Forced Degradation and Photodegradation Studies of Pyrrolo[3,4-c]pyridine-1,3-dione Derivatives as Analgesic Active Compounds Using HPLC, UV and IR Spectrometry, and HPLC/MS Methods

Abstract

The stress and accelerated tests as well as photostability analysis in solutions and the solid phase of three selected derivatives of pyrrolo[3,4-c]pyridine-1,3-dione were carried out according the International Conference on Harmonization guidelines. For observation of the degradation of tested compounds, the RP-HPLC method was used. The study included the effect of temperature, relative humidity, water, H+ and OH- ions, hydrogen peroxide, and light (6.0×10(6), 1.2×10(6) lux·h) on the stability of pyrrolo[3,4-c]pyridine-1,3-dione derivatives. Studies have shown that these derivatives are photolabile, extremely unstable in an alkaline medium, labile in an acidic medium, and stable in a neutral medium. Their sensitivity to oxidizing agents depends on the chemical structure. The shortening of the aliphatic chain leads to an increase in the sensitivity to hydrolytic and oxidizing factors. The presence of the 1,3,4-tetraisoquinoline group promotes an increase in the susceptibility to photodegradation. The introduction of a carbonyl group to the aliphatic chain and the tetrafluoromethyl group to the phenyl ring stabilizes the molecule in the case of hydrolysis and oxidation and also increases sensitivity to light. The analysis of observed photodegradation products using the HPLC-diode array detector, HPLC/MS, and UV and IR spectrometry techniques showed degradation targeted at the breaking of the pyrrolo[3,4-c]pyridine-1,3-dione, piperazine, and/or tetrahydroisoquinoline rings.

Bioresearch of New 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones

“…1A R= CH3 2A R= C2H5 The results were discussedin detail in our previous works [5][6][7][8][9][10][11][12][13][14]. As previously established, the shortening of the alkyl linker between the basic center of the arylamine and the cyclic imide moiety resulted in derivatives with similar biological properties [8].…”

“…The starting materials for the synthesis of compounds 9-15 were 4-methoxy-and 4-ethoxy-6methyl-1H-pyrrolo [3.4-c]pyridine-1,3(2H)-diones (3,4),and in the case of imide 8, it was an intermediate 4-methoxy-2,3-dihydro-6-methyl-2-(4-bromobutyl)-1,3-dioxo-1H-pyrrolo [3,4c]pyridine (5) synthesized previously [5,8]. The results were discussedin detail in our previous works [5][6][7][8][9][10][11][12][13][14]. As previously established, the shortening of the alkyl linker between the basic center of the arylamine and the cyclic imide moiety resulted in derivatives with similar biological properties [8].…”

Evaluation of 1,2-Benzothiazine 1,1-Dioxide Derivatives In Vitro Activity towards Clinical-Relevant Microorganisms and Fibroblasts

“…Synthesis and experimental data of compounds 2a – e and 3a – e were previously reported in [ 10 , 15 , 18 ], those of 4a – d and 5a – e were reported in [ 15 , 16 , 17 , 34 , 35 , 36 , 37 , 38 ]. Synthesis and experimental data of compounds 6a – g were described previously in [ 10 , 13 , 15 , 16 , 17 ].…”

Synthesis, COX-1/2 inhibition and antioxidant activities of new oxicam analogues designed as potential chemopreventive agents

“…Synthesis and experimental data for the 1-(2-chloro-1-oxoethyl)-4-arylpiperazine 6a-c compounds were previously reported (Szczęśniak-Sięga et al, 2014;Muszalska et al, 2015).…”

“…Then, the obtained 2a-d compounds were converted by Gabriel-Colman rearrangement into compounds 3a-d. Compounds 5a-d and 6a-c were also synthesized according to the previously described procedure (Lopez et al, 2010;Krzyżak et al, 2014;Maniewska et al, 2014;Muszalska et al, 2015;Paudel et al, 2016), by alkylation or acylation of the corresponding arylpiperazines. Whereas compound 7 was obtained in a reaction of chloroacetyl chloride with 2,3,4,9-tetrahydro-1H-β-carboline (Zhou et al, 2016).…”