Abstract
New thieno[2,3-b]pyridine phosphoramidates compounds were synthesized and characterized by infrared; 1H, 13C, and 31P NMR spectroscopy; and high-resolution mass spectrometry. The products were obtained in good yields (64–82%) under mild conditions by nucleophilic aromatic substitution reaction of aminoalkylphosphoramidates over 4-chlorothieno[2,3-b]pyridine-5-carbonitrile. The crystal structures of two compounds were solved by x-ray diffraction and showed a network of intermolecular interactions involving phosphoramidate groups. Druglike properties and toxicity of the new compounds were studied with the help of the software Molinspiration, Osiris, and Toxtree, and were compared with the standard drugs amphotericin B, miltefosine, benznidazole, and nifurtimox.
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GRAPHICAL ABSTRACT
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ACKNOWLEDGMENTS
We thank Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenação de Aperfeiçamento de Pessoal de Nível Superior (CAPES) for financial support and the x-ray diffraction laboratory Laboratòrio de Difração de Raio-X da Universidade Federal Fluminense (LDRX-UFF) for data collection.
Notes
a x − 1, y, z.
b –x + 1, −y + 1, −z + 2.
a miLog P, Molinspiration-predicted log P; TPSA, total polar surface area; natoms, number of atoms; MW, molecular weight; nON, number of hydrogen-bond acceptors; nOHNH, number of hydrogen-bond donors; nrotb, number of rotatable bonds; and nviol, number of violations.