Development of 3-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine derivatives as novel Mycobacterium tuberculosis pantothenate synthetase inhibitors.
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.
Antitubercular Drug Discovery Laboratory, Department of Pharmacy, Birla Institute of Technology and Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, India.
Ganesh
G
Samala
Parthiban Brindha
PB
Devi
Radhika
R
Nallangi
Perumal
P
Yogeeswari
Dharmarajan
D
Sriram
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010453:Peptide Synthases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C000589300:1-benzoyl-N-(4-nitrophenyl)-3-phenyl-6,7-dihydro-1H-pyrazolo(4,3-c)pyridine-5(4H)-carboxamide; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D010453:Peptide Synthases; C022318:pantothenate synthetase
Cytotoxicity; Pantothenate synthetase; Tuberculosis