- Structure-activity relationship of a new series of reversible dual monoacylglycerol lipase/fatty acid amide hydrolase inhibitors
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The two endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), play independent and nonredundant roles in the body. This makes the development of both selective and dual inhibitors of their inactivation an important priority. In this work we report a new series of inhibitors of monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH). Among them, (±)-oxiran-2-ylmethyl 6-(1,1′-biphenyl-4-yl)hexanoate (8) and (2R)-(-)-oxiran-2-ylmethyl(4-benzylphenyl)acetate (30) stand out as potent inhibitors of human recombinant MAGL (IC50 (8) = 4.1 μM; IC 50 (30) = 2.4 μM), rat brain monoacylglycerol hydrolysis (IC 50 (8) = 1.8 μM; IC50 (30) = 0.68 μM), and rat brain FAAH (IC50 (8) = 5.1 μM; IC50 (30) = 0.29 μM). Importantly, and in contrast to the other previously described MAGL inhibitors, these compounds behave as reversible inhibitors either of competitive (8) or noncompetitive nature (30). Hence, they could be useful to explore the therapeutic potential of reversible MAGL inhibitors.
- Cisneros, José A.,Bj?rklund, Emmelie,González-Gil, Inés,Hu, Yanling,Canales, ángeles,Medrano, Francisco J.,Romero, Antonio,Ortega-Gutiérrez, Silvia,Fowler, Christopher J.,López-Rodríguez, María L.
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supporting information; experimental part
p. 824 - 836
(2012/04/10)
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- Novel Rh catalysis in cross-coupling between alkyl halides and arylzinc compounds possessing ortho-COX (X = OR, NMe2, or Ph) groups
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Rh-dppf was found to be an efficient catalyst for the cross-coupling between primary alkyl halides bearings-hydrogens and arylzinc compounds possessing carbonyl groups such as ester, amide, or ketone at the ortho position. Various functional groups such as ester, nitrite, or acyloxylate moieties on the halides were tolerated under the catalysis conditions. Arylzinc compounds free of ortho-carbonyl groups reacted well with ethyl 3-iodopropanoate, suggesting that the essential intramolecular interaction between carbonyl groups and Rh promotes the reductive elimination.
- Takahashi, Hideki,Inagaki, Shinya,Nishihara, Yasushi,Shibata, Takanori,Takagi, Kentaro
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p. 3037 - 3040
(2007/10/03)
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- Synthesis of photoaffinity derivatives of adenophostin A
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Photoaffinity derivatives 7 and 8 of adenophostin A, modified at the 5'- and 1'-positions, were prepared by a chemoselective reaction of the aminophostins 15 and 30 with N-succini-midyl p-benzoyl-2,3-dihydrocinnamate (p-benzoyldihydrocinnamoyl-N-hydroxysu
- De Kort, Martin,Luijendijk, Jaco,Van Der Marel, Gijs A.,Van Boom, Jacques H.
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p. 3085 - 3092
(2007/10/03)
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- Synthesis and thoromboxane A2 antagonistic activity of [[1-aryl(or benzyl)-1-(benzenesulfonamido)methyl]phenyl]alkanoic acid derivatives
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In order to find a new antiasthmatic and antithrombotic agents, various [[1-aryl(or benzyl)-1-(benzenesulfonamido)methyl]phenyl]alkanoic acid derivatives were synthesized. Evaluation of these compounds for thromboxane A2 (TXA2) antag
- Sakurai,Ogawa,Suzuki,Kato,Ohashi,Yasuda,Kato,Ito
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p. 765 - 777
(2007/10/03)
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- Liquid Crystalline Properties of Cholesteryl ω-Arylalkanoates
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The thermal properties of the homologous series of cholesteryl ω-(4-benzoylphenyl)- (I), ω-(4-benzylphenyl)- (II), ω-benzoyl- (III), and ω-phenoxyalkanoate (IV) have been investigated.For series I and II the cholesteric-isotropic (Ch-I) transition temperatures, enthalpies, and entropies show a remarkable alternation.For series III and IV, the transition temperatures, enthalpies, and entropies exhibit weak alternation and their trends are opposite to those for series I and II, and the cholesteryl ω-phenylalkanoates.The cholesteric-isotropic transition temperatures are discussed in terms of the geometrical and electrical alternations stemming from the terminal aryl groups, and also the relative importance between these two terms.
- Koden, Mitsuhiro,Miyake, Shiro,Takenaka, Shunsuke,Kusabayashi, Shigekazu
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p. 2387 - 2390
(2007/10/02)
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- Benzalicyclic carboxylic acid derivative
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Compounds of the formula: SPC1 Wherein R1 is an aryl group which may be substituted, R2 is hydrogen or a lower alkyl group having 1 to 4 carbon atoms and n is 1 or 2, or derivatives at the carboxyl function thereof, are useful as medicines such as antipyretics, analgesics and anti-inflammatory agents.
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