103-87-7Relevant academic research and scientific papers
The role of β-cyclodextrin in mediating regioselective dimethylaminomethylation of phenol
Wu, Wen-Hai,Duan, Jiang,Wei, Ting,Tu, Hai-Yang,Zhang, Ai-Dong
, p. 360 - 365 (2018)
Regioselective reactions with supramolecular control are of great interest. Herein, the para-regioselectivity in the Mannich reaction of phenol with formaldehyde and dimethylamine was achieved with the use of β-cyclodextrin (β-CD), giving 4-(N,N-dimethylaminomethyl)phenol (p-AP) as major product. 1H NMR and ITC measurements of the binding of β-CD with the reactants and the products o- and p-AP revealed a new mechanism, in which β-CD includes p-AP instead of phenol to control the reaction regioselectivity. This product-inclusion mechanism is remarkably different to the known reactant-inclusion process.
REACTIONS RETRODIENIQUES-XI SYNTHESE DE COMPOSES POLYINSATURES REACTIFS PAR DOUBLE REACTION DE RETRO-DIELS-ALDER
Lasne, M. C.,Ripoll, J. L.,Denis, J. M.
, p. 503 - 508 (1981)
Double retro-Diels-Alder cleavage by flash thermolysis gave the new, unstable polyunsaturated ketones and hydrocarbons 1-5 for which NMR, IR and UV spectra at low temperature are reported.The Diels-Alder adducts of compounds 1-3 with various dienes, the 1,6-additions of several nucleophilic agents with 4, and the isomerisation of 5 in p-ethynylstyrene support the proposed structures.
Simplified preparation of a graphene-co-shelled Ni/NiO@C nano-catalyst and its application in theN-dimethylation synthesis of amines under mild conditions
Liu, Jianguo,Ma, Longlong,Song, Yanpei,Zhang, Mingyue,Zhuang, Xiuzheng
supporting information, p. 4604 - 4617 (2021/06/30)
The development of Earth-abundant, reusable and non-toxic heterogeneous catalysts to be applied in the pharmaceutical industry for bio-active relevant compound synthesis remains an important goal of general chemical research.N-methylated compounds, as one of the most essential bioactive compounds, have been widely used in the fine and bulk chemical industries for the production of high-value chemicals. Herein, an environmentally friendly and simplified method for the preparation of graphene encapsulated Ni/NiO nanoalloy catalysts (Ni/NiO@C) was developed for the first time, for the highly selective synthesis ofN-methylated compounds using various functional amines and aldehydes under easy to handle, and industrially applicable conditions. A large number of primary and secondary amines (more than 70 examples) could be converted to the correspondingN,N-dimethylamines with the participation of different functional aldehydes, with an average yield of over 95%. A gram-scale synthesis also demonstrated a similar yield when compared with the benchmark test. In addition, it was further proved that the catalyst could easily be recycled because of its intrinsic magnetism and reused up to 10 times without losing its activity and selectivity. Also, for the first time, the tandem synthesis ofN,N-dimethylamine products in a one-pot process, using only a single earth-abundant metal catalyst, whose activity and selectivity were more than 99% and 94%, respectively, for all tested substrates, was developed. Overall, the advantages of this newly developed method include operational simplicity, high stability, easy recyclability, cost-effectiveness of the catalyst, and good functional group compatibility for the synthesis ofN-methylation products as well as the industrially applicable tandem synthesis process.
Discovery of (3-(4-(2-Oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone (AZD1979), a Melanin Concentrating Hormone Receptor 1 (MCHr1) Antagonist with Favorable Physicochemical Properties
Johansson, Anders,L?fberg, Christian,Antonsson, Madeleine,Von Unge, Sverker,Hayes, Martin A.,Judkins, Robert,Ploj, Karolina,Benthem, Lambertus,Lindén, Daniel,Brodin, Peter,Wennerberg, Marie,Fredenwall, Marléne,Li, Lanna,Persson, Joachim,Bergman, Rolf,Pettersen, Anna,Gennemark, Peter,Hogner, Anders
, p. 2497 - 2511 (2016/04/10)
A novel series of melanin concentrating hormone receptor 1 (MCHr1) antagonists were the starting point for a drug discovery program that culminated in the discovery of 103 (AZD1979). The lead optimization program was conducted with a focus on reducing lipophilicity and understanding the physicochemical properties governing CNS exposure and undesired off-target pharmacology such as hERG interactions. An integrated approach was taken where the key assay was ex vivo receptor occupancy in mice. The candidate compound 103 displayed appropriate lipophilicity for a CNS indication and showed excellent permeability with no efflux. Preclinical GLP toxicology and safety pharmacology studies were without major findings and 103 was taken into clinical trials.
