- Deuterated Curcuminoids: Synthesis, Structures, Computational/Docking and Comparative Cell Viability Assays against Colorectal Cancer
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A series of deuterated curcuminoids (CUR) were synthesized, bearing two to six OCD3 groups, in some cases in combination with methoxy groups, and in others together with fluorine or chlorine atoms. A model ring-deuterated hexamethoxy-CUR–BF2 and its corresponding CUR compound were also synthesized from a 2,4,6-trimethoxybenzaldehyde-3,5-d2 precursor. As with their protio analogues, the deuterated compounds were found to remain exclusively in the enolic form. The antiproliferative activities of these compounds were studied by in vitro bioassays against a panel of 60 cancer cell lines, and more specifically in human colorectal cancer (CRC) cells (HCT116, HT29, DLD-1, RKO, SW837, and Caco2) and in normal colon cells (CCD841CoN). The deuterated CUR–BF2 adducts exhibited better overall growth inhibition by NCI-60 assay, while for other CUR–BF2 adducts the non-deuterated analogues were more cytotoxic. Results of the more focused comparative cell viability assays followed the same trend, but with some variation depending on cell lines. The CUR–BF2 adducts exhibited significantly higher cytotoxicity than CURs. Structural studies (X-ray and DFT) and computational molecular docking calculations comparing their inhibitory efficacy with those of known anticancer agents used in chemotherapy are also reported.
- Laali, Kenneth K.,Zwarycz, Angela T.,Bunge, Scott D.,Borosky, Gabriela L.,Nukaya, Manabu,Kennedy, Gregory D.
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p. 1173 - 1184
(2019/05/24)
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- HYDANTOIN CONTAINING DEOXYURIDINE TRIPHOSPHATASE INHIBITORS
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Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.
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Paragraph 0879
(2018/06/12)
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- A Mild meta-Selective C–H Alkylation of Catechol Mono-Ethers
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Catechol mono-ethers are an important class of phenols. They are found in a number of pharmaceuticals, flavoring agents, perfumes, and are used for the preparation of numerous drugs. Herein, we report a mild meta-selective C–H alkylation of these phenols, which is enabled by a cascade of oxidative dearomatization – radical addition – rearomatization process. The method is compatible with reactive functional groups on the parent arenol, such as olefins and halides. Primary, secondary, and teriary alkyl groups can be used, the source of which is most commonly an alkylborane. This process is operationally simple, does not require heating and generally proceeds in good yields.
- Vitaku, Edon,Njardarson, Jon T.
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supporting information
p. 3679 - 3683
(2016/08/16)
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- TETRAHYDROCYCLOPENTA[B]INDOLE ANDROGEN RECEPTOR MODULATORS
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The present invention provides a compound of the Formula (I), or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising a compound of Formula (I) in combination with a suitable carrier, diluent, or excipient; and methods for treating or preventing physiological disorders, particularly reduced bone mass, osteoporosis, osteopenia, reduced muscle mass or strength, or erectile dysfunction comprising administering a compound of Formula (I), or a pharmaceutically acceptable salt thereof.
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Page/Page column 38-39
(2009/12/23)
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- TRICYCLIC COMPOUND
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The present invention relates to tricyclic compounds each represented by the following formula (I): (wherein, R1, R2, R2', R3, R4, X, Y and Z have the same meanings as defined in the specification); and a drug containing the compound. Since the compounds according to the present invention exhibit an excellent squalene synthetase inhibitory effect and cholesterol synthesis inhibitory effect so that they are useful as a drug such as preventive and/or remedy for diseases in mammals including humans such as hyperlipemia, e.g., hypercholesterolemia, hypertriglyceridemia, and low HDL cholesterolemia and/or arteriosclerosis.
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Page/Page column 226
(2008/12/06)
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- 3-PHENOXY-4-PYRIDAZINOL DERIVATIVE AND HERBICIDE COMPOSITION CONTAINING THE SAME
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A compound represented by the formula: wherein R1 represents a hydrogen atom, a halogen atom, alkyl group, etc., ???R2 represents a hydrogen atom, a halogen atom, alkyl group, etc., ???R3, R4, R5, R6 and R7 each independently represent a hydrogen atom, a halogen atom, a substitutable alkyl group, a substitutable alkenyl group, alkynyl group, a substitute-able cycloalkyl group, etc., or adjacent two of R3, R4, R5, R6 and R7 may together with the carbon atoms to which the respective substituents are bonded form a ring which may be substituted, ???m and n each independently represent 0 or 1, a salt thereof or an ester derivative thereof; an agricultural chemical containing the same as an active ingredient; and a herbicidal composition containing the compound and a second herbicidally active compound as active ingredients.
