159153-39-6Relevant articles and documents
Design, synthesis, and characterization of α-ketoheterocycles that additionally target the cytosolic port Cys269 of fatty acid amide hydrolase
Otrubova, Katerina,Cravatt, Benjamin F.,Boger, Dale L.
, p. 1079 - 1089 (2014/03/21)
A series of α-ketooxazoles incorporating electrophiles at the C5 position of the pyridyl ring of 2 (OL-135) and related compounds were prepared and examined as inhibitors of fatty acid amide hydrolase (FAAH) that additionally target the cytosolic port Cys269. From this series, a subset of the candidate inhibitors exhibited time-dependent FAAH inhibition and noncompetitive irreversible inactivation of the enzyme, consistent with the targeted Cys269 covalent alkylation or addition, and maintained or enhanced the intrinsic selectivity for FAAH versus other serine hydrolases. A preliminary in vivo assessment demonstrates that these inhibitors raise endogenous brain levels of anandamide and other FAAH substrates upon intraperitoneal (i.p.) administration to mice, with peak levels achieved within 1.5-3 h, and that the elevations of the signaling lipids were maintained >6 h, indicating that the inhibitors effectively reach and remain active in the brain, inhibiting FAAH for a sustained period.
Dimethyl sulfoxide mediated elimination reactions in 3-aryl 2,3-dihalopropanoates: Scope and mechanistic insights
Li, Wei,Li, Jianchang,Lin, Melissa,Wacharasindhu, Sumrit,Tabei, Keiko,Mansour, Tarek S.
, p. 6016 - 6021 (2008/02/10)
(Chemical Equation Presented) Dimethyl sulfoxide (DMSO) efficiently causes the reductive elimination of 3-aryl 2,3-dibromopropanoates to cinnamates with good yield. With 3-phenyl 2,3-dihalopropanoates, debromination is the major pathway providing 3-phenylacrylate derivatives in high yields, whereas dehydrobromination is a competing pathway with thiophene derivatives. 1H NMR, 81Br NMR, and MS techniques indicated the formation of brominated-DMSO, MeBr, and HBr as byproducts in this transformation with no evidence for the formation of Br2. The dual role of DMSO as a nucleophile and bromine scavenger accounts for the products formed in this reaction.
Ruthenium-Catalyzed Heck-Type Olefination and Suzuki Coupling Reactions: Studies on the Nature of Catalytic Species
Na, Youngim,Park, Soyoung,Han, Soo Bong,Han, Hoon,Ko, Sangwon,Chang, Sukbok
, p. 250 - 258 (2007/10/03)
Ruthenium-catalyzed Heck olefination and Suzuki cross coupling reactions have been developed. When starting with a ruthenium complex [RuCl 2(p-cymene)]2 as a homogeneous catalyst precursor, induction periods were observed and ruthenium colloids of zero oxidation state were generated under catalytic conditions. Isolated ruthenium colloids carried out the olefination, implying that active catalytic species are ruthenium nanoclusters. To support this hypothesis, ruthenium nanoparticles stabilized with dodecylamine were independently prepared via a hydride reduction procedure, and their catalytic activity was subsequently examined. Olefination of iodobenzene with ethyl acrylate was efficiently catalyzed by the ruthenium nanoparticles under the same conditions, which could be also reused for the next runs. In poisoning experiments, the conversion of the olefination was completely inhibited in the presence of mercury, thus supporting our assumption on the nature of catalytic species. No residual ruthenium was detected from the filtrate at the end of the reaction. On the basis of the postulation, a heterogeneous catalyst system of ruthenium supported on alumina was consequently developed for the Heck olefination and Suzuki cross coupling reactions for the first time. It turned out that substrate scope and selectivity were significantly improved with the external ligand-free catalyst even under milder reaction conditions when compared to results with the homogeneous precatalyst. It was also observed that the immobilized ruthenium catalyst was recovered and reused up to several runs with consistent efficiency. Especially in the Suzuki couplings, the reactions could be efficiently carried out with as low as 1 molpercent of the supported catalyst over a wide range of substrates and were scaled up to a few grams without any practical problems, giving coupled products with high purity by a simple workup procedure.
