Abstract:BY 1D AND 2D NMR. The synthesis and NMR analysis of seven new 4-(aryl)amino-5-carboethoxy-1,3-dimethyl-1H-pyrazolo[3,4b]pyridines (7-13) are described. The synthetic approach used involved the preparation of intermediates 5-aminopyrazol (4), the enamine derivative (5) and the 4-chloro-1H-pyrazolo[3,4b]pyridine (6). Compounds (7-13) were obtained by treatment of 6 with the desired aniline. The structures of new heterocyclic compounds and their precursors intermediates were assigned on the basis of spectral anal… Show more
Three series of 4-anilino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic esters were synthesized as part of a program to study potential anti-Leishmania drugs. These compounds were obtained by a condensation reaction of 4-chloro-1H-pyrazolo[3,4-b]pyridine with several aniline derivatives. Some of them were also obtained by an alternative pathway involving a Mannich-type reaction. The hydrophobic parameter, log P, was determined by shake-flask methodology, and using the Hansch-Fujita addictive hydrophobic fragmental constants. These compounds were tested against promastigote forms of Leishmania amazonensis. The very promising results showed the 3'-diethylaminomethyl-substituted compounds as the most active [IC50 = 0.39 (21) and 0.12 microM (22)]. Molecular modeling, using semiempirical AM1 method, predicted the most active compounds through the low-energy conformers superimposition on amodiaquine structure. QSAR equations, derived from the IC50 values against L. amazonensis, showed the hydrophobic (log P) and Sterimol steric (L and B2) parameters as most significant contributions on biological activity.
Three series of 4-anilino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic esters were synthesized as part of a program to study potential anti-Leishmania drugs. These compounds were obtained by a condensation reaction of 4-chloro-1H-pyrazolo[3,4-b]pyridine with several aniline derivatives. Some of them were also obtained by an alternative pathway involving a Mannich-type reaction. The hydrophobic parameter, log P, was determined by shake-flask methodology, and using the Hansch-Fujita addictive hydrophobic fragmental constants. These compounds were tested against promastigote forms of Leishmania amazonensis. The very promising results showed the 3'-diethylaminomethyl-substituted compounds as the most active [IC50 = 0.39 (21) and 0.12 microM (22)]. Molecular modeling, using semiempirical AM1 method, predicted the most active compounds through the low-energy conformers superimposition on amodiaquine structure. QSAR equations, derived from the IC50 values against L. amazonensis, showed the hydrophobic (log P) and Sterimol steric (L and B2) parameters as most significant contributions on biological activity.
“…High resolution mass spectra (EI-70eV) were performed on a Varian MAT CH7 8500 direct inlet instrument. The Clsubstituted pyrazolo [3,4-b]pyridine (4a-c) [21][22][23][24] and aminoalkylphosphoramidates (7a-d) 25,26 compounds were prepared as previously reported.…”
Twelve new 1H-pyrazolo [3,4-b]pyridine phosphoramidate derivatives were synthesized under mild conditions by nucleophilic aromatic substitution reaction of aminoalkylphosphoramidates over 4-Cl substituted pyrazolo [3,4-b]pyridine in good yields. The new compounds were characterized by IR, 1 H, 13 C and 31 P NMR spectroscopy and HRMS. The crystal structure of one compound was solved by X-ray diffraction and showed a network of intermolecular interactions involving phosphoramidate groups.
“…31 Nucleophilic aromatic substitution by amines has been used as a versatile route to new pyrazolopyridine derivatives. 2,8,32,33 An halogen atom such as chlorine in the C-4 position as the leaving group and an ester or cyano group in the C-5 position as the withdrawing group propitiate the 1H-pyrazolo [3,4- with excess of the aminoalkylphosphoramidates (13a-e) in THF at 90 °C to obtain three series of substituted 1H-pyrazolo[3,4-b]pyridine phosphoramidates (14a-e, 15a-e and 16a-e) as solids in 67-83% yield (Scheme 2).…”
In this research three series of substituted 1H-pyrazolo[3,4-b]pyridine phosphoramidates were synthesized and characterized by infrared, 1 H, 13 C, and 31 P nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. The products were obtained in good yields (67-83%) under mild conditions by nucleophilic aromatic substitution reaction of aminoalkylphosphoramidates over 4-chloro-1H-pyrazolo[3,4-b]pyridines. These compounds were evaluated as antileishmanials against Leishmania amazonensis promastigotes in vitro. Among all, compounds of a series showed expressive antileishmanial activity. Two of them emerged as the most active, with IC 50 values of 6.44 ± 1.49 and 12.25 ± 0.68 µM. The cytotoxicity of this series was assessed on murine cells and presented values similar to the reference drug pentamidine.
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