Synthesis and antimycobacterial activities of non-purine analogs of 6-aryl-9-benzylpurines; imidazopyridines, pyrrolopyridines, benzimidazoles and indoles
Journal article, Peer reviewed
N o t i c e: this is the author’s version of a work that was accepted for publication in bioorganic & medicinal chemistry. changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. changes may have been made to this work since it was submitted for publication. a definitive version was subsequently published in bioorganic & medicinal chemistry, 19, 2011. http://dx.doi.org/10.1016/j.bmc.2011.04.023
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Original versionKhoje, A.D., Charnock, C., Wan, B., Franzblau, S. & Gundersen, L-L. (2011). Synthesis and antimycobacterial activities of non-purine analogs of 6-aryl-9-benzylpurines; imidazopyridines, pyrrolopyridines, benzimidazoles and indoles. Bioorganic & Medicinal Chemistry, 19, 3483-3491 http://dx.doi.org/10.1016/j.bmc.2011.04.023
6,9-Disubstituted purines and 7-deazapurines are known to be powerful inhibitors of Mycobacterium tuberculosis (Mtb) in vitro. Analogs modified in the six-membered ring (imidazopyridines, pyrrolopyridines, benzimidazoles, and indoles) were synthesized and evaluated as Mtb inhibitors. The targets were prepared by functionalization on the bicyclic heterocycle or from simple pyridines. The results reported herein, indicate that the purine N-1, but not N-3, is important for binding to the unknown target. The 3-deazapurines appears to be slightly more active compared to the parent purines and slightly less active than their 7-deazapurine isomers. Removal of both the purine N-3 and N-7 did not result in further enhanced antimycobacterial activity but the toxicity towards mammalian cells was increased. Both 3-deaza and 3,7-dideazapurines exhibited a modest activity against of the Mtb isolate in the state of non-replicating persistence.