1287264-24-7Relevant articles and documents
An inhibitor of fatty acid synthase thioesterase domain with improved cytotoxicity against breast cancer cells and stability in plasma
Lupien, Leslie E.,Dunkley, Evan M.,Maloy, Margaret J.,Lehner, Ian B.,Foisey, Maxwell G.,Ouellette, Maddison E.,Lewis, Lionel D.,Pooler, Darcy Bates,Kinlaw, William B.,Baures, Paul W.
supporting information, p. 171 - 185 (2019/11/02)
It is well recognized that many cancers are addicted to a constant supply of fatty acids (FAs) and exhibit brisk de novo FA synthesis. Upregulation of a key lipogenic enzyme, fatty acid synthase (FASN), is a near-universal feature of human cancers and their precursor lesions, and has been associated with chemoresistance, tumor metastasis, and diminished patient survival. FASN inhibition has been shown to be effective in killing cancer cells, but progress in the field has been hindered by off-target effects and poor pharmaceutical properties of candidate compounds. Our initial hit (compound 1) was identified from a high-throughput screening effort by the Sanford-Burnham Center for Chemical Genomics using purified FASN thioesterase (FASN-TE) domain. Despite being a potent inhibitor of purified FASN-TE, compound 1 proved highly unstable in mouse plasma and only weakly cytotoxic to breast cancer (BC) cells in vitro. An iterative process of synthesis, cytotoxicity testing, and plasma stability assessment was used to identify a new lead (compound 41). This lead is more cytotoxic against multiple BC cell lines than tetrahydro-4-methylene-2S-octyl-5-oxo-3R-furancarboxylic acid (the literature standard for inhibiting FASN), is stable in mouse plasma, and shows negligible cytotoxic effects against nontumorigenic mammary epithelial cells. Compound 41 also has drug-like physical properties based on Lipinski’s rules and is, therefore, a valuable new lead for targeting fatty acid synthesis to exploit the requirement of tumor cells for fatty acids.
Identification and SAR of Glycine Benzamides as Potent Agonists for the GPR139 Receptor
Dvorak, Curt A.,Coate, Heather,Nepomuceno, Diane,Wennerholm, Michelle,Kuei, Chester,Lord, Brian,Woody, David,Bonaventure, Pascal,Liu, Changlu,Lovenberg, Timothy,Carruthers, Nicholas I.
supporting information, p. 1015 - 1018 (2015/09/22)
A focused high throughput screening for GPR139 was completed for a select 100K compounds, and new agonist leads were identified. Subsequent analysis and structure-activity relationship studies identified (S)-3-chloro-N-(2-oxo-2-((1-phenylethyl)amino)ethyl
Stereodivergent synthesis of chiral fullerenes by [3 + 2] cycloadditions to C60
Maroto, Enrique E.,Filippone, Salvatore,Suarez, Margarita,Martinez-Alvarez, Roberto,De Cozar, Abel,Cossio, Fernando P.,Martin, Nazario
supporting information, p. 705 - 712 (2014/02/14)
A wide range of new dipoles and catalysts have been used in 1,3-dipolar cycloadditions of N-metalated azomethine ylides onto C60 yielding a full stereodivergent synthesis of pyrrolidino[60]fullerenes with complete diastereoselectivities and ver
Synthesis and separation of the enantiomers of the neuropeptide S receptor antagonist (9 R/S)-3-Oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4- a ]pyrazine-7-carboxylic Acid 4-fluoro-benzylamide (SHA 68)
Trapella, Claudio,Pela, Michela,Del Zoppo, Luisa,Calo, Girolamo,Camarda, Valeria,Ruzza, Chiara,Cavazzini, Alberto,Costa, Valentina,Bertolasi, Valerio,Reinscheid, Rainer K.,Salvadori, Severo,Guerrini, Remo
experimental part, p. 2738 - 2744 (2011/06/27)
This study reports the synthesis, chromatographic separation, and pharmacological evaluation of the two enantiomers of the neuropeptide S receptor (NPSR) antagonist (9R/S)-3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine- 7-carboxylic acid 4-fluoro-be
Asymmetrie transfer hydrogenation of ketones catalyzed by amino acid derived rhodium complexes: on the origin of enantioselectivity and enantioswitchability
Ahlford, Katrin,Ekstr?m, Jesper,Zaitsev, Alexey B.,Ryberg, Per,Eriksson, Lars,Adolfsson, Hans
supporting information; experimental part, p. 11197 - 11209 (2010/04/26)
Amino acid based thioamides, hydroxamic acids, and hydrazides have been evaluated as ligands in the rhodium-catalyzed asymmetric transfer hydrogenation of ketones in 2propanol. Catalysts containing thioamide ligands derived from L-valine were found to selectively generate the product with an R configuration (95 % ee), whereas the corresponding Lvaline-based hydroxamic acids or hydrazides facilitated the formation of the (S)-alcohols (97 and 91% ee, respectively). The catalytic reduction was examined by performing a structureactivity correlation investigation with differently functionalized or substituted ligands and the results obtained indicate that the major difference between the thioamide and hydroxamic acid based catalysts is the coordination mode of the ligands. Kinetic experiments were performed and the rate constants for the reduction reactions were determined by using rhodiumarene catalysts derived from amino acid thioamide and hydroxamic acid ligands. The data obtained show that the thioamide-based catalyst systems dem-onstrate a pseudo-first-order dependence on the substrate, whereas pseudozero-order dependence was observed for the hydroxamic acid containing catalysts. Furthermore, the kinetic experiments revealed that the rate-limiting steps of the two catalytic systems differ. From the data obtained in the structure-activity correlation investigation and along with the kinetic investigation it was concluded that the enantioswitchable nature of the catalysts studied originates from different ligand coordination, which affects the ratelimiting step of the catalytic reduction reaction.
