Spiro- and substituted tetrahydrobenzo[b]thiophene-triazaphospholes and phosphoramidates as potent antineoplastic agents: synthesis, biological evaluation, and SAR studies

• Published in: Monatshefte für Chemie Vol. 147; no. 3; pp. 619 - 626
• Main Authors: Abdou, Wafaa M., Ganoub, Neven A., Sabry, Eman
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.03.2016; Springer Nature
• Subjects: Analytical Chemistry; Chemistry; Chemistry and Materials Science; Chemistry, Multidisciplinary; Chemistry/Food Science; Inorganic Chemistry; Organic Chemistry; Original Paper; Physical Chemistry; Physical Sciences; Science & Technology; Theoretical and Computational Chemistry; Azides; Phosphoramidates; Anticancer agents; Trialkyl phosphites; Triazaphospholes; Dialkyl phosphites; AMINO; CARBODIIMIDES; HETEROCYCLES; ESTERS; COUMARIN; PHOSPHITES; CYTOTOXICITY; DERIVATIVES
• ISSN: 0026-9247; 1434-4475
• DOI: 10.1007/s00706-015-1542-4

New and efficient conjugate addition reaction of trimethyl, triethyl, and triisopropyl phosphites with 2-azido-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3-carbonitrile was developed and furnished spiro-triazaphosphole-oxide derivatives in ≈70 % yield. Contrary to these results, linear substituted phosphoramidates were obtained from the reaction of the azide with dimethyl, diethyl, and diisopropyl phosphites. N -Alkylamino- or 2-aminotetrahydrobenzo[ b ]thiophene-3-carbonitrile was also isolated in ~10 % yield from the previous two reactions. In the context of this work, hexaalkylphosphorus triamides were caused to react with the same substrate afforded the corresponding phosphoric triamides only in the presence of a protonating agent (dil. alcohol). The three reactions proceeded smoothly, cleanly, and were completed within ~6 h at r.t. Pharmacological evaluation results of antibreast, anticolon, and antiprostate carcinoma cell lines properties for the products were discussed in terms of structure–activity relationship to define a chromophore for lead compounds. Graphical abstract