Discovery of novel antitubercular 2,10-dihydro-4aH-chromeno[3,2-c]pyridin-3-yl derivatives.
Twenty two novel 2,10-dihydro-4aH-chromeno[3,2-c]pyridin-3-yl derivatives were synthesized by reacting 3-formyl chromone, (sub)-2-amino pyridines, N1-(prop-2-ynyl)arylamides in the presence of indium triflate. The compounds were evaluated their preliminary in-vitro and in-vivo activity against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug resistant M. tuberculosis (MDR-TB). Among them N-[(4aS)-2-(3-methyl-2-pyridinyl)-10-oxo-2,10-dihydro-4aH-chromeno[3,2-c]pyridin-3-yl]methyl-4-ethylbenzenecarboxamide 4d was found to be the most active compound in-vitro with MIC's of 0.22 and 0.07 microg/mL against MTB and MDR-TB respectively. In the in-vivo animal model 4d decreased the bacterial load in lung and spleen tissues with 1.11 and 2.94-log10 protections respectively at 25 mg/kg body weight dose.
Sriram
Dharmarajan
D
Medicinal Chemistry & Antimycobacterial Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad-500 078, Andhra Pradesh, India. drdsriram@yahoo.com
Yogeeswari
Perumal
P
Dinakaran
Murugesan
M
Banerjee
Debjani
D
Bhat
Pritesh
P
Gadhwal
Sunil
S
D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002522:Chlorocebus aethiops; D055808:Drug Discovery; D008826:Microbial Sensitivity Tests; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D014709:Vero Cells
D000995:Antitubercular Agents; D011725:Pyridines; C023666:pyridine