Azide based routes to tetrazolo and oxadiazolo derivatives of pyrrolobenzodiazepines and pyrrolobenzothiadiazepines |
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Authors: | Karl Hemming Christopher S Chambers Muslih S Hamasharif Heidi João Musharraf N Khan Nilesh Patel Rachel Airley Sharn Day |
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Institution: | 1. Department of Chemical Sciences, University of Huddersfield, Huddersfield HD1 3DH, United Kingdom;2. Department of Pharmacy, University of Huddersfield, Huddersfield HD1 3DH, United Kingdom |
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Abstract: | Tetrazolo- and 1,2,4-oxadiazolo-fused derivatives of the antitumour, antibiotic, DNA-interactive pyrrolo2,1-c]1,4]benzodiazepines and their pyrrolobenzothiadiazepine derivatives have been produced as analogues of a 1,2,3-triazolo-fused pyrrolobenzothiadiazepine, which was shown to be a Glut-1 transporter inhibitor with potential as an antitumour agent. The tetrazolo-fused systems were produced by intramolecular 1,3-dipolar cycloaddition between an azide and a nitrile. The 1,2,4-oxadiazolo systems were produced by nitrile oxide cycloadditions to pyrrolobenzothiadiazepines, which were in turn produced from a 2-(azidobenzenesulfonyl)-1,2-thiazine 1-oxide. The latter species underwent a phosphite-mediated one-pot sulfur-extrusion, ring-contraction and azide to amine conversion to form 1-(aminobenzenesulfonyl)pyrroles. Bischler–Napieralski ring closure gave the pyrrolobenzothiadiazepines. |
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Keywords: | Pyrrolobenzodiazepine Pyrrolobenzothiadiazepine Tetrazole 1 2 4-Oxadiazole Glut-1 inhibitor Pyrrole synthesis |
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