Stability of New Derivative from the Mannich Base Group and the Review of the Studies on Stability of the Pyrrolo[3,4-c]pyridine-1,3(2H)-dione Derivatives Exhibiting Analgesic Activity

Abstract

For the evaluation of stability of the 2-(3,4-dihydro-1H-isoquinoline-2-yl-methyl)-4-methoxy-6-methylpyrrolo[3,4-c]pyridine-1,3-dione (V) in aqueous solutions (pH 0.39–12.2; 303 K, 308 K, 313 K, 318 K, 333 K, 343 K, 353 K, and 363 K) a HPLC-based method [LiChrosorb® RP-8 (250 × 4 mm, 5 µm); acetonitryle and 0.01 M phosphate buffer pH 2 (35:65); 240 nm] was developed. Determining the value of pK_a constant (2.8; 5.3; 9.2) and the thermodynamic parameters of the aforementioned reaction, the equation for the log k_pH in function of pH has been established. The lipophilicity coefficients of five pyrrolo[3,4-c]pyridine-1,3(2H)-dione were determined by the HPLC method.

Keywords:

• Hydrolysis
• Log P
• pyrrolo[3,4-c]pyridine-1,3(2H)-dione derivatives
• pK_a
• Stability

The authors wish to acknomledge Prof. H. Śladowska, D. Szkatuła, and A. Sabiniarz, Department of Chemistry of Drugs Wrocław University of Medicine for providing derivatives of pyrrolo[3,4-c]pyridine-1,3(2H)-dione (I–V) for the study. The study was supported by the 2008/09 research funds as a research project No. N N405 178535 (Ministry of Science and Higher Education, Poland).

Notes

; (∗the extrapolated values).