Carbodiimides in the Synthesis of Enamino‐ and α‐Aminophosphonates as Peptidomimetics of Analgesic/Antiinflammatory and Anticancer Agents

Abstract

Carbodiimide that was generated from the condensation reaction of iminophosphorane with phenylisocyanate was allowed to react with different phosphorus nucleophiles. Thus, the in situ resulted heterocumulene reacted with dialkylhydrogenphosphonates in tetrahydrofuran (THF)/FeCl(3) /H(2) O system to give fused pyrrole- (≈14%) and pyrimidinephosphonates (≈57%). On the other hand, with tris-(dialkyl)aminophosphines, the reaction afforded the corresponding hexaalkylphosphinic diamides as a water-sensitive fine powder, quite stable for a few days in a desiccator. When a protonating agent was present in the reaction medium, the reaction was markedly accelerated leading to the formation of the phosphamides. Next, some saturated and unsaturated Horner-Emmons reagents were applied in situ to the same carbodiimide to obtain more phosphorylated N-heterocycles. The analgesic and antiinflammatory activities of the newly synthesized compounds were investigated and showed significant activities. Finally, we further estimated the antitumor activity of five new phosphonates against four carcinoma cell lines.

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

“…Generally, cancers of the breast, lung, colon, and prostate are the most frequent types of cancer worldwide [1][2][3]. This paper along with our recent efforts focuses on developing, identifying, and optimizing new entities of anticancer properties [4][5][6][7][8][9][10].…”

Investigations of the Chemistry of Alkyl Phosphites Toward Nitrogen-Containing Compounds: Efficient Approaches to α-Amino-, β-Amino-, and/or Enaminophosphonates

“…The latter was obtained by treating o-aminonitrile 53 with triphenylphosphