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

Abstract

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-Alkylaminoor 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

Synthesis and Crystal Structure of a New Hydrated Benzimidazolium Salt Containing Spiro Structure

“…As an important type of heterocycles, spiro compounds that contain one common atom have also shown prominent biological and pharmacological properties, such as antimicrobial [1,2], anticancer [3,4], antioxidant [5], anti-tubercular agents [6], protease activated receptor-1 (PAR1) antagonist [7], antineoplastic [8], and so on. In the last decade, the researchers' interests are now shifted to the salts of heterocyclic compounds in order to increase their solubility and efficacy.…”

Crystal structure of 8-(3,4-dimethylbenzylidene)-6,10-dioxaspiro[4.5]decane-7,9-dione, C17H18O4

“…Spiro compounds and their derivatives have been extensively studied due to their diverse biological application in antitumor [5], cytotoxic [6] antimicrobial [7], antioxidant [8], antineuroinflammatory [9] and antineoplastic [10]. In recent years, application of spiro compounds in optical fields such as organic semiconductor [11], fluorescent switches [12] and deep-blue emitting materials [13] has also received much attention.…”

Synthesis of Novel Coumarin Derivatives Bearing Phosphor Ester Motifs and Evaluation of their Antioxidant Activities

“…The attention in coumarin derivative chemistry and the biological activities of these compounds has increased through the previous five decades. In follow up to our lab research plan that pointed to the utility of phosphorus reagents in pharmaceuticals synthesis [18][19][20][21][22][23][24][25][26][27][28][29], we expand the previous work on phosphor reagents and coumarins [30,31] to produce unprecedented coumarin derivatives of prospective biological activities, particularly as antioxidants. The methodology depends on the reaction of azidochromene carbaldehyde 1 and 4-azidocoumarin (16) with trialkyl phosphites 2a-c, dialkyl phosphites 7a-c, and hexaalkylphosphorus triamides 11a,b.…”