Exploration of 4-aminopyrrolo[2,3-d]pyrimidine as antitubercular agents

Exploration of 4-aminopyrrolo[2,3-d]pyrimidine as antitubercular agents. Jesumoroti, O. J., Beteck, R. M, Jordaan, A., Warner, D. F, & Legoabe, L. J Molecular Diversity, Springer, may, 2022.

Paper doi abstract bibtex

Tuberculosis (TB) is one of the leading causes of death worldwide. Developing new anti-TB compounds using cost-effective processes is critical to reduce TB incidence and accomplish the End TB Strategy milestone. Herein, we describe the synthesis and structure–activity relationships of a library of thirty 7H-Pyrrolo[2,3-d]pyrimidine derivatives providing insights into the contributions of different aromatic, aryl and alkyl substitution at the C-4 position of the 7-deazapurine ring. The minimum inhibitory concentration (MIC) of the compounds against the green fluorescent protein (GFP) reporter strain of Mycobacterium tuberculosis was assayed using the standard broth microdilution method, and cell toxicity was determined using the MTT assay. Sixteen compounds displayed in vitro activity against the GFP reporter strain of Mycobacterium tuberculosis with MIC90 values of 0.488–62.5 µM. This study highlights the most potent derivative, N-(4-phenoxy phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine with a MIC90 value of 0.488 µM and was non-cytotoxic to the Vero cell line. Moreover, all the potent compounds from this series have a ClogP value less than 4 and molecular weight \textless 400; thus, likely to maintain drug-likeness during lead optimisation.

@article{Jesumoroti2022,
abstract = {Tuberculosis (TB) is one of the leading causes of death worldwide. Developing new anti-TB compounds using cost-effective processes is critical to reduce TB incidence and accomplish the End TB Strategy milestone. Herein, we describe the synthesis and structure–activity relationships of a library of thirty 7H-Pyrrolo[2,3-d]pyrimidine derivatives providing insights into the contributions of different aromatic, aryl and alkyl substitution at the C-4 position of the 7-deazapurine ring. The minimum inhibitory concentration (MIC) of the compounds against the green fluorescent protein (GFP) reporter strain of Mycobacterium tuberculosis was assayed using the standard broth microdilution method, and cell toxicity was determined using the MTT assay. Sixteen compounds displayed in vitro activity against the GFP reporter strain of Mycobacterium tuberculosis with MIC90 values of 0.488–62.5 µM. This study highlights the most potent derivative, N-(4-phenoxy phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine with a MIC90 value of 0.488 µM and was non-cytotoxic to the Vero cell line. Moreover, all the potent compounds from this series have a ClogP value less than 4 and molecular weight {\textless} 400; thus, likely to maintain drug-likeness during lead optimisation.},
author = {Jesumoroti, Omobolanle Janet and Beteck, Richard M and Jordaan, Audrey and Warner, Digby F and Legoabe, Lesetja J},
doi = {10.1007/S11030-022-10453-1},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Jesumoroti et al. - 2022 - Exploration of 4-aminopyrrolo2,3-dpyrimidine as antitubercular agents.pdf:pdf},
isbn = {0123456789},
issn = {1573-501X},
journal = {Molecular Diversity},
keywords = {Biochemistry,OA,Organic Chemistry,Pharmacy,Polymer Sciences,Tuberculosis,fund{\_}not{\_}ack,general,original},
mendeley-tags = {OA,fund{\_}not{\_}ack,original},
month = {may},
pmid = {35598185},
publisher = {Springer},
title = {{Exploration of 4-aminopyrrolo[2,3-d]pyrimidine as antitubercular agents}},
url = {https://link.springer.com/article/10.1007/s11030-022-10453-1},
year = {2022}
}

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