Application of Ullmann and Ullmann-Finkelstein reactions for the synthesis of N-aryl-N-(1H-pyrazol-3-yl) acetamide or N-(1-aryl-1H-pyrazol-3-yl) acetamide derivatives and pharmacological evaluation

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• 作者：Rebecca Deprez-Poulain^a ; ^b ; ^c ; ^d ; ^{rebecca.deprez@univ-lille2.fr} ; Nicolas Cousaert^a ; ^b ; ^c ; ^d ; Patrick Toto^a ; ^b ; ^c ; ^d ; Nicolas Willand^a ; ^b ; ^c ; ^d ; Benoit Deprez^a ; ^b ; ^c ; ^d ; ^{benoit.deprez@univ-lille2.fr}
• 关键词：Ullmann ; Ullmann&ndash ; Finkelstein ; Copper-catalyzed ; AT1-receptor antagonists ; Pyrazoles. C to N bioisosterism ; Patent escaping
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：September, 2011
• 年：2011
• 卷：46
• 期：9
• 页码：3867-3876
• 全文大小：566 K

文摘

Ullmann-type reactions are becoming a major tool in medicinal chemistry. In this article, we describe the use of these Copper-catalyzed reactions with various precursors, acyl-heteroarylamines or pyrazoles of interest for pharmacomodulation. To the medicinal chemist they offer new, usually untapped disconnection approaches to compounds of interest. They thus open the way to new original analogues of bioactive compounds possibly not patented, from common building-blocks. They also allow C to N bioisosteric replacements, which sometimes are synthetically challenging. We report for the first time the critical effect of acetylamino substituents on the regioselective arylation of unsymmetrical pyrazoles that are useful for medicinal chemists. Finally, we have applied this strategy to the design of novel AT₁ receptor antagonists. Though this family has been extensively investigated in the past 30 years, N-arylation and C to N replacement made possible by Ullmann chemistry, can produce original antagonists.