- New 1,3-dioxolane and 1,3-dioxane derivatives as effective modulators to overcome multidrug resistance
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Multidrug resistance (MDR) to antitumor agents represents a major obstacle to a successful chemotherapy of cancer. Overexpression of P-glycoprotein (p-gp) seems to be the major factor responsible for MDR. A large number of chemically unrelated compounds are known to interact with p-gp resulting in a decreasing resistance. In our efforts related to structure-activity studies of new potential MDR reversal agents we synthesized a series of compounds that differ in the aromatic core structure, the linker, and the basic moiety. For our search of new aromatic core structures we synthesized novel 2,2-diphenyl-1,3-dioxolane, 2,2- diphenyl-1,3-dioxane, and 4,5-diphenyl-1,3-dioxolane derivatives. A range of lipophilic linker structures and protonable basic moieties were synthesized and investigated to optimize the structure of the potential MDR-modulators. The compounds were tested in vitro using human Caco-2 cells. Both the cytotoxicity of the synthons and their ability to resensitize the cells were determined with a MTT assay. The results show that at low concentration various substances reverse tumor cell MDR. Some of the new structures show better effects than established modulators like trifluoperazine.
- Schmidt, Matthias,Ungvari, Johannes,Gloede, Julia,Dobner, Bodo,Langner, Andreas
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p. 2283 - 2297
(2007/10/03)
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- SIP3 RECEPTOR ANTAGONIST
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PROBLEM TO BE SOLVED: To obtain a compound having selective SIP3 receptor antagonism and a medicine containing the same. SOLUTION: The medicine comprises an aminopropionic acid derivative represented by general formula (1) (R1 is a hydrogen atom or a lower alkyl group; R2 is formula A; A is CO or CH2; E is an oxygen atom or an NR4; R3 is a lower alkyl group or formula B; G is CH, a nitrogen atom or a phosphorus atom; J is an oxygen atom or a sulfur atom; R4 is a hydrogen atom or a lower alkyl group; R5, R6 and R7 are each the same or different and a hydrogen atom, a lower alkyl group, a lower alkoxy group, a halogen atom, a nitro group or a haloalkyl group; m is an integer of 1-8; n is an integer of 1-5) or its pharmaceutically permissible salt as an active ingredient.
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Page/Page column 20
(2010/02/14)
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- Reduction of activated thiopyridyl compounds by zinc metal
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Starting from thiopyridyl compounds bearing a radical stabilizing group in α-position to the thiopyridyl moiety, the thiopyridyl group can be easily removed upon reduction by zinc metal in acetic acid.
- Boivin, Jean,Lallemand, Jean-Yves,Schmitt, Andreas,Zard, Samir Z.
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p. 7243 - 7246
(2007/10/02)
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