An Efficient Protocol for the Synthesis of 1, 5‐ disubstituted Tetrazole Derivatives via a TMS‐N3 Based Ugi Reaction and their Anti‐cancer Activity

• Published in: ChemistrySelect (Weinheim) 2018-11, Vol.3 (41), p.11657-11662
• Main Authors: Gohel, Jyoti N., Lunagariya, Kaushikkumar S., Kapadiya, Khushal M., Khunt, Ranjan C.
• Format: Article
• Language: English
• Subjects: Anti-cancer activity; Tetrazole; TMS-N3
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.201802638

In current research scenario, an efficient synthesis has been developed for novel tetrazole scaffolds by single step multicomponent reaction. One of the most promising pathways is Ugi multi‐component process for the coupling of four different components in a single reaction step and isolate lead molecule which may serve better life to the society. The syntheses of tetrazoles were undertaken by the Ugi‐Multi Component approach with the condensation of aromatic aldehyde containing active pharmacophore, various aryl amines, isocyanide (cyclohexyl isocyanide) and TMS‐N3 under catalyst free reaction condition at room temperature. The structural conformation were carried out by most acceptable spectroscopic technique i.e. MS, IR, NMR and single crystal study (XRD) and potency of compounds (4a to 4h) were checked at NIH (National Institute of Health) use 60 different cell‐lines with respect to nine cancer panels among which compounds 4a and 4b have been found to be more potent against different cell lines. N‐((1‐Cyclohexyl‐1H‐tetrazol‐5‐yl)(3‐(cyclopropylmethoxy)‐4‐(difluoromethoxy) phenyl)methyl) aniline derivatives have been synthesized via tetrazole Ugi‐4CR reaction. Characterization was carried out by various spectroscopic techniques like IR, NMR and Mass spectrometry and it is further supported by single crystal XRD method. Synthesized products have been evaluated for their in vitro anticancer activity against NCI‐60 cancer cell lines.