180293-49-6Relevant 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.
A new method for production of chiral 2-aryl-2-fluoropropanoic acids using an effective kinetic resolution of racemic 2-aryl-2-fluoropropanoic acids
Tengeiji, Atsushi,Shiina, Isamu
experimental part, p. 7356 - 7378 (2012/09/05)
We report a new method for the preparation of chiral 2-aryl-2- fluoropropanoic acids, including 2-fluoroibuprofen, a fluorinated analogue of non-steroidal anti-inflammatory drugs (NSAIDs), by the kinetic resolution of racemic 2-aryl-2-fluoropropanoic acids using enantioselective esterification. By applying pivalic anhydride (Piv2O) as a coupling agent, bis(α-naphthyl)methanol [(α-Np)2CHOH] as an achiral alcohol, and (+)-benzotetramisole (BTM) as a chiral acyl-transfer catalyst, a series of racemic 2-aryl-2-fluoropropanoic acids were kinetically separated to afford the optically active carboxylic acids and the corresponding esters with good to high enantiomeric excesses. This technology can provide a convenient approach to furnish the chiral a-fluorinated drugs containing quaternary carbons at the α-positions in the 2-aryl-2-fluoropropanoic acid structure.
Electrochemical carboxylation of α,α-difluorotoluene derivatives and its application to the synthesis of α-fluorinated nonsteroidal anti-inflammatory drugs
Yamauchi, Yusuke,Fukuhara, Tsuyoshi,Hara, Shoji,Senboku, Hisanori
, p. 428 - 442 (2008/09/16)
Electrochemical carboxylation of α,α-difluorotoluene derivatives resulted in an efficient fixation of carbon dioxide to give the corresponding α-fluorophenylacetic acids in good yields, and this reaction was successfully applied to the synthesis of α-fluorinated nonsteroidal anti-inflammatory drugs (NSAIDs). Georg Thieme Verlag Stuttgart.
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.
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 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
Convenient routes to 2-aryl-2-fluoropropionic acids: Synthesis of monofluorinated analogues of (±)-ibuprofen, (±)-naproxen and related compounds
Goj, Olav,Kotila, Sirpa,Haufe, Guenter
, p. 12761 - 12774 (2007/10/03)
The synthesis of α-fluorinated arylpropionic acids 5 as analogues of the nonsteroidal anti-inflammatory agents (NSAIDs) flurbiprofen 1, ibuprofen 3 and naproxen 4 is accomplished by the oxidation of the corresponding primary alcohols 9. The latter are accessible on two different pathways showing their general applicability by variation of the aromatic moiety. Furthermore the influence of the fluorine substituent towards the conformation of the acid moiety in the crystal lattice is shown by comparative X-ray studies of compound 5c.
