180293-53-2Relevant academic research and scientific papers
Inhibition of human α-methylacyl CoA racemase (AMACR): A target for prostate cancer
Carnell, Andrew J.,Kirk, Ralph,Smith, Matthew,Mckenna, Shane,Lian, Lu-Yun,Gibson, Robert
supporting information, p. 1643 - 1647 (2013/10/21)
The enzyme α-methylacyl CoA racemase (AMACR) is involved in the metabolism of branched-chain fatty acids and has been identified as a promising therapeutic target for prostate cancer. By using the recently available human AMACR from HEK293 kidney cell cultures, we tested a series of new rationally designed inhibitors to determine the structural requirements in the acyl component. An N-methylthiocarbamate (Ki=98nM), designed to mimic the proposed enzyme-bound enolate, was found to be the most potent AMACR inhibitor reported to date. Enolate mimicry: A range of inhibitors were designed and synthesized to determine the structural requirements for inhibition of the prostate cancer target racemase AMACR using the recently available human enzyme from HEK293 kidney cell cultures. An N-methylthiocarbamate (Ki=98nM), designed to mimic the proposed enzyme-bound enolate, is the most potent AMACR inhibitor reported to date.
On the enzymatic hydrolysis of methyl 2-fluoro-2-arylpropionates by lipases
Bellezza, Francesca,Cipiciani, Antonio,Ricci, Giacomo,Ruzziconi, Renzo
, p. 8005 - 8012 (2007/10/03)
The enzymatic hydrolysis of methyl 2-fluoro-2-arylpropionates was performed using lipases from Candida rugosa and Candida cylindracea (OF-360). A careful analysis of the reaction products revealed that racemic 2-hydroxy-2- arylpropionic acid and traces of 2-arylacrylic acid are formed, in addition to the expected 2-aryl-2-fluoropropionic acid. The presence of powerful electron-releasing groups in the aromatic ring of the substrate increase the amount of 2-hydroxypropionic acid. A mechanistic hypothesis has been formulated according to which the enzyme facilitates the elimination of fluoride ion from the hydrolysed acid with the formation of an α-carboxy-stabilized carbocation which provides 2-hydroxypropionic acids by nucleophilic attack of H2O and 2-arylacrylic acids by a β-elimination process.
Synthesis and optical resolution of 2-aryl-2-fluoropropionic acids, fluorinated analogues of Non-steroidal Anti-inflammatory Drugs (NSAIDs)
Fujisawa, Hidehito,Fujiwara, Tomoya,Takeuchi, Yoshio,Omata, Kenji
, p. 524 - 528 (2007/10/03)
We report the synthesis of optically active 2-aryl-2-fluoropropionic acids 2 as non-epimerizable mimics of 2-arylpropionic acids 1, a class of compounds which have been widely used as non-steroidal anti-inflammatory drugs (NSAIDs). This is a continuation of our research involving the design, synthesis, and evaluation of chiral fluorine-containing organic molecules as effective analogues of pharmacologically important compounds.
Synthesis of α-fluorocarboxylates from the corresponding acids using acetyl hypofluorite
Rozen,Hagooly,Harduf
, p. 7464 - 7468 (2007/10/03)
α-Fluorocarboxylic esters and acids were synthesized in good yields. The corresponding esters and acids were converted to their ketene acetals, and these enol derivatives reacted with AcOF made directly from fluorine. This route circumvents the problems associated with nucleophilic fluorinations such as various eliminations and rearrangements. α- and β-branched carboxylic acid derivatives that cannot be directly fluorinated gave by this electrophilic fluorination the corresponding α-fluoro derivatives in good yield. Both the fluorination reaction and the preparation of AcOF are fast and suitable for [18]F incorporation into acids and esters needed for working with PET. α-Fluoroibuprofen (20) and methyl 2-fluoro-3,3,3-triphenylpropionate (32) are two examples of this general reaction.
α-Fluoro analogues of inflammation inhibiting α-arylpropionic acids
Schlosser, Manfred,Michel, Dominique,Guo, Zhi-Wei,Sih, Charles J.
, p. 8257 - 8262 (2007/10/03)
2-Aryl-2-fluoropropionic acids were prepared by treatment of either ethyl α-hydroxy-carboxylates or cyanohydrin O-silyl ethers with diethylaminosulfur trifluoride and subsequent hydrolysis. The methyl ester of 2-fluoro-2-(4- isobutylphenyl)propionic acid
