The Synthesis of 4-Hydroxyquinolines.<sup>1</sup> I. Through Ethoxymethylenemalonic Ester

Price, Charles C.; Roberts, Royston M.

doi:10.1021/ja01211a020

Cited by 119 publications

(72 citation statements)

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“…Price and Roberts [226] researched on pyrimidopyrimidines (77) (Fig. 74), while Erickson [227] alkylated anilines to obtain derivatives of quinoline (78-79) (Fig.…”

Section: Cyclization Via Ester Groupmentioning

confidence: 99%

EMCA and DEEM as Michael Reagents Used in Organic Synthesis

Kaczor¹,

Matosiuk

2005

COC

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“…Price and Roberts [226] researched on pyrimidopyrimidines (77) (Fig. 74), while Erickson [227] alkylated anilines to obtain derivatives of quinoline (78-79) (Fig.…”

Section: Cyclization Via Ester Groupmentioning

confidence: 99%

EMCA and DEEM as Michael Reagents Used in Organic Synthesis

Kaczor¹,

Matosiuk

2005

COC

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“…The 4-hydroxyquinolines, 20 in turn, can be readily made from quinolones via the Gould-Jacobs method. 21,22 Our one-J. Braz.…”

Section: Resultsmentioning

confidence: 99%

A mild and efficient method for the preparation of 3-(2'-Aminoaryl)pyrazoles from 4-chloroquinolines

Borges¹,

Oliveira²,

Pinheiro³

et al. 2007

J. Braz. Chem. Soc.

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Um método mais suave e eficiente é descrito para a síntese de 3-(2'-aminoaril)pirazóis, a partir das reações de 4-cloroquinolinas com hidrazina em excelentes rendimentos. Estas reações de abertura de anel heterocíclico ocorrem em condições mais suaves do que as descritas anteriormente.We describe a mild and efficient method for the formation of 3-(2'-aminoaryl)pyrazoles in excellent yields from reactions of 4-chloroquinolines with hydrazine. These heterocyclic ring opening reactions occur under much milder conditions then previously described.

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“…These were prepared in two different ways (see supplementary Schemes S1 and S2). 24,[35][36][37] In most cases, the starting materials were 3-X-anilines (X = CH 3 , CN, NO 2 or OCH 3 ) and diethyl ethoxymethylenemalonate which were heated in equimolar ratio at 110 C for 45 -60 min to yield a diethyl 2-((3-Xphenylamino)methylene)malonate. This was then cyclized to a corresponding ethyl-4-hydroxy-7-X-quinoline-3-carboxylate by refluxing in diphenyl ether (265 C) for 30 -60 min.…”

Section: Synthesismentioning

confidence: 99%

Structure–activity relationships for ferriprotoporphyrin IX association and β-hematin inhibition by 4-aminoquinolines using experimental and ab initio methods

Nsumiwa

Kuter

Wittlin

et al. 2013

Bioorganic & Medicinal Chemistry

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In order to probe structure-activity relationships of association with ferriprotoporphyrin IX (log K) and inhibition of -hematin formation, a series of 4-aminoquinolines with varying substituents at the 7-position (X) have been synthesized. These have been further elaborated by introduction of two different R groups on the 4-amino nitrogen atom in the form of methyl (R = Me) and ethylamine (R = EtNH 2 ) side chains. Data for a previously investigated series containing an N,N-diethyl-ethylamine side chain were also compared with the findings of this study. Experimentally, log K values for the simple 4-aminoquinoline series (R = H) were found to correlate with the hydrophobicity constant () of the group X. The log K values for the series with R = Me and EtNH 2 were found to correlate with those of the series with R = H. The log of the 50% -hematin inhibitory activity (log BHIA 50 ) was found to correlate with log K and either meta ( m ) or para ( p ) Hammett constants for the series with R = Me and EtNH 2 , but not the simple series with R = H. To further improve predictability, correlations with ab initio electrostatic parameters, namely Mulliken and CHelpG charges were investigated. The best correlations were found with CHelpG charges which indicated that log K values can be predicted from the charges on atom H-8 and the group X in the quinolinium species computed in vacuum, while log BHIA 50 values can be predicted from the CHelpG charges on C-7, C-8 and N-1 for the neutral species in vacuum. These correlations indicate that association and inhibition of -hematin formation are separately determined. They also suggest that electron withdrawing groups at the 7-position, but not necessarily hydrophobic groups are required for hemozoin inhibition. The upshot is that the correlations imply that considerably more hydrophilic hemozoin inhibitors are feasible.Keywords: hemozoin; DFT; antimalarials; quinolines; structure-activity relationships; ferriprotoporphyrin IX 3 IntroductionQuinoline antimalarials such as quinine and chloroquine have had a long and successful history. 1 Subsequent emergence of chloroquine resistance has led to the use of other quinoline derivative antimalarials such as mefloquine and amodiaquine. Indeed, the development and clinical deployment of new quinoline antimalarials continues to this day.For example, piperaquine, a bis-4-aminoquinoline effective against chloroquine-resistant strains that consists of two 4-aminoquinoline moieties attached by a linker has only recently been introduced into clinical use. 2 Ferroquine, a 4-amino-7-chloroquinoline with a ferrocenyl side-chain is currently in phase IIB clinical trials. 3 In addition, research on new quinoline antimalarials retains considerable interest, such as that on so-called "reversed chloroquines"and related compounds that are both antimalarially active and inhibit the chloroquine resistance mechanism of the parasite. 4-10The class of 4-aminoquinoline antimalarials are believed to act by inhibiting the incorporation of ferrih...

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The Synthesis of 4-Hydroxyquinolines.¹ I. Through Ethoxymethylenemalonic Ester

Cited by 119 publications

References 0 publications

EMCA and DEEM as Michael Reagents Used in Organic Synthesis

EMCA and DEEM as Michael Reagents Used in Organic Synthesis

A mild and efficient method for the preparation of 3-(2'-Aminoaryl)pyrazoles from 4-chloroquinolines

Structure–activity relationships for ferriprotoporphyrin IX association and β-hematin inhibition by 4-aminoquinolines using experimental and ab initio methods

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The Synthesis of 4-Hydroxyquinolines.1 I. Through Ethoxymethylenemalonic Ester

Cited by 119 publications

References 0 publications

EMCA and DEEM as Michael Reagents Used in Organic Synthesis

EMCA and DEEM as Michael Reagents Used in Organic Synthesis

A mild and efficient method for the preparation of 3-(2'-Aminoaryl)pyrazoles from 4-chloroquinolines

Structure–activity relationships for ferriprotoporphyrin IX association and β-hematin inhibition by 4-aminoquinolines using experimental and ab initio methods

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The Synthesis of 4-Hydroxyquinolines.¹ I. Through Ethoxymethylenemalonic Ester