Quinolines. I. The Synthesis of 3-Methyl-4-(1'-methyl-4'-diethylaminobutyl-amino)-quinoline and Some 6-Substituted Derivatives

Steck, Edgar A.; Hallock, Louis L.; Holland, Arnold J.

doi:10.1021/ja01205a041

Cited by 12 publications

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“…The obtained 4-hydroxyquinolines 12a − p were subsequently chlorinated to 4-chloroquinolines 3a and 3c − q with thionyl chloride in the presence of N , N -dimethylformamide (DMF) . To obtain 4-chloro-3-methylquinoline 3r , the 4-hydroxy-3-methylquinoline-2-carboxylic acid ethyl ester 12p was hydrolyzed and decarboxylated to 12q before chlorination with phosphorus oxychloride . The 5,6,7,8-tetrahydroquinoline derivative 13 (Scheme ) was obtained by selective hydrogenation of the quinoline 12c in the presence of a nickel catalyst 21 to produce the corresponding 5,6,7,8-tetrahydroquinoline 12r , which was then chlorinated.…”

Section: Introductionmentioning

confidence: 99%

Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α_2C-Adrenoceptor Antagonists

Höglund¹,

Silver²,

Engström³

et al. 2006

J. Med. Chem.

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Starting from two acridine compounds identified in a high-throughput screening campaign (1 and 2, Table 1), a series of 4-aminoquinolines was synthesized and tested for their properties on the human alpha(2)-adrenoceptor subtypes (alpha(2A), alpha(2B), and alpha(2C)). A number of compounds with good antagonist potencies against the alpha(2C)-adrenoceptor and excellent subtype selectivities over the other two subtypes were discovered. For example, (R)-{4-[4-(3,4-dimethylpiperazin-1-yl)phenylamino]quinolin-3-yl}methanol 6j had an antagonist potency of 8.5 nM against, and a subtype selectivity of more than 200-fold for, the alpha(2C)-adrenoceptor. Investigation of the structure-activity relationship identified a number of structural features, the most critical of which was an absolute need for a substituent in the 3-position of the quinoline ring. The 3-position on the piperazine ring was also found to play an appreciable role, as substitutions in that position exerted a significant and stereospecific beneficial effect on the alpha(2C)-adrenoceptor affinity and potency. Replacing the piperazine ring proved difficult, with 1,4-diazepanes representing the only viable alternative.

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Section: Introductionmentioning

confidence: 99%

Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α_2C-Adrenoceptor Antagonists

Höglund¹,

Silver²,

Engström³

et al. 2006

J. Med. Chem.

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Synthesis of the Quinoline Ring System

Jones¹

1977

Chemistry of Heterocyclic Compounds: A Series of Monographs

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Haloquinolines

Smalley

1977

Chemistry of Heterocyclic Compounds: A Series of Monographs

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Quinolines. I. The Synthesis of 3-Methyl-4-(1'-methyl-4'-diethylaminobutyl-amino)-quinoline and Some 6-Substituted Derivatives

Cited by 12 publications

References 0 publications

Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α_2C-Adrenoceptor Antagonists

Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α_2C-Adrenoceptor Antagonists

Synthesis of the Quinoline Ring System

Haloquinolines

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Quinolines. I. The Synthesis of 3-Methyl-4-(1'-methyl-4'-diethylaminobutyl-amino)-quinoline and Some 6-Substituted Derivatives

Cited by 12 publications

References 0 publications

Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α2C-Adrenoceptor Antagonists

Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α2C-Adrenoceptor Antagonists

Synthesis of the Quinoline Ring System

Haloquinolines

Contact Info

Product

Resources

About

Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α_2C-Adrenoceptor Antagonists

Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α_2C-Adrenoceptor Antagonists