Phenyl ether- and aniline-containing 2-aminoquinolines as potent and selective inhibitors of neuronal nitric oxide synthase
Cinelli, Maris A.,Li, Huiying,Pensa, Anthony V.,Kang, Soosung,Roman, Linda J.,Martásek, Pavel,Poulos, Thomas L.,Silverman, Richard B.
supporting information, p. 8694 - 8712 (2015/11/25)
Excess nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is implicated in neurodegenerative disorders. As a result, inhibition of nNOS and reduction of NO levels is desirable therapeutically, but many nNOS inhibitors are poorly bioavailable. Promising members of our previously reported 2-aminoquinoline class of nNOS inhibitors, although orally bioavailable and brain-penetrant, suffer from unfavorable off-target binding to other CNS receptors, and they resemble known promiscuous binders. Rearranged phenyl ether- and aniline-linked 2-aminoquinoline derivatives were therefore designed to (a) disrupt the promiscuous binding pharmacophore and diminish off-target interactions and (b) preserve potency, isoform selectivity, and cell permeability. A series of these compounds was synthesized and tested against purified nNOS, endothelial NOS (eNOS), and inducible NOS (iNOS) enzymes. One compound, 20, displayed high potency, selectivity, and good human nNOS inhibition, and retained some permeability in a Caco-2 assay. Most promisingly, CNS receptor counterscreening revealed that this rearranged scaffold significantly reduces off-target binding.
APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES
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Page/Page column 111, (2010/07/04)
Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein.
Aplysamine-1 and related analogs as histamine H3 receptor antagonists
Swanson, Devin M.,Wilson, Sandy J.,Boggs, Jamin D.,Xiao, Wei,Apodaca, Richard,Barbier, Ann J.,Lovenberg, Timothy W.,Carruthers, Nicholas I.
, p. 897 - 900 (2007/10/03)
Aplysamine-1 (1), a marine natural product, was synthesized and screened for in vitro activity at the human and rat histamine H3 receptors. Aplysamine-1 (1) was found to possess a high binding affinity for the human H3 receptor (Ki = 30 ± 4 nM). Synthetic analogs of 1, including des-bromoaplysamine-1 (10) and dimethyl-{2-[4-(3-piperidin-1-yl- propoxy)-phenyl]-ethyl}-amine (13), were potent H3 antagonists.
Design of ionic phosphites for catalytic hydrocyanation reaction of 3-pentenenitrile in ionic liquids
Vallee, Christophe,Chauvin, Yves,Basset, Jean-Marie,Santini, Catherine C.,Galland, Jean-Christophe
, p. 1835 - 1847 (2007/10/03)
The synthesis and characterization of a novel class of ionic phosphites bearing either a single cationic group obtained by quaternization of aminophosphites or three cationic groups prepared by reaction of phosphorus trichloride with imidazolium phenols are reported. The catalytic hydrocyanation reaction of 3-pentenenitrile (3PN) into adiponitrile has been performed in the presence of Ni(0) with ionic phosphite ligands, and a Lewis acid in biphasic ionic liquid/organic solvent system. The screening of several original cationic phosphites was performed and the experimental conditions were optimized for the tricationic phosphite tris-4-[(2,3-dimethylimidazol-1-yl) methyl]phenyl phosphite tris[bis(trifluoromethylsulfonyl)amide]. It is possible to obtain performance similar to molecular systems and the catalyst and the Lewis acid were immobilized in the ionic phase.
Design, synthesis, and evaluation of 2-phenoxy-indan-1-one derivatives as acetylcholinesterase inhibitors
Sheng, Rong,Lin, Xiao,Li, Jingya,Jiang, Yanke,Shang, Zhicai,Hu, Yongzhou
, p. 3834 - 3837 (2007/10/03)
A series of 2-phenoxy-indan-1-one derivatives have been designed, synthesized, and tested as acetylcholinesterase inhibitors. The most potent compound exhibited high AChE inhibitory activity (IC50 = 50 nM), and the molecular docking study indicated that it was nicely accommodated by AChE.
MANNICH REACTIONS OF ARYLTRIALKYLSTANNANES IN APROTIC SOLVENTS
Cooper, Mark S.,Fairhurst, Robin A.,Heaney, Harry,Papageorgiou, George,Wilkins, Robert F.
, p. 1155 - 1166 (2007/10/02)
Aryltributyl- and aryltrimethyl-stannanes react with a range of N,N-dialkylmethylene-imonium salts to afford N,N-dialkylaminomethyl derivatives in good yields.The method can be used to obtain regioisomers that are not available using classical procedures. "In situ" reactions can also be carried out using alkoxydialkylaminomethanes (aminol ethers) and bis(dialkylamino)methanes (aminals) together with chlorotrimethyl- and trichloromethyl-silanes as the source of the electrophile.However, the "in situ" reactions do not afford good yields in the majority of cases, as a result of the inhibition of imonium salt formation by trialkylchlorostannane.
