- BROMODOMAIN INHIBITORS FOR TREATING DISEASE
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Disclosed herein are compounds and compositions useful in the treatment of bromodomain-containing protein-mediated diseases, such as cancer, having the structure of Formula I: Methods of inhibiting activity of a bromodomain-containing protein in a human or animal subject are also provided.
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Paragraph 0226-0227
(2016/03/19)
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- Structural requirements of Dictyostelium differentiation-inducing factors for their stalk-cell-inducing activity in Dictyostelium cells and anti-proliferative activity in K562 human leukemic cells
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The differentiation-inducing factor-1 (DIF-1) is a lipophilic signal molecule (chlorinated alkylphenone) that induces stalk-cell differentiation in the cellular slime mould Dictyostelium discoideum. It has also been shown that DIF-1 and its derivative (DIF-3) suppress cell growth in mammalian tumor cells. In the present study, in order to assess the chemical structure-effect relationship of DIF derivatives and to develop useful agents for the study of both Dictyostelium development and cancer biology, we synthesized 28 analogues of DIF-1 and DIF-3 and investigated their stalk-cell-inducing activity in Dictyostelium HM44 cells (mutant strain) and anti-proliferative activity in human leukemia K562 cells. HM44 cells are defective in endogenous DIF-1 production and should be suitable for the assay for stalk-cell-inducing activity of DIF analogues. DIF-1 and some of its derivatives at nanomolar levels were good stalk-cell inducers in HM44 cells, whereas DIF-3 and some DIF-3 derivatives at micromolar levels were potent anti-proliferative agents in K562 cells. We also tried to search for antagonistic molecules against DIF-1 and DIF-3 but failed to find such molecules from the analogues used here. The present findings would give us hints for identifying the target molecule(s) of DIFs and also for developing novel anti-cancer drugs.
- Gokan, Naomi,Kikuchi, Haruhisa,Nakamura, Koji,Oshima, Yoshiteru,Hosaka, Kohei,Kubohara, Yuzuru
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p. 676 - 685
(2007/10/03)
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- Enol Ethers, XIV. Acylation of Keto Enol Ethers with Malonyl Dichloride - A New Synthesis of Phloroglucinols
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Phloroglucinols 4 and/or 4-hydroxy-2H-pyran-2-ones 5 are formed from keto enol ethers 1 and malonyl dichloride (2a) in high yields.Since the pyranones 5 can be smoothly converted into phloroglucinols, the reaction of 1 with 2a represents a new, facile synthetic route to phloroglucinols.The reaction proceeds via formation of a chloro carbonyl ketene 8 and its subsequent reaction with 1.The product ratio 4:5 is rationalized in terms of substituent effects in the enol ether substrate.
- Effenberger, Franz,Schoenwaelder, Karl-Heinz
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p. 3270 - 3279
(2007/10/02)
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- Process for preparing polyphenols
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Polyphenols of the general formula: STR1 wherein R represents a readily cleavable ether group and R' represents a hydrogen atom or a lower alkoxycarbonyl, such as the methoxycarbonyl or ethoxycarbonyl group, and of phloroglucinol, are made by heating a compound of the general formula: STR2 wherein R and R' have the same significance given above, with an alkali metal alcoholate and, if desired, converting the resulting compound of formula I into pholoroglucinol by ether-cleavage and removal of any ester group denoted by R' which may be present in accordance with methods known per se.
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