73608-65-8Relevant articles and documents
Simple and efficient one-pot solvent-free synthesis of N-methyl imines of aromatic aldehydes
Radulovi?, Niko S.,Miltojevi?, Ana B.,Vuki?evi?, Rastko D.
, p. 257 - 270 (2013/05/09)
A one-pot solvent-free synthesis of N-methyl imines in good to excellent yields was performed by grinding together aromatic aldehydes and methylamine hydrochloride in the presence of a base. The best yields were achieved when an excess of methylamine hydrochloride and inexpensive sodium hydrogen carbonate was used (usually in a molar ratio ArCHO/CH3NH2· HCl/NaHCO3 = 1:5:5), allowing the reaction to proceed for 1 h (in the case of aromatic aldehydes containing electron-withdrawing substituents) or overnight (in the case of electron-rich aldehydes). After a simple work-up (extraction with diethyl ether) the obtained products were mostly pure enough for spectral characterization. In this way, 31 N-methyl imines were prepared, among which eight were synthesized for the first time. Their structures were elucidated by spectral means (1H- and 13C-NMR, IR, MS) whenever it was possible. In the case of salicylaldehyde and 4-chlorobenzaldehyde, the synthesis of the corresponding imines was also conducted on a gram-scale with a 72% and 84% isolated yield, respectively. The present approach not only provides good to high yields, but also eliminates the disadvantages of the traditional synthesis of N-methyl imines, such as the use of hazardous solvents and more or less expensive catalysts and the necessity of work/handling with an anhydrous gas in pressurized containers.
Indenoisoquinolines as antineoplastic agents
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, (2008/06/13)
A number of indenoisoquinolines were prepared and evaluated for cytotoxicity in human cancer cell cultures and for activity versus topoisomerase I. The two most cytotoxic indenoisoquinolines proved to be cis-6-ethyl-5,6,12,13-tetrahydro-2,3-dimethoxy-8,9(
Synthesis of cytotoxic indenoisoquinoline topoisomerase I poisons
Strumberg, Dirk,Pommier, Yves,Paull, Kenneth,Jayaraman, Muthusamy,Nagafuji, Pamela,Cushman, Mark
, p. 446 - 457 (2007/10/03)
A number of indenoisoquinolines were prepared and evaluated for cytotoxicity in human cancer cell cultures and for activity vs topoisomerase 1 (top1). The two most cytotoxic indenoisoquinolines proved to be cis-6- ethyl-5,6,12,13-tetrahydro-2,3-dimethoxy-8,9-(methylenedioxy)-5,11-dioxo- 11H-indeno[1,2-c]isoquinoline (21) and cis-6-allyl-5,6,12,13-tetrahydro-2,3- dimethoxy-8,9-(methylenedioxy)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (22), both of which displayed submicromolar mean graph midpoints when tested in 55 human cancer cell cultures. Two of the most potent top i inhibitors were 6- (3-carboxy-1-propyl)-5,6-dihydro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (26) and 6-ethyl-2,3-dimethoxy-8,9-(methylenedioxy)-11H-indeno[1,2- c]isoquinolinium Chloride (27), both of which also inhibited top2, unwound DNA, and are assumed to be DNA intercalators. However, two additional potent top1 inhibitors, 6-allyl-5,6-dihydro-2,3-dimethoxy-8,9-(methylenedioxy)- 5,11-dioxo-11H-indeno[1,2-c]isoquinoline (13c) and 5,6-dihydro-6-(4- hydroxybut-1-yl)-2-3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2- c]isoquinoline (19a), did not unwind DNA and did not affect top2. Some of the DNA cleavage sites detected in the presence of the indenoisoquinolines were different from those seen with the camptothecins. The cleavage sites induced by the indenoisoquinolines were reversed by salt treatment, which is consistent with the reversible trapping of top1 clearable complexes by the indenoisoquinolines. In general, the potencies of the indenoisoquinolines as top1 inhibitors did not correlate with their potencies as cytotoxic agents, as some of the most cytotoxic agents had little if any effect on top1. On the other hand, the most potent of the indenoisoquinolines vs top1 were not the most cytotoxic. In several cases, moderate activity was observed for both cytotoxicity and activity vs top1.
