Class III antiarrhythmic activity of novel substituted 4-[(methylsulfonyl)amino]benzamides and sulfonamides

Ellingboe, John W.; Spinelli, Walter; Winkley, Michael W.; Nguyen, Thomas; Parsons, Roderick W.; Moubarak, Issam F.; Kitzen, Jan M.; Engen, Donna Von; Bagli, Jehan F.

doi:10.1021/jm00082a011

Cited by 58 publications

(24 citation statements)

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“…Benzimidazoles and 2‐aminobenzimidazoles are very powerful compounds because of their applications in therapeutic and biological sciences (Figure ) . These compounds were used as neuropeptide YY1 receptor antagonist, N ‐methyl‐D‐aspartate (NMDA) antagonist, factor Xa(FXa) inhibitor, poly(ADP‐ribose)polymerase (PARP) inhibitor and non‐peptide thrombin inhibitor .…”

Section: Figurementioning

confidence: 99%

Synthesis of Benzimidazoles via Domino Intra and Intermolecular C‐N Cross‐Coupling Reaction

2018

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The synthesis of aminobenzimidazoles has been demonstrated under mild reaction conditions using cobalt catalyst in one pot reaction. This methodology involved domino intra and intermolecular C-N cross-coupling reaction. In addition, functional group tolerance has been also explored.Benzimidazoles [1][2][3][4][5][6][7][8][9][10] and 2-aminobenzimidazoles [11][12][13][14][15][16][17][18][19][20][21] are very powerful compounds because of their applications in therapeutic [22][23] and biological sciences ( Figure 1). [24][25] These compounds were used as neuropeptide YY1 receptor antagonist, [26] N-methyl-D-aspartate (NMDA) antagonist, [27] factor Xa(FXa) inhibitor, [28] poly(ADP-ribose)polymerase (PARP) inhibitor [29] and non-peptide thrombin inhibitor. [30] In addition, these compounds show anti-inflammatory, antimicrobial and antibacterial activities. [31] Apart from that, these compounds can also be used for the synthesis of dyes and high-temperature resistance polymers. [32] Therefore, the construction of benzimidazole derivatives were developed by many researchers via both traditional methods [33][34][35] and C-N cross-coupling reactions using various transition metals such as Cu, [36][37][38][39][40] Pd, [41][42][43] Co, [44] Zn, [45][46][47] and Ru. [48] In this connection, we would like to demonstrate the methodology for the synthesis of benzimidazoles from thiourea in one pot reaction via desulphurization/substitution/domino C-N cross-coupling reaction using cobalt source as catalyst under mild reaction conditions.

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Section: Figurementioning

confidence: 99%

Synthesis of Benzimidazoles via Domino Intra and Intermolecular C‐N Cross‐Coupling Reaction

2018

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“…15−17 Amination of 13a with 3-aminopropanol under neat conditions at high temperature afforded the highly polar intermediate 14a , which required extensive chromatography for purification. (18) It was found that conducting the amination reaction under solvent-free microwave heating conditions at 180 °C/25 min afforded 14a in high yield and purity after simple extraction.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Protein Kinase C-Driven Nuclear Factor-κB Activation: Synthesis, Structure−Activity Relationship, and Pharmacological Profiling of Pathway Specific Benzimidazole Probe Molecules

et al. 2010

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A unique series of biologically active chemical probes that selectively inhibit NF-κB activation induced by protein kinase C (PKC) pathway activators have been identified through a cell-based phenotypic reporter gene assay. These 2-aminobenzimidazoles represent initial chemical tools to be used in gaining further understanding on the cellular mechanisms driven by B and T cell antigen receptors. Starting from the founding member of this chemical series 1a (notated in PubChem as CID-2858522), we report the chemical synthesis, SAR studies, and pharmacological profiling of this pathway-selective inhibitor of NF-κB activation.

