1107635-38-0Relevant academic research and scientific papers
Synthesis and biological evaluation of 2-alkoxycarbonylallyl esters as potential anticancer agents
Ronayne, Conor T.,Solano, Lucas N.,Nelson, Grady L.,Lueth, Erica A.,Hubbard, Skyler L.,Schumacher, Tanner J.,Gardner, Zachary S.,Jonnalagadda, Sravan K.,Gurrapu, Shirisha,Holy, Jon,Mereddy, Venkatram R.
supporting information, p. 776 - 780 (2017/02/18)
The reaction of carboxylic acids with Baylis-Hillman reaction derived α-bromomethyl acrylic esters readily provide 2-(alkoxycarbonyl)allyl esters in good to excellent yields. These functionalized allyl esters have been evaluated for their cell proliferation inhibition properties against breast cancer (MDA-MB-231 and 4T1) and pancreatic cancer (MIAPaCa-2) cell lines to explore their potential as anticancer agents. Several of the synthesized derivatives exhibit good potency against all three cancer cell lines. Our structure activity relationship (SAR) studies on 2-carboxycarbonyl allyl esters indicate that substituted aromatic carboxylic acids provide enhanced activity compared to substituted aliphatic carboxylic acid analogs. Di- and tri-allyl esters derived from di-and tri-carboxylic acids exhibit higher inhibition of cell proliferation than mono esters. Further SAR studies indicate that the double bond in the 2-(alkoxycarbonyl)allyl ester is required for its activity, and there is no increase in activity with increased chain length of the alkoxy group. Two lead candidate compounds have been identified from the cell proliferation inhibition studies and their preliminary mechanism of action as DNA damaging agents has been evaluated using epifluorescence and western blot analysis. One of the lead compounds has been further evaluated for its systemic toxicity in healthy CD-1 mice followed by anticancer efficacy in a triple negative breast cancer MDA-MB-231 xenograft model in NOD-SCID mice. These two in vivo studies indicate that the lead compound is well tolerated in healthy CD-1 mice and exhibits good tumor growth inhibition compared to breast cancer drug doxorubicin.
Facile 1,3-diaza-Claisen rearrangements of tertiary allylic amines bearing an electron-deficient alkene
Aranha, Rachel M.,Bowser, Amy M.,Madalengoitia, Jose S.
supporting information; experimental part, p. 575 - 578 (2009/07/18)
(Chemical Equation Presented) Tertiary allylic amines with an electron-deficient alkene react with isocyanates and isothiocyanates to give highly substituted ureas and thioureas arising from formal 1,3-diaza-Claisen rearrangements. Isocyanates and isothiocyanates with strong electron-withdrawing groups are more reactive. Similarly, the data suggest that a stronger electron-withdrawing substituent on the alkene favors a faster reaction, but this may be offset by sterlcs in the cyclic transition state.
