Development of 3-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine derivatives as novel Mycobacterium tuberculosis pantothenate synthetase inhibitors

• DOI: 10.1016/j.ejmech.2013.08.036
• Publication Date: 2013-09-12T14:32:34Z
• Authors: Ganesh Samala; Parthiban Brindha...; Radhika Nallangi; Perumal Yogeeswari; Dharmarajan Sriram
• Keywords: 0301 basic medicine; Dose-Response Relationship, Drug; Molecular Structure; Pyridines; Mycobacterium tuberculosis; Cell Line; 3. Good health; Mice; Structure-Activity Relationship; 03 medical and health sciences; Animals; Pyrazoles; Enzyme Inhibitors; Peptide Synthases; Cell Proliferation

Forty 3-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine derivatives were synthesized from piperidin-4-one by five step synthesis and evaluated for Mycobacterium tuberculosis (MTB) pantothenate synthetase (PS) inhibition study, in vitro activities against MTB, cytotoxicity against RAW 264.7 cell line. Among the compounds, 1-benzoyl-N-(4-nitrophenyl)-3-phenyl-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxamide (6ac) was found to be the most active compound with IC₅₀ of 21.8 ± 0.8 μM against MTB PS, inhibited MTB with MIC of 26.7 μM and it was non-cytotoxic at 50 μM.