2,2-dimethylchroman products, respectively, in moderate to good yields.
- Judd, Katie E.,Caggiano, Lorenzo
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supporting information; experimental part
p. 5201 - 5210
(2011/08/07)
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- Montmorillonite clays in organic synthesis: A one-pot conversion of phenols to 2,2-dimethylbenzopyrans
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2,2-Dimethylbenzopyran derivatives were generated through a one-pot Montmorillonite K10 clay-catalyzed condensation of substituted phenols with prenyl bromide.
- Dintzner, Matthew R.,McClelland, Kristen M.,Morse, Kara M.,Akroush, Michael H.
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p. 2028 - 2030
(2007/10/03)
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- Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities
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Aryl-substituted and aryl and (3-oxo-1-propenly)-substituted benzopyran, benzothiopyran, 1,2-dihydroquinoline, and 5,6-dihydronaphthalene derivatives have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action of RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists. For example, the retinoid negative hormone called AGN 193109 effectively increased the effectiveness of other retinoids and steroid hormones in in vitro transactivation assays. Additionally, transactivation assays can be used to identify compounds having negative hormone activity. These assays are based on the ability of negative hormones to down-regulate the activity of chimeric retinoid receptors engineered to possess a constitutive transcription activator domain.
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- Identification of highly potent retinoic acid receptor α-selective antagonists
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The syntheses and full retinoid receptor characterization of a novel series of retinoic acid receptor α (RARα) antagonists, 1-5, are described. These compounds bind with high affinity to RARα but were completely inactive in gene transactivation. They were also potent and effective antagonists of retinoic acid (RA) induced gene transcription at RARα. Compounds 1-5 exhibited varying degrees of selectivity for RARα relative to RARβ/γ, with compound 5 being the most selective in both binding and functional antagonism assays. These compounds will be invaluable tools in delineating the physiological roles of RARα in development and in the adult animal and may themselves be useful therapeutic agents in human diseases associated with RARα.
- Teng, Min,Duong, Tien T.,Johnson, Alan T.,Klein, Elliott S.,Wang, Liming,Khalifa, Berket,Chandraratna, Roshantha A. S.
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p. 2445 - 2451
(2007/10/03)
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- Benzopyran derivatives and heterocyclic analogs thereof as antiischemic agents
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A new method for the treatment of ischemic conditions and arrhythmia is disclosed. The method uses compounds of the formula STR1 wherein A can be --CH2 --, --O--, --NR9 --, --S--, --SO--, --SO2 --; X can be oxygen or sulfu
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- REGIOSELECTIVE PRENYLATION OF PHENOLS BY PALLADIUM CATALYST: SYNTHESES OF PRENYLPHENOLS AND CHROMANS
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The palladium-catalyzed coupling reaction of iodophenols (1) with 2-methyl-3-butyn-2-ol gave alkynylphenols (2).Catalytic hydrogenation of 2 over Raney nickel and the subsequent dehydration of the resultant alkylphenols (3) gave regioselectively the desired prenylphenols (4).Dehydration of alkylphenols (3f-h) gave chromans (7).
- Tsukayama, Masao,Kikuchi, Makoto,Kawamura, Yasuhiko
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p. 1487 - 1490
(2007/10/02)
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- Chroman esters of phenols and benzoic acids having retinoid-like activity
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Retinoid like activity is exhibited by compounds of the formula STR1 wherein the R 1 -R 7 groups are independently H or straight chain or branched chain lower alkyl or cycloalkyl of 1 to 6 carbons; X symbolizes an ester or thioester linkage, Y is cycloalk
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- Synthesis of 6-(1-Hydroxyethyl)-2,2-dimethyl-2H--benzopyrans: Eupatoriachromene-C and Desmethoxyencecalinol
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6-Acetyl-5,8-dimethoxy-2,2-dimethyl-2H--benzopyran (2) on reduction with potassium borohydride gives eupatoriochromene-C (1).Condensation of 4-Hydroxyacetophenone with isoprene in the presence of orthophosphoric acid gives the chroman (5) which on dehydrogenation with NBS furnishes desmethoxyencecalin (4). 4 on reduction with potassium borohydride affords desmethoxyencecalinol (3).Alternatively, 4-hydroxybenzaldehyde on condensation with isoprene gives the monochroman (6) which is also obtained by a similar condensation of 4-methylphenol with isoprene followed by reaction with DDQ.Dehydrogenation of 6 with NBS affords 6-formyl-2,2-dimethyl-2H--benzopyran (8) and 6-phenacyl bromide derivative (9). 8 on reaction with methylmagnesium iodide furnishes 3.
- Ahluwalia, V. K.,Mukherjee, Irani,Mukherjee, Keya
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p. 1124 - 1125
(2007/10/02)
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