Synthesis and DSC study a new pyridinedicarboximide diones derivatives, obtained under various conditions

Abstract

The series of three 4-alkoxy-2-[2-hydroxy-3-(4-aryl-1-piperazinyl)propyl]-6-methyl-1H-pyrrolo [3,4-c] pyridine-1,3(2H)-diones were synthesized. The structures of all formed compounds were identified by elemental analysis, FTIR, and 1 H NMR. The synthesized compounds were studied using differential scanning calorimetry and thermogravimetric analysis in order to determine the existence of multiple solid-state forms. Our measurements showed that the solvent, mechanical treatment, and quenching are the important factors. Two stable and one metastable modification were detected. Additionally, DFT calculations were performed.

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

“…In order to screen the compounds for analgesic activity, two screening methods were chosen: the "writhing" test ( Table 3 and Table S1) and the "hot plate" test (Table 4). All tested derivatives (8)(9)(10)(11)(12)(13)(14)(15) were active in the "writhing" test (ED 50 = 3.25-19.2 mg/kg), and their analgesic properties in this study exceeded the effect of aspirin (ED 50 = 39.15 mg/kg). In addition, for two imides, they were similar to morphine activity (9 = 3.25 mg/kg, 11 = 3.67 mg/kg, morphine = 2.44 mg/kg).…”

“…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].…”

“…In the next step, N-halogenalkylimides 5-7, were condensed with the appropriate cyclic amines: morpholine (8), phenylpiperazine (9,10), 2-methoxyphenylpiperazine (11,12).…”

“…Compound 11 also prolonged the latency time by 105%, but in one 400 mg/kg dose only. For the tested derivatives, ED 50 values were not determined, due to the non-significant effect in this test (8,10,(12)(13)(14)(15) or activity that did not fulfill the requirements for the proper calculations of the value (derivative 9 and 11). The ED 50 values for the reference compounds were 266.7 mg/kg (±SEM = 98.26; 148.2-533.4) and 2.55 mg/kg (± SEM = 0.63; 1.59-4.08) for ASA and morphine, respectively.…”