Synthesis and characterization of the atropisomeric relationships of a substituted N-phenyl-bipyrazole derivative with anti-inflammatory properties

• Published in: Chirality (New York, N.Y.) N.Y.), 2012-06, Vol.24 (6), p.463-470
• Main Authors: Veloso, Marcia P., Romeiro, Nelilma C., Silva, Gilberto M. S., Alves, Hélio De M., Doriguetto, Antonio C., Ellena, Javier, Miranda, Ana L. P., Barreiro, Eliezer J., Fraga, Carlos A. M.
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; atropisomerism; axial chirality; bipyrazole; celecoxib; Chromatography, High Pressure Liquid; Computer Simulation; COX inhibitors; Crystallography, X-Ray; Magnetic Resonance Spectroscopy; nonsteroidal anti-inflammatory drugs; Protein Binding - drug effects; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Stereoisomerism
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.22016

ABSTRACT This work describes the atropisomeric relationships of 3‐methyl‐5‐(3‐methyl‐5‐phenyl‐1H‐pyrazol‐1‐yl)‐1‐phenyl‐1H‐pyrazol‐4‐amine (2d), which belongs to series 4‐aminobipyrazole derivatives designed as anti‐inflammatory agents. The 1H nuclear magnetic resonance spectra obtained in the presence of a chiral lanthanide shift salt associated to chiral high‐performance liquid chromatography analysis, X‐ray diffraction, and molecular modeling tools confirmed that ortho bis‐functionalized bipyrazole 2d exists as a mixture of aR,aS‐atropisomers. These results provide useful information to understand the pharmacological profile of this derivative and of other 4‐aminobipyrazole analogs. Chirality 24:463–470, 2012. © 2012 Wiley Periodicals, Inc.