Novel pyrrolo[2,3-d]pyrimidines and pyrrolo[2,3-b]pyridines: design, synthesis, and in vivo TNF-α inhibitory activity

Novel pyrrolo[2,3- d ]pyrimidines 5a – j , 6a – j and pyrrolo[2,3- b ]pyridines 7a – h ; incorporating the common vicinal diaryl motif of tumor necrosis factor-α (TNF-α) inhibitors, were synthesized starting from 2-amino-pyrrole-3-carbonitriles 1a – h . The structures of synthesized compounds were e...

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Bibliographic Details
Published in:Medicinal chemistry research 2015-05, Vol.24 (5), p.2097-2110
Main Authors: Hilmy, Khaled M. H., Abdul-Wahab, Hanan G., Soliman, Dalia H., Khalifa, Maha M. A., Hegab, Amany M.
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Original Research
Pharmacology/Toxicology
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Summary:Novel pyrrolo[2,3- d ]pyrimidines 5a – j , 6a – j and pyrrolo[2,3- b ]pyridines 7a – h ; incorporating the common vicinal diaryl motif of tumor necrosis factor-α (TNF-α) inhibitors, were synthesized starting from 2-amino-pyrrole-3-carbonitriles 1a – h . The structures of synthesized compounds were elucidated by spectral data (IR, NMR, and MS) and elemental analyses. Representative compounds were evaluated for their ability to inhibit lipopolysaccharide-induced TNF-α production in vivo in rat at 25 mg/kg p.o. Structure activity relationships are described. The pyrrolo[2,3- d ]pyrimidines displayed better inhibitory activity than the pyrrolo[2,3- b ]pyridines. The most potent among the biologically tested compounds was the pyrrolopyrimidine 5h ( N -(4-ethoxyphenyl)-2-(4-oxo-6-phenyl-7-(pyridine-4-yl)-4 H -pyrrolo[2,3- d ]pyrimidin-3(7 H )-yl)acetamide),showing TNF-α inhibitory activity (96 %) comparable to that of dexamethasone (91 %).
ISSN:1054-2523
1554-8120
DOI:10.1007/s00044-014-1281-9