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“…16 Compounds containing this heterobicyclic nucleus exhibit therapeutic properties such as antiarrhythmic, 17 antihistaminic, 18 anticancer, 20 and antiviral, 21 to name just a few of them. In addition, benzimidazoles also show diverse biological activities as inhibitor of phosphodiesterase IV, 22 or antagonist of angiotensin II 23 and neuropeptide Y 24 receptors.…”

Section: Methodsmentioning

confidence: 99%

A Multicomponent Domino Reaction and in situ Aerobic Oxidation Sequence for the First One-Pot Synthesis of Polycyclic Benzimidazoles from 1,3-Dicarbonyl Derivatives

Liéby-Muller¹,

Simon²,

Imhof³

et al. 2006

Synlett

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A facile one-pot synthesis of functionalized pyrido[1,2-a]benzimidazoles is described via a molecular-sieves-promoted three-component domino reaction and in situ aerobic oxidation sequence from 1,3-dicarbonyls, aromatic o-diamines and unsaturated aldehydes. This environmentally friendly sequence does not require any harmful reagents, and liberates water as the only by-product. The desired products are obtained in good to excellent yields and generally with high purity, after simple filtration. Development of new multicomponent reactions 1 involving domino processes (MCRs), 2 combining at least three different substrates in a one-pot operation, constitutes nowadays a central academic and industrial investigation domain 3 in diversity-oriented synthesis 4 of functionalized heterocycles. These very efficient atom-5 and stepeconomic 6 transformations also combine increase in molecular and functional complexity with practical and environmental concerns, 7 approaching quite closely the concept of an ideal synthesis. 8 Although isonitriles became one of the most popular reactant in MCRs, 9 especially as a key component in the well-known Passerini 10 and Ugi 11 reactions, the reactivity of 1,3-dicarbonyls, proposed as early as 1882 by Hantzsch, 12 proved to be highly efficient but have been relatively unexplored until recently. 13 As part of our efforts to develop new efficient one-pot methodologies to access novel heterocyclic structures, we have recently reported molecular-sieves-promoted multicomponent domino transformations of b-keto esters, b-diketones and b-keto amides in the presence of unsaturated aldehydes and functionalized primary amines for the stereoselective synthesis of polycyclic N/O-, N/Sand N/N-aminals 14 or polyfunctionalized 2,6-diazabicyclo[2.2.2] octane cores 15 (Figure 1).Interestingly, in both approaches, although usually fused derivatives were obtained with simple aliphatic amines (Figure 1, compounds A-C), using o-hydroxyaniline resulted in the exclusive formation of spiro-type structures ( Figure 1, compounds D or E). On the contrary, a preliminary experiment indicated that the use of o-aminoaniline 3 led regioselectively to the corresponding fused polyheterocycles. As illustrated in Scheme 1, under standard conditions, reaction of b-keto ester 1a with acrolein 2a and 1,2-diaminobenzene 3 gave a 88% yield of a unexpected mixture of fused tricyclic aminal 4a and the corresponding benzimidazole 5a in a 1:1 ratio. Subsequent treatment of the crude mixture with CAN or MnO 2 afforded the oxidized compound 5a as a single product, opening a potential new way for the facile one-pot construction of benzimidazole nucleus. Scheme 1In this communication, we report a new and versatile multicomponent domino reaction and in situ aerobic oxidation sequence for the clean and efficient one-pot synthesis of functionalized polycyclic benzimidazole skeletons. Our approach is based on the peculiar selective reactivity of aromatic o-diamines which allows the exclusive formation of fused benzimidazoles by in situ o...

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Class III antiarrhythmic activity of novel substituted 4-[(methylsulfonyl)amino]benzamides and sulfonamides

Cited by 58 publications

References 1 publication

Synthesis of Benzimidazoles via Domino Intra and Intermolecular C‐N Cross‐Coupling Reaction

Synthesis of Benzimidazoles via Domino Intra and Intermolecular C‐N Cross‐Coupling Reaction

Inhibition of Protein Kinase C-Driven Nuclear Factor-κB Activation: Synthesis, Structure−Activity Relationship, and Pharmacological Profiling of Pathway Specific Benzimidazole Probe Molecules

A Multicomponent Domino Reaction and in situ Aerobic Oxidation Sequence for the First One-Pot Synthesis of Polycyclic Benzimidazoles from 1,3-Dicarbonyl Derivatives

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