300821-91-4Relevant articles and documents
Development and Pharmacological Characterization of Selective Blockers of 2-Arachidonoyl Glycerol Degradation with Efficacy in Rodent Models of Multiple Sclerosis and Pain
Brindisi, Margherita,Maramai, Samuele,Gemma, Sandra,Brogi, Simone,Grillo, Alessandro,Di Cesare Mannelli, Lorenzo,Gabellieri, Emanuele,Lamponi, Stefania,Saponara, Simona,Gorelli, Beatrice,Tedesco, Daniele,Bonfiglio, Tommaso,Landry, Christophe,Jung, Kwang-Mook,Armirotti, Andrea,Luongo, Livio,Ligresti, Alessia,Piscitelli, Fabiana,Bertucci, Carlo,Dehouck, Marie-Pierre,Campiani, Giuseppe,Maione, Sabatino,Ghelardini, Carla,Pittaluga, Anna,Piomelli, Daniele,Di Marzo, Vincenzo,Butini, Stefania
, p. 2612 - 2632 (2016/04/10)
We report the discovery of compound 4a, a potent β-lactam-based monoacylglycerol lipase (MGL) inhibitor characterized by an irreversible and stereoselective mechanism of action, high membrane permeability, high brain penetration evaluated using a human in vitro blood-brain barrier model, high selectivity in binding and affinity-based proteomic profiling assays, and low in vitro toxicity. Mode-of-action studies demonstrate that 4a, by blocking MGL, increases 2-arachidonoylglycerol and behaves as a cannabinoid (CB1/CB2) receptor indirect agonist. Administration of 4a in mice suffering from experimental autoimmune encephalitis ameliorates the severity of the clinical symptoms in a CB1/CB2-dependent manner. Moreover, 4a produced analgesic effects in a rodent model of acute inflammatory pain, which was antagonized by CB1 and CB2 receptor antagonists/inverse agonists. 4a also relieves the neuropathic hypersensitivity induced by oxaliplatin. Given these evidence, 4a, as MGL selective inhibitor, could represent a valuable lead for the future development of therapeutic options for multiple sclerosis and chronic pain.
Amines vs. N-Oxides as Organocatalysts for Acylation, Sulfonylation and Silylation of Alcohols: 1-Methylimidazole N-Oxide as an Efficient Catalyst for Silylation of Tertiary Alcohols
Murray, James I.,Spivey, Alan C.
supporting information, p. 3825 - 3830 (2016/01/25)
A comparison of the relative catalytic efficiencies of Lewis-basic amines vs. N-oxides for the acylation, sulfonylation and silylation of primary, secondary and tertiary alcohols is reported. Whilst the amines are generally superior to the N-oxides for acylation, the N-oxides are superior for sulfonylation and silylation. In particular, 1-methylimidazole N-oxide (NMI-O) is found to be a highly efficient catalyst for sulfonylation and silylation reactions. To the best of our knowledge, NMI-O is the first amine or N-oxide Lewis basic organocatalyst capable of promoting the efficient silylation of tert-alcohols in high yield with low catalyst loading under mild reaction conditions.
Structure-activity relationship of dihydroimidazo-, dihydropyrimido, tetrahydrodiazepino-[2,1-b]-thiazoles, and -benzothiazoles as an acylation catalyst
Okamoto, Sentaro,Sakai, Yuzo,Watanabe, Saki,Nishi, Shohei,Yoneyama, Aya,Katsumata, Hitomi,Kosaki, Yu,Sato, Rumi,Shiratori, Megumi,Shibuno, Misuzu,Shishido, Tsukasa
, p. 1909 - 1912 (2014/03/21)
Cyclic isothioureas 1, 2, 3, and 4 were synthesized through a four-step procedure from the corresponding ortho-bromoanilines 10 via Pd- or Cu-catalyzed cyclization-benzothiazole formation. Nonbenzo analogues 7, 8, and 9 were synthesized by a condensation reaction of cyclic thioureas 15 and α-bromoacetophenones 14. Investigations of the acylation reactions of 1-phenylethanol with acid anhydrides in the presence of these cyclic isothiourea catalysts revealed their structure-activity relationships. Remarkable electronic effects resulting from substituent(s) on a benzo or phenyl moiety and the influence of the size of the annulating ring were observed. Introduction of an electron-donating substituent(s) enhanced the reaction rate. A few substitution effects on chiral catalysts of type 3 and 7 were also studied.
Isothiourea-mediated stereoselective C-acylation of silyl ketene acetals
Woods, Philip A.,Morrill, Louis C.,Lebl, Tomas,Slawin, Alexandra M. Z.,Bragg, Ryan A.,Smith, Andrew D.
supporting information; experimental part, p. 2660 - 2663 (2010/08/21)
Isothiourea DHPB promotes the diastereoselective C-acylation of silyl ketene acetals with anhydrides or benzoyl fluoride, giving 3-acyl-3-aryl or 3-acyl-3-alkylfuranones in excellent yields and stereoselectivities (up to 99:1 dr).
Amidine catalysed O- to C-carboxyl transfer of heterocyclic carbonate derivatives
Joannesse, Caroline,Simal, Carmen,Concellon, Carmen,Thomson, Jennifer E.,Campbell, Craig D.,Slawin, Alexandra M. Z.,Smith, Andrew D.
experimental part, p. 2900 - 2907 (2009/02/02)
The structural requirements of amidines necessary to act as efficient O- to C-carboxyl transfer agents are delineated and the scope of this process outlined through its application to a range of oxazolyl, benzofuranyl and indolyl carbonates. The Royal Society of Chemistry.
Nonaromatic amidine derivatives as acylation catalysts
Birman, Vladimir B.,Li, Ximin,Han, Zhenfu
, p. 37 - 40 (2007/10/03)
(Chemical Equation Presented) Catalytic activity of nonaromatic bicyclic amidines and bicyclic isothioureas in acylation reactions was found to be remarkably dependent on the sizes of both rings. DBN and especially its thia-analogue (THTP) have been identified as highly active acylation catalysts.
Unexpected reactivity of annulated 3H-benzothiazol-2-ylideneamines as an acyl transfer catalyst
Kobayashi, Megumi,Okamoto, Sentaro
, p. 4347 - 4350 (2007/10/03)
Catalytic ability of annulated 3H-benzothiazol-2-ylideneamines and 1H-pyridin-2-ylideneamines for acylation of alcohols was investigated and 3,4-dihydro-2H-9-thia-1,4a-diazafluorene (2b) was found to be an extremely effective catalyst, the reaction with which was faster than that with DMAP.
