- METHOD FOR PREPARING N-[4-(2-{[2-(4-METHANE SULFONAMIDOPHENOXY) ETHYL](METHYL)AMINO}ETHYL)PHENYL]METHANESULFONAMIDE (DOFETILIDE)
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A method for preparing 1-(4-methanesulfonamidophenoxy)-2-[N-(4-methanesulfonamidophenethyl)-N-methylamino]ethane (Dofetilide) of formula I by sulfonylation of 1-(4-aminophenoxy)-2-[N-(4-aminophenethyl)-N-methylamino]ethane of formula II with N-methylsulfonyl-N′-methylimidazolium chloride of formula III.
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Paragraph 0023
(2019/06/17)
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- Mild Pd-catalyzed N -arylation of methanesulfonamide and related nucleophiles: Avoiding potentially genotoxic reagents and byproducts
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A convenient, general, and high yielding Pd-catalyzed cross-coupling of methanesulfonamide with aryl bromides and chlorides is reported. The use of this method eliminates concern over genotoxic impurities that can arise when an aniline is reacted with methanesulfonyl chloride. The application of this method to the synthesis of dofetilide is also reported.
- Rosen, Brandon R.,Ruble, J. Craig,Beauchamp, Thomas J.,Navarro, Antonio
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supporting information; experimental part
p. 2564 - 2567
(2011/06/25)
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- Computer-aided design, synthesis and biological assay of p-methylsulfonamido phenylethylamine analogues
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Class III antiarrhythmic agents selectively delay the effective refractory period (ERP) and increase the transmembrance action potential duration (APD). Based on our previous studies, a set of 17 methylsulfonamido phenylethylamine analogues were investigated by 3D-QSAR techniques of CoMFA and CoMSIA. The 3D-QSAR models proved a good predictive ability, and could describe the steric, electrostatic and hydrophobic requirements for recognition forces of the receptor site. According to the clues provided by this 3D-QSAR analysis, we designed and synthesized a series of new analogues of methanesulfonamido phenylethylamine (VI(a-i)). Pharmacological assay indicated that the effective concentrations of delaying the functional refractory period (FRP) 10ms of these new compounds have a good correlation with the 3D-QSAR predicted values. It is remarkable that the maximal percent change of delaying FRP in μM of compound VI(c) is much higher than that of dofetilide. The results showed that the 3D-QSAR models are reliable. (C) 2000 Elsevier Science Ltd.
- Liu, Hong,Ji, Min,Jiang, Hualiang,Liu, Ligang,Hua, Weiyi,Chen, Kaixian,Ji, Ruyun
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p. 2153 - 2157
(2007/10/03)
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- Dofetilide polymorphs
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PCT No. PCT/EP98/06641 Sec. 371 Date Nov. 16, 1999 Sec. 102(e) Date Nov. 16, 1999 PCT Filed Oct. 9, 1998 PCT Pub. No. WO99/21829 PCT Pub. Date May 6, 1999The invention relates to the substantially pure dofetilide polymorphs P162, P162a and P143, and to processes for the preparation of, compositions containing and to the uses of, such polymorphs.
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- Selective class III antiarrhythmic agents. 1. Bis(arylalkyl)amines
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A series of bis(arylalkyl)amines is described and their effects on prolonging effective refractory period in isolated cardiac tissue listed. Most compounds prolonged the cardiac action potential without significantly altering the maximum rate of depolarization and may be defined as selective class III antiarrhythmic agents. It was found that a particularly advantageous structural feature was to have a methanesulfonamido moiety on both of the aryl rings. Thus, compound 16 [1-(4-methanesulfonamidophenoxy)-2-[N-(4-methanesulfonamidophenethyl)- N-methylamine]ethane] was selected for further investigations. The compound is highly potent and selective class III agent which acts by blockade of cardiac potassium channels.
- Cross,Arrowsmith,Thomas,Gwilt,Burges,Higgins
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p. 1151 - 1155
(2007/10/02)
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- Anti-arrhythmic agents
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A series of [N-alkyl-N-(nitro-, alkylsulphonamido, or amino-phenalkyl)amino]-alkyl, alkoxy or alkylthio phenyl derivatives having utility as anti-arrhythmic agents.
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