Synthesis and in-vitro antimycobacterial evaluation of 1-(cyclopropyl/2,4-difluorophenyl/tert-butyl)-1,4-dihydro- 8-methyl-6-nitro-4-oxo-7-(substituted secondary amino)quinoline-3-carboxylic acids.
Fifty one newer 1-(cyclopropyl/2,4-difluorophenyl/tert-butyl)-1,4-dihydro-8-methyl-6-nitro-4-oxo-7-(substituted secondary amino)quinoline-3-carboxylic acids were synthesized from 1,3-dichloro-2-methylbenzene and evaluated for in-vitro antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC(2)). Among the synthesized compounds, 1-cyclopropyl-1,4-dihydro-7-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)-8-methyl-6-nitro-4-oxoquinoline-3-carboxylic acid 9p was found to be the most active compound in vitro with a MIC value of 0.39 microM against MTB. Against MDR-TB, compound 7-(2-carboxy-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-1-cyclopropyl-1,4-dihydro-8-methyl-6-nitro-4-oxoquinoline-3-carboxylic acid 9n was found to be the most active with a MIC value of 0.09 microM.
Senthilkumar
Palaniappan
P
Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Pilani, India.
Dinakaran
Murugesan
M
Chandraseakaran
Yogesh
Y
Yogeeswari
Perumal
P
Sriram
Dharmarajan
D
D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002073:Butanes / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D005464:Fluorobenzenes / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D020102:Mycobacterium smegmatis / Q000187:drug effects* / Q000254:growth & development; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship; D014709:Vero Cells
C539952:1-cyclopropyl-1,4-dihydro-7-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)-8-methyl-6-nitro-4-oxoquinoline-3-carboxylic acid; C539953:7-(2-carboxy-5,6-dihydroimidazo(1,2-a)pyrazin-7(8H)-yl)-1-cyclopropyl-1,4-dihydro-8-methyl-6-nitro-4-oxoquinoline-3-carboxylic acid; D000995:Antitubercular Agents; D002073:Butanes; D005464:Fluorobenzenes; D011719:Pyrazines; D011804:Quinolines; C046888:butane