A highly atom economic, chemo-, regio- and stereoselective synthesis and evaluation of spiro-pyrrolothiazoles as antitubercular agents.
The 1,3-dipolar cycloaddition of azomethine ylides derived from substituted isatins and 1,3-thiazolane-4-carboxylic acid to a series of 1-methyl-3,5-bis[(E)-arylmethylidene]-tetrahydro-4(1H)-pyridinones afforded novel spiro-pyrrolothiazoles chemo-, regio- and stereoselectively in quantitative yields. These compounds were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug resistant M. tuberculosis (MDR-TB) using agar dilution method. Among the synthesized compounds, spiro[5.3'']-5''-nitrooxindole-spiro-[6.3']-1'-methyl-5'-(2,4-di-chlorophenylmethylidene)tetrahydro-4'(1H)-pyridinone-7-(2,4-dichlorophenyl)tetra-hydro-1H-pyrrolo[1,2-c][1,3]thiazole (9k) was found to be the most active with a minimum inhibitory concentration (MIC) of 0.6microM against MTB and MDR-TB.
Karthikeyan
Subramanian Vedhanarayanan
SV
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625 021, India.
Bala
Balasubramanian Devi
BD
Raja
Velanganni Paul Alex
VP
Perumal
Subbu
S
Yogeeswari
Perumal
P
Sriram
Dharmarajan
D
D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011758:Pyrroles / Q000737:chemistry*; D013141:Spiro Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000995:Antitubercular Agents; D011758:Pyrroles; D013141:Spiro Compounds; D013844:Thiazoles