40796-00-7Relevant articles and documents
An Electrochemically Promoted, Nickel-Catalyzed Mizoroki-Heck Reaction
Walker, Benjamin R.,Sevov, Christo S.
, p. 7197 - 7203 (2019/08/26)
Despite significant efforts to replace Pd-based catalysts with those of Ni, the Ni-catalyzed Mizoroki-Heck coupling of aryl halides and alkenes remains challenging. This work details the development of a Mizoroki-Heck reaction of aryl halides and a broad range of alkenes that utilizes electrochemistry as a means to promote Ni-catalyzed coupling under mild conditions. Stoichiometric studies implicate low-valent Ni complexes as key intermediates in route to rapid reactions with even unactivated alkenes. As such, electrochemistry is employed to readily provide the reducing potentials necessary to access these reactive intermediates and render the transformation catalytic. Cyclohexenone was found to be an unreactive substrate but a crucial additive that promotes facile electroreduction of the Ni catalyst and functionalization of other alkenes in high yields. Finally, preliminary mechanistic studies suggest that reactions proceed via an electron-chain transfer process that rapidly terminates but is reinitiated upon electroreduction.
Novel Fused Arylpyrimidinone Based Allosteric Modulators of the M1 Muscarinic Acetylcholine Receptor
Mistry, Shailesh N.,Lim, Herman,J?rg, Manuela,Capuano, Ben,Christopoulos, Arthur,Lane, J. Robert,Scammells, Peter J.
, p. 647 - 661 (2016/06/01)
Benzoquinazolinone 1 is a positive allosteric modulator (PAM) of the M1 muscarinic acetylcholine receptor (mAChR), which is significantly more potent than the prototypical PAM, 1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (BQCA). In this study, we explored the structural determinants that underlie the activity of 1 as a PAM of the M1 mAChR. We paid particular attention to the importance of the tricyclic scaffold of compound 1, for the activity of the molecule. Complete deletion of the peripheral fused benzene ring caused a significant decrease in affinity and binding cooperativity with acetylcholine (ACh). This loss of affinity was rescued with the addition of either one or two methyl groups in the 7- and/or 8-position of the quinazolin-4(3H)-one core. These results demonstrate that the tricyclic benzo[h]quinazolin-4(3H)-one core could be replaced with a quinazolin-4(3H)-one core and maintain functional affinity. As such, the quinazolin-4(3H)-one core represents a novel scaffold to further explore M1 mAChR PAMs with improved physicochemical properties.
TETRACYCLIC INHIBITORS OF FATTY ACID AMIDE HYDROLASE
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Page/Page column 37-38, (2009/01/20)
Certain tetracyclic compounds are described, which may be used in pharmaceutical compositions and methods for treating disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity. Thus, the compounds may be administered to treat, e.g., anxiety, pain, inflammation, sleep disorders, eating disorders, or movement disorders (such as multiple sclerosis).
