26077-80-5Relevant articles and documents
A reversible and selective inhibitor of monoacylglycerol lipase ameliorates multiple sclerosis
Hernndez-Torres, Gloria,Cipriano, Mariateresa,Hedn, Erika,Bj?rklund, Emmelie,Canales, Angeles,Zian, Debora,Feli, Ana,Mecha, Miriam,Guaza, Carmen,Fowler, Christopher J.,Ortega-Gutirrez, Silvia,Lpez-Rodrguez, Maria L.
, p. 13765 - 13770 (2015/01/16)
Monoacylglycerol lipase (MAGL) is the enzyme responsible for the inactivation of the endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL inhibitors show analgesic and tissue-protecting effects in several disease models. However, the few efficient and selective MAGL inhibitors described to date block the enzyme irreversibly, and this can lead to pharmacological tolerance. Hence, additional classes of MAGL inhibitors are needed to validate this enzyme as a therapeutic target. Here we report a potent, selective, and reversible MAGL inhibitor (IC50 = 0.18 mm) which is active in vivo and ameliorates the clinical progression of a multiple sclerosis (MS) mouse model without inducing undesirable CB1-mediated side effects. These results support the interest in MAGL as a target for the treatment of MS.
Structure-activity relationship of a new series of reversible dual monoacylglycerol lipase/fatty acid amide hydrolase 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.
, p. 824 - 836 (2012/04/10)
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.
Photochemistry of benzophenone immobilized in a major groove of DNA: Formation of thermally reversible interstrand cross-link
Nakatani, Kazuhiko,Yoshida, Takashi,Saito, Isao
, p. 2118 - 2119 (2007/10/03)
We here report a highly site and sequence selective formation of an interstrand cross-link of BPU-containing oligomer duplexes. The cross-link was found spontaneously reverted to original oligomers upon heating, providing a new method for the temporary connection of two DNA strands. Copyright
Electro-organic reactions. Part 54: Quinodimethane chemistry; Part 2 - Electrogeneration and reactivity of o-quinodimethanes
Utley, James H.P.,Ramesh, Shalini,Salvatella, Xavier,Szunerits, Sabine,Motevalli, Majid,Nielsen, Merete F.
, p. 153 - 163 (2007/10/03)
The electrochemical generation and characterisation of a variety of o-quinodimethanes (o-QDMs) are described together with the outcome of preparative experiments in which they are key intermediates. The quinodimethanes are conveniently formed, in DMF, by both direct and redox-catalysed electroreduction of 1,2-bis(halomethyl)arenes. Their predominant reaction is polymerisation to poly(o-xylylene) (o-PX) polymers. In the presence of dienophiles the electrogenerated o-QDMs may undergo efficient cycloaddition reaction and distinctions between the possible mechanisms have been attempted on the basis of voltammetric, preparative and stereochemical experiments. Contrary to the precedent of the corresponding methyl ester, diphenyl maleate radical-anion isomerises only slowly to the fumarate radical-anion, yet co-electrolysis of 2,3-bis(bromomethyl)-1,4-dimethoxybenzene and diphenyl maleate or diphenyl fumarate gives exclusively the corresponding trans-adduct. Co-electrolysis of dimethyl maleate with either 1,2-bis(bromomethyl)benzene (more easily reduced) or 2,3-bis(bromomethyl)-1,4-dimethoxybenzene (less easily reduced) gave only o-PX polymer. The results are rationalised in terms of a double nucleophilic substitution mechanism where electron transfer between dienophile radical-anion and dihalide is relatively slow. Where electron transfer from maleate or fumarate radical-anions is likely to be fast o-quinodimethanes are formed by redox-catalysis and they polymerise rather than undergo Diels-Alder reaction. Dimerisation of the dienophile radical-anions, with k2 = 104 to 105 M-1 s-1, does not apparently compete with nucleophilic substitution or, where relevant, electron transfer.
Efficient photodecarboxylation of aroyl-substituted phenylacetic acids in aqueous solution: A general photochemical reaction
Xu,Wan
, p. 2147 - 2148 (2007/10/03)
Photolysis (254-350 nm) of a variety of aroyl-substituted phenylacetic acids and p-acetylphenylacetic acid in aqueous solution at pH > pK(a) resulted in efficient photodecarboxylation (Φ = 0.2-0.7), to give in most cases a single product arising via the corresponding arylmethyl carbanion, indicating that photodecarboxylation is an efficient and general reaction for these types of compounds.
p-cyano substituted benzophenone as an excellent photophore for one- electron oxidation of DNA
Nakatani, Kazuhiko,Dohno, Chikara,Nakamura, Takashi,Saito, Isao
, p. 2779 - 2782 (2007/10/03)
Novel DNA-photocleaving molecule 1 consisting of a p-cyano substituted benzophenone photophore and an alkyl amino side chain was developed. DNA cleavage by 1 under photoirradiation conditions occurred selectively at 5' side G of 5'GG3' sequence after hot
Liquid Crystalline Properties of Cholesteryl ω-Arylalkanoates
Koden, Mitsuhiro,Miyake, Shiro,Takenaka, Shunsuke,Kusabayashi, Shigekazu
, p. 2387 - 2390 (2007/10/02)
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.
Benzoylphenylacetic acid derivatives with antiinflammatory and analgesic activities
Allais,Rousseau,Meier,et al.
, p. 381 - 389 (2007/10/06)
Several derivatives of m benzoylphenylacetic acid showed interesting antiinflammatory and analgesic properties associated with good gastric tolerance.
