Iodine-mediated one-pot intramolecular decarboxylation domino reaction for accessing functionalised 2-(1,3,4-oxadiazol-2-yl)anilines with carbonic anhydrase inhibitory action

Journal of Enzyme Inhibition and Medicinal Chemistry

Krishnan Rangan¹  Narayana Nagesh²  P. V. Sri Ramya³  Rohini Sodhi³  Mohammed Arifuddin³  Srinivas Angapelly³  Andrea Angeli⁴  Claudiu T. Supuran⁴ 

[1] Birla Institute of Technology & Science, Pilani, Hyderabad, India;Center for Cellular and Molecular Biology (CCMB), Hyderabad, Indi;National Institute of Pharmaceutical Education and Research (NIPER) – Hyderabad, Hyderabad, India;Neurofarba Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, University of Florence, Florence, Italy;

关键词: Domino synthesis;    1,3,4-oxadiazole;    carbonic anhydrase;    sulphonamide;    iodine;   

DOI  :  10.1080/14756366.2018.1443447

来源: publisher

【 摘 要 】

A practical and transition metal-free one-pot domino synthesis of diversified (1,3,4-oxadiazol-2-yl)anilines has been developed employing isatins and hydrazides as the starting materials, in the presence of molecular iodine. The prominent feature of this domino process involves consecutive condensation, hydrolytic ring cleavage, and an intramolecular decarboxylation, in a one-pot process that leads to the oxidative formation of a C–O bond. Fluorescence properties of some of the representative molecules obtained in this way were studied. The synthesised 2-(1,3,4-oxadiazolo-2-yl)aniline-benzene sulphonamides (8a–o) were screened for their carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity. Most of the compounds exhibited low micromolar to nanomolar activity against human (h) isoforms hCA I, hCA II, hCA IV, and XII, with some compounds displaying selective CA inhibitory activity towards hCA II with KIs of 6.4–17.6 nM.

【 授权许可】

CC BY