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- Benzothienyloxy phenylpropanamines, novel dual inhibitors of serotonin and norepinephrine reuptake
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A series of benzothienyloxy phenylpropylamines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake. A series of benzothienyloxy propylamines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake.
- Boot,Brace,Delatour,Dezutter,Fairhurst,Findlay,Gallagher,Hoes,Mahadevan,Mitchell,Rathmell,Richards,Simmonds,Wallace,Whatton
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p. 5395 - 5399
(2007/10/03)
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- Unexpected Regioselectivity in the Lithiation of Fluoroanisoles
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The regioselectivity of lithiation of a series of fluoroanisoles and fluoroveratroles has been studied by determining the ratio of isomeric aldehydes produced by dimethylformamide quenching.The position of lithiation is influenced by such factors as temperature and time of the reaction.Contrary to published reports, fluorine competes significantly with the methoxy group as an ortho director in lithiation reactions.Lithiation of dimethyl-tert-butylsilyl ethers of fluorophenols proceeds exclusively ortho to fluorine.
- Furlano, David C.,Calderon, Silvia N.,Chen, George,Kirk, Kenneth L.
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p. 3145 - 3147
(2007/10/02)
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- Etude des complexes du cobalt (II) transporteurs d'oxygene: Nouvelle synthese du fluoro-3 hydroxy-2 benzaldehyde
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Synthetic chelates of cobalt (II) derived from Schiff bases have remarkable behavior of reversibly absorbing and releasing molecular oxygene.Among these, bis (3-fluorosalicylaldehydeethylenediimide) Co (II) (fluomine: Formula A, X=F) is most interesting in allowing to isolate pure oxygen from air, because it absorbs with extreme rapidity 4.43percent of its weight of oxygen.Fluomine is easily prepared from 3-fluorosalicylaldehyde (3FSA), ethylenediamine and cobalt (II) chloride; but substances such as 3-substituted salicylaldehydes have proven to be extremely difficult to prepare in other than small laboratory quantities from the corresponding ortho-substituted phenol.Many author have prepared 3-fluorosalicylaldehyde, as described in patents, but often these syntheses are very long and the yields are generally less than 20percent.We now describe a new synthesis from o-fluorophenol.Nitration of o-fluorophenol with liquid nitrogen dioxide is convenient: - on the one hand, ortho-substitution to the hydroxyl group, is easy, -on the other hand, the para substituted by-product, is reinserted in the course of the synthesis, so that it is possible to minimize loss of the starting phenol, an expensive product. o-Fluorophenol 1 in solution in pentane, at about 0 deg C, is treated with liquid nitrogen dioxide (slight excess).The reaction is rapid and leads to 2-fluoro 6-nitrophenol 2 which remains in solution, and 2-fluoro 4-nitrophenol 7 which cristallizes rapidly (approximatively 50percent of each one). 2-Fluoro 6-nitrophenol 2 is converted into the anisole 3, the NO2 group of which is catalytically reduced by hydrogen into 3-fluoro 2-methoxy-aminobenzene 4.This amine 4 is diazotized, and treated with formaldoxime to lead to 3-fluoro 2-methoxybenzaldehyde 5 (Eb12 = 82 deg C). 3FSA is finally obtained by heating under reflux anisole 5 and a solution of hydrobromic acid (48percent). 2-Fluoro 4-nitrophenol 7 is converted in five steps into 3-fluoro 2-methoxyaminobenzene 4 by the same reactions as these used for its isomer.Finally the total yield of amine 4 from o-fluorophenol is 73percent, and 3FSA is obtained in 25percent yield.No primary amines are required during the isolation, so that no possible contamination of the final product is possible and therefore the fluomine prepared therefrom is not contaminated and deactivated.
- Aymes, Daniel J.,Paris, Michel R.
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p. 175 - 178
(2007/10/02)
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