171092-38-9Relevant academic research and scientific papers
Core refinement toward permeable β-secretase (BACE-1) inhibitors with low hERG activity
Ginman, Tobias,Viklund, Jenny,Malmstr?m, Jonas,Blid, Jan,Emond, Rikard,Forsblom, Rickard,Johansson, Anh,Kers, Annika,Lake, Fredrik,Sehgelmeble, Fernando,Sterky, Karin J.,Bergh, Margareta,Lindgren, Anders,Johansson, Patrik,Jeppsson, Fredrik,F?lting, Johanna,Gravenfors, Ylva,Rahm, Fredrik
supporting information, p. 4181 - 4205 (2013/07/19)
By use of iterative design aided by predictive models for target affinity, brain permeability, and hERG activity, novel and diverse compounds based on cyclic amidine and guanidine cores were synthesized with the goal of finding BACE-1 inhibitors as a treatment for Alzheimer's disease. Since synthesis feasibility had low priority in the design of the cores, an extensive synthesis effort was needed to make the relevant compounds. Syntheses of these compounds are reported, together with physicochemical properties and structure-activity relationships based on in vitro data. Four crystal structures of diverse amidines binding in the active site are deposited and discussed. Inhibitors of BACE-1 with 3 μM to 32 nM potencies in cells are shown, together with data on in vivo brain exposure levels for four compounds. The results presented show the importance of the core structure for the profile of the final compounds.
Ether-imidazolium carbenes for Suzuki-Miyaura cross-coupling of heteroaryl chlorides with Aryl/heteroarylboron reagents
Kuriyama, Masami,Matsuo, Seira,Shinozawa, Mina,Onomura, Osamu
supporting information, p. 2716 - 2719 (2013/07/19)
Easily accessible and handled ether-imidazolium chlorides were developed as ligand precursors. The coupling reactions of heteroaryl chlorides with aryl/heteroarylboronic acids and esters were catalyzed by the palladium/ether-imidazolium chloride system with high substrate tolerance to give various heterobiaryls in good to excellent yields.
Efficient diphosphane-based catalyst for the palladium-catalyzed suzuki cross-coupling reaction of 3-pyridylboronic acids
Fu, Xing-Li,Wu, Lei-Lei,Fu, Hai-Yan,Chen, Hua,Li, Rui-Xiang
experimental part, p. 2051 - 2054 (2009/09/06)
A highly active catalyst system derived from PdCl2 and 2,2',6,6'- tetramethoxy-4,4'-bis(diphenylphosphanyl)-3,3'-bi- pyridine (P-Phos) has been developed for the Suzuki cross- coupling reaction of pyridylboronic acid with a variety of aryl halides in good to excellent yields, even in the presence of hindered and functional groups. In addition, P-Phos also exhibited high activity in the palladium-catalyzed Suzuki reaction of 2,6-dimethoxypyridylboronic acid in excellent yields with a fast rate. The steric and electronic effects of the P- Phos-palladium complex to this cross-coupling reaction were also discussed.
Kinetic resolution of 1-biaryl- and 1-(pyridylphenyl)alkan-1-ols catalysed by the lipase b from Candida antarctica
Kourist, Robert,Gonzalez-Sabin, Javier,Liz, Ramon,Rebolledo, Francisca
, p. 695 - 702 (2007/10/03)
Lipase B from Candida antarctica (CAL-B) catalyses the highly enantioselective (E > 200) transesterification of some 1-biaryl-2-yl-, -3-yl-, and -4-yl-ethanols and -propan-1-ols, as well as 1-(o-, m-, and p-pyridylphenyl)ethanols, 6, with vinyl acetate, Kazlauskas' rule being obeyed in all cases, meta and para-Substituted substrates were transformed within several hours (conversion degree ranging from 23-50%), reaction rates for propan-1-ol derivatives being slower than those for ethanol derivatives. Transesterifications of ortho-substituted alcohols took several days and were accompanied by a chemoenzymatic side reaction: the formation of another acetate derived from the hemiacetal between 6 and acetaldehyde coming from vinyl acetate. This side reaction was suppressed in the presence of isopropenyl acetate as acyl donor, conversion degrees for transesterification ranging from 20-40% after ten days (E > 200). The usefulness of (R)-6p as ligand in the asymmetric addition of diethylzinc to benzaldehyde was also demonstrated.
Ligands for metals and improved metal-catalyzed processes based thereon
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, (2008/06/13)
One aspect of the present invention relates to ligands for transition metals. A second aspect of the present invention relates to the use of catalysts comprising these ligands in transition metal-catalyzed carbon-heteroatom and carbon-carbon bond-forming reactions. The subject methods provide improvements in many features of the transition metal-catalyzed reactions, including the range of suitable substrates, reaction conditions, and efficiency.
Ligands for metals and improved metal-catalyzed processes based thereon
-
, (2008/06/13)
One aspect of the present invention relates to novel ligands for transition metals. A second aspect of the present invention relates to the use of catalysts comprising these ligands in transition metal-catalyzed carbon-heteroatom and carbon-carbon bond-forming reactions. The subject methods provide improvements in many features of the transition metal-catalyzed reactions, including the range of suitable substrates, reaction conditions, and efficiency.
Highly active palladium catalysts for Suzuki coupling reactions
Wolfe, John P.,Singer, Robert A.,Yang, Bryant H.,Buchwald, Stephen L.
, p. 9550 - 9561 (2007/10/03)
Mixtures of palladium acetate and o-(di-tert-butylphosphino)biphenyl (4) catalyze the room-temperature Suzuki coupling of aryl bromides and aryl chlorides with 0.5-1.0 mol % Pd. Use of o-(dicyclohexylphosphino)biphenyl (2) allows Suzuki couplings to be carried out at low catalyst loadings (0.000001-0.02 mol % Pd). The process tolerates a broad range of functional groups and substrate combinations including the use of sterically hindered substrates. This is the most active catalyst system in terms of reaction temperature, turnover number, and steric tolerance which has been reported to date.
