title: 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.
abstract: 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 AT(1) 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.
authors.affiliation: INSERM U761 Biostructures and Drug Discovery and Faculté de Pharmacie, Univ Lille Nord de France, 3 rue du Pr Laguesse, Lille F-59006, France. rebecca.deprez@univ-lille2.fr
authors.forename: Rebecca
authors.initials: R
authors.lastname: Deprez-Poulain
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cousaert
authors.forename: Patrick
authors.initials: P
authors.lastname: Toto
authors.forename: Nicolas
authors.initials: N
authors.lastname: Willand
authors.forename: Benoit
authors.initials: B
authors.lastname: Deprez
mesh_terms: D000081:Acetamides / Q000737:chemistry*; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011945:Receptors, Angiotensin / Q000187:drug effects; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000081:Acetamides; D011720:Pyrazoles; D011945:Receptors, Angiotensin