Novel pharmacological activity of a series of substituted pyridines

Butler, Donald E.; Bass, Paul; Nordin, Ivan C.; Hauck, Frederick P.; L'Italien, Yvon J.

doi:10.1021/jm00289a005

Cited by 30 publications

(4 citation statements)

References 4 publications

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“…44 The reaction could also be applied to hydroquinone and resorcine, which reacted with pyridinium salt 2a to give the pyridine ethers 8a,b and 9a,b, respectively (Scheme 5). These compounds constitute chlorine-substituted derivatives of pharmacologically interesting agents such as gastric acid inhibitors, 45 monoamine oxidase model substrates, 46 and structures related to nimesulide. 47 Other derivatives have also been patented.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of Functionalized Pyridines by Substitution of Hetarenium-Activated Pentachloropyridine with Bisnucleophiles

Schmidt¹,

Mordhorst²,

Nieger³

2006

Synthesis

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Pyridines, acting as heteroaromatic N-nucleophiles, 4-aminopyridine as an N,N-bisnucleophile, and 3,4-diaminopyridine as an N,N,N-trisnucleophile, all reacted with 4-(dimethylamino)-1-(2,3,5,6-tetrachloropyridin-4-yl)pyridinium chloride to give trispyridinio-substituted 3,5-dichloropyridines. Reaction of the same pyridinium chloride with O,O-bisnucleophiles such as 1,3-propanediol, hydroquinone, and resorcine, or the O,O,O-nucleophile phloroglucine, formed new Cl 2 ,Cl 3 ,O 4 ,Cl 5 ,Cl 6 and O 2 ,Cl 3 ,O 4 ,Cl 5 ,Cl 6 -substituted pyridines. S,O-Bisnucleophiles, such as 2-sulfanylethanol or 3-sulfanylpropionic acid gave the corresponding S-substituted pyridines (x-ray analysis). The (pyridin-4-yl)propionic acid was converted into bis(pyridinio)pyridine-4-thiol, an example of the rare class of N 2 ,Cl 3 ,S 4 ,Cl 5 ,N 6 -substituted pyridines.4-(Dimethylamino)pyridine (DMAP) and other nucleophilic heteroaromatics such as 4-(pyrrolidin-1-yl)pyridine and 1-methylimidazole are very valuable tools in organic synthesis. They play important roles as catalysts of organic reactions, as stabilizing substituents, and as activating groups for subsequent chemical reactions. Since Steglich and Höfle reported that DMAP effectively catalyzes acylation reactions, 1 its application for acylations of a broad variety of alcohols, amines, phenols, and enolates, 2,3 Baylis-Hillman 4 and Dakin-West reactions, 5 protection of amines, 6 C-acylations, 7 silylations, 3 and many other reactions have been described. Moreover, activation through a combination of DMAP and N,N¢-dicyclohexylcarbodiimide (DCC) was developed as an efficient method for esterifications, 8 nucleophilic asymmetric catalysis, 9 and reactions with polymeric DMAP reagents. 10 Streitwieser and co-workers reported that 4-(dimethylamino)pyridinium and other hetarenium substituents are able to stabilize reactive species such as the allyl anion 11 and the allyl radical. 12 We described stabilized uracilates, 13 pyrimidinium-olates, 14 pyrimidinium-aminides 15 and pyridinium-olates, 16 as well as hetarenium-substituted heteroaromatics which delocalize up to ten positive charges within a common p-electron system. 17 The activation of perhalogenated heteroaromatics by hetarenium substituents can be employed for the preparation of otherwise unavailable substituted heteroaromatics. As depicted in Scheme 1 for pyridines, 4-(dimethylamino)-1-(2,3,5,6-tetrachloropyridin-4-yl)pyridinium chloride (2a), readily available in almost quantitative yield from pentachloropyridine (1), 17 can be used to prepare Cl 2 ,Cl 3 ,O 4 ,Cl 5 ,Cl 6 -and O 2 ,Cl 3 ,O 4 ,Cl 5 ,Cl 6 -pentasubstituted pyridines 18 as well as their sulfur analogs. 19 Similarly, hitherto unavailable O 2 ,Cl 3 ,O 4 ,Cl 5 ,O 6 -16 and biologically interesting S 2 ,Cl 3 ,S 4 ,Cl 5 ,S 6 -pentasubstituted pyridines, 19 as well as a broad variety of symmetric and non-symmetric O 2 ,Cl 3 ,S 4 ,Cl 5 ,O 6 -pentasubstituted pyridines are available starting from 1. The procedure can be extended to the synthesis of the first representativ...

