Solid-phase synthesis of a library of pyrrolo[2,1-c][1,4]benzodiazepine-5,11-diones with potential antitubercular activity.
A versatile combinatorial approach was developed and utilized for the rapid synthesis of pyrrolo[2,1-c]-[1,4]benzodiazepine-5,11-dione (PBD-5,11-dione) libraries 10, 15, and 19 containing 210 compounds with varied substitutions in A, B, and C rings. The key aspect of the synthetic strategy includes Staudinger, intermolecular aza-Wittig reaction followed by imine reduction and base-mediated cyclative cleavage results in the formation of final resin-free compounds. This strategy provides a highly efficient and practical protocol for the parallel synthesis of PBD-5,11-diones on solid support. The modifications in the C-ring of the PBD scaffold produced three types of sublibraries. Reactions were monitored by FT-IR spectroscopy on the resin beads. Further, from a generated library of 210 compounds, 142 compounds have been selected and evaluated for in vitro activity against Mycobacterium tuberculosis, and some of these compounds have exhibited promising activity.
Kamal
Ahmed
A
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India. ahmedkamal@iict.res.in
Reddy
K Laxma
KL
Devaiah
V
V
Shankaraiah
N
N
Reddy
G Suresh Kumar
GS
Raghavan
Sadagopan
S
D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001570:Benzodiazepinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011392:Proline / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared
D000995:Antitubercular Agents; D001570:Benzodiazepinones; D011758:Pyrroles; D011392:Proline