24197-95-3Relevant articles and documents
Mustard Carbonate Analogues as Sustainable Reagents for the Aminoalkylation of Phenols
Annatelli, Mattia,Trapasso, Giacomo,Salaris, Claudio,Salata, Cristiano,Castellano, Sabrina,Aricò, Fabio
supporting information, p. 3459 - 3464 (2021/05/24)
N,N-dialkyl ethylamine moiety can be found in numerous scaffolds of macromolecules, catalysts, and especially pharmaceuticals. Common synthetic procedures for its incorporation in a substrate relies on the use of a nitrogen mustard gas or on multistep syntheses featuring chlorine hazardous/toxic chemistry. Reported herein is a one-pot synthetic approach for the easy introduction of aminoalkyl chain into different phenolic substrates through dialkyl carbonate (β-aminocarbonate) chemistry. This new direct alcohol substitution avoids the use of chlorine chemistry, and it is efficient on numerous pharmacophore scaffolds with good to quantitative yield. The cytotoxicity via MTT of the β-aminocarbonate, key intermediate of this synthetic approach, was also evaluated and compared with its alcohol precursor.
Acridone-based inhibitors of inosine 5′-monophosphate dehydrogenase: Discovery and SAR leading to the identification of N-(2-(6-(4-ethylpiperazin-1- yl)pyridin-3-yl)propan-2-yl)-2-fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide (BMS-566419)
Watterson, Scott H.,Chen, Ping,Zhao, Yufen,Gu, Henry H.,Dhar, T. G. Murali,Xiao, Zili,Ballentine, Shelley K.,Shen, Zhongqi,Fleener, Catherine A.,Rouleau, Katherine A.,Obermeier, Mary,Yang, Zheng,McIntyre, Kim W.,Shuster, David J.,Witmer, Mark,Dambach, Donna,Chao, Sam,Mathur, Arvind,Chen, Bang-Chi,Barrish, Joel C.,Robl, Jeffrey A.,Townsend, Robert,Iwanowicz, Edwin J.
, p. 3730 - 3742 (2008/02/12)
Inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosine nucleotides, catalyzes the irreversible nicotinamide-adenine dinucleotide dependent oxidation of inosine-5′- monophosphate to xanthosine-5′-monophosphate. Mycophenolate Mofetil (MMF), a prodrug of mycophenolic acid, has clinical utility for the treatment of transplant rejection based on its inhibition of IMPDH. The overall clinical benefit of MMF is limited by what is generally believed to be compound-based, dose-limiting gastrointestinal (GI) toxicity that is related to its specific pharmacokinetic characteristics. Thus, development of an IMPDH inhibitor with a novel structure and a different pharmacokinetic profile may reduce the likelihood of GI toxicity and allow for increased efficacy. This article will detail the discovery and SAR leading to a novel and potent acridone-based IMPDH inhibitor 4m and its efficacy and GI tolerability when administered orally in a rat adjuvant arthritis model.
METHOD FOR PRODUCING AMINOALKOXY BENZYLAMINES AND AMINOALKOXY BENZONITRILES AS INTERMEDIATES
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Page/Page column 8-9, (2010/11/30)
The invention relates to methods for producing 4-[aminoalkoxy]benzylamines of general formula (I) by means of catalytic hydrogenation of 4-[aminoalkoxy]benzonitriles of general formula (II). In the compounds of general formulae (I) and (II), R1 represents C1-C8 alkylene, and R2 and R3 independently represent C1-C8 alkyl or are linked to form a ring which can also contain a heteroatom. The hydrogenation is carried out at increased pressure and increased temperatures. The invention also relates to a method for producing the intermediate (II).