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Section: Methodsmentioning

confidence: 99%

Synthesis of Functionalized Pyridines by Substitution of Hetarenium-Activated Pentachloropyridine with Bisnucleophiles

Schmidt¹,

Mordhorst²,

Nieger³

2006

Synthesis

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“…6,7,11 In rare cases C-positions of the pyridine ring in 1[n] are substituted before further transformations. 16,24 In spite of the increasing use of 4-alkoxypyridines (1[n]; n ≥ 3), only a handful are well characterized (1 [3], 29,30 5 ), some have partial data (1[4], 19,24,28 1[5], 7,28 1[8] 23 , 1[16] 4 ), while others are only mentioned in the literature without any data (1[6]), 20,27 1[14], 12 1[18] 12,22 ) and several homologs are not reported (e.g. 1 [11], 1 [13] and 1 [15]).…”

Section: Figure 1 Structures Of 1[n] and 2[n]mentioning

confidence: 99%

“…[23][24][25] Some 4-alkoxypyridines 1[n] have been shown to exhibit biological activity, such as inhibition of cytochrome P-450-catalyzed aniline hydroxylation 26,27 or gastric antisecretory activity. 28…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 4-alkoxypyridines as intermediates for zwitterionic liquid crystals

Hajhussein¹,

Abuzahra²,

Pietrzak³

et al. 2018

Arkivoc

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A series of 4-alkoxypyridines with n = 5-18 was obtained in typical yields of 75-80% by reacting 4-chloropyridine hydrochloride with the appropriate alcohol in DMSO in the presence of powdered NaOH. The reported synthesis is compared to other methods for preparation of 4-alkoxypyridines, and their uses are reviewed. 4-Tridecyloxypyridine is converted into the bis-zwitterionic derivative of [closo-B10H10] 2-, which exhibits liquid crystalline and soft crystalline phases. The solid-state structures of two pyridines and the biszwitterion are established by the single crystal XRD method. The effect of N-atom coordination on the pyridine ring geometry is investigated.

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“…The current interest in 2-and 4-arylpyridines is based on their pharmacological activities and their potential usefulness as therapeutic agents for the treatment of various diseases. [1][2][3] They have been studied as cardiotonic agents, 4 gastric secretion inhibitors, 5 potential reactivators of acetylcholinesterase poisoned with organophosphorus compounds 6 and have been used as intermediates for the preparation of 6-arylpyridine semicarbazone insecticides. 7 During the course of chemical development activities, we became interested in 4-aryl-2-carboxypyridines and required a short synthesis that would allow making large quantities of compounds via an ecologically sound and safe process.…”

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confidence: 99%

The Palladium Catalysed Suzuki Coupling of 2- and 4-Chloropyridines

Lohse

1999

Synlett

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The Suzuki coupling of 2-and 4-chloropyridines with arylboronic acids is successfully performed under Pd(PPh 3 ) 4 catalysis. Moderate to good yields are obtained with 4-chloropyridines while 2-chloropyridines give excellent yields. The corresponding pyridine N-oxides react in the same manner. An easy and cheap access to arylpyridines, a class of compound with medicinal interest, is thus achieved.

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Novel pharmacological activity of a series of substituted pyridines

Cited by 30 publications

References 4 publications

Synthesis of Functionalized Pyridines by Substitution of Hetarenium-Activated Pentachloropyridine with Bisnucleophiles

Synthesis of Functionalized Pyridines by Substitution of Hetarenium-Activated Pentachloropyridine with Bisnucleophiles

Synthesis of 4-alkoxypyridines as intermediates for zwitterionic liquid crystals

The Palladium Catalysed Suzuki Coupling of 2- and 4-Chloropyridines

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Novel pharmacological activity of a series of substituted pyridines

Cited by 30 publications

References 4 publications

Synthesis of Functionalized Pyridines by Substitution of Hetarenium-Activated­ Pentachloropyridine with Bisnucleophiles

Synthesis of Functionalized Pyridines by Substitution of Hetarenium-Activated­ Pentachloropyridine with Bisnucleophiles

Synthesis of 4-alkoxypyridines as intermediates for zwitterionic liquid crystals

The Palladium Catalysed Suzuki Coupling of 2- and 4-Chloropyridines

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Synthesis of Functionalized Pyridines by Substitution of Hetarenium-Activated Pentachloropyridine with Bisnucleophiles

Synthesis of Functionalized Pyridines by Substitution of Hetarenium-Activated Pentachloropyridine with Bisnucleophiles