70624-30-5Relevant articles and documents
Synthesis, evaluation and structural studies of antiproliferative tubulin-targeting azetidin-2-ones
O'Boyle, Niamh M.,Greene, Lisa M.,Bergin, Orla,Fichet, Jean-Baptiste,McCabe, Thomas,Lloyd, David G.,Zisterer, Daniela M.,Meegan, Mary J.
experimental part, p. 2306 - 2325 (2011/05/12)
A series of azetidin-2-ones substituted at positions 1, 3 and 4 of the azetidinone ring scaffold were synthesised and evaluated for antiproliferative, cytotoxic and tubulin-binding activity. In these compounds, the cis double bond of the vascular targeting agent combretastatin A-4 is replaced with the azetidinone ring in order to enhance the antiproliferative effects displayed by combretastatin A-4 and prevent the cis/trans isomerisation that is associated with inactivation of combretastatin A-4. The series of azetidinones was synthetically accessible via the Staudinger and Reformatsky reactions. Of a diverse range of heterocyclic derivatives, 3-(2-thienyl) analogue 28 and 3-(3-thienyl) analogue 29 displayed the highest potency in human MCF-7 breast cancer cells with IC50 values of 7 nM and 10 nM, respectively, comparable to combretastatin A-4. Compounds from this series also exhibited potent activity in MDA-MB-231 breast cancer cells and in the NCI60 cell line panel. No significant toxicity was observed in normal murine breast epithelial cells. The presence of larger, bulkier groups at the 3-position, for example, 3-naphthyl derivative 21 and 3-benzothienyl derivative 26, resulted in relatively lower antiproliferative activity in the micromolar range. Tubulin-binding studies of 28 (IC50 = 1.37 μM) confirmed that the molecular target of this series of compounds is tubulin. These novel 3-(thienyl) β-lactam antiproliferative agents are useful scaffolds for the development of tubulin-targeting drugs.
Acylaminothiazole derivatives, their preparation and their therapeutic use
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Page/Page column 9, (2008/06/13)
Compound corresponding to the general formula (I): in which, X represents an oxygen or sulphur atom; R1 represents a C1-10 alkyl group optionally substituted, a C3-7 cycloalkyl, thienyl, pyridinyl or pyrimidinyl group; the thienyl groups being optionally substituted; the phenyl group being optionally substituted; R2 represents a C1-6 alkyl group optionally substituted, a C3-7 cycloalkyl, piperidinyl, phenyl or pyridinyl group; the C3-7 cycloalkyl and piperidinyl groups being optionally substituted; the phenyl and pyridinyl groups being optionally substituted; R3 represents a hydrogen atom or a C1-6 alkyl group optionally substituted with a C3-7 cycloalkyl group; R4 represents a hydrogen atom or a C1-6 alkyl group; R5 and R5′ represent, independently of each other, a hydrogen or halogen atom, a hydroxyl or C1-3 alkyl group; or R5 and R5′ form together an oxo or oxime group such as: where R7 represents a hydrogen atom or a C1-3 alkyl; n represents an integer ranging from 0 to 3; and R6 represents, independently of each other when n=2 or 3, a hydrogen or halogen atom, a hydroxyl, C1-3 alkyl, C1-3 alkoxy, C1-3 fluoroalkyl or C1-3 fluoroalkoxy group; in the form of a base, of an addition salt with an acid, of a hydrate or of a solvate. therapeutic application.
Platelet activating factor antagonists: imidazopyridine indoles.
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, (2008/06/13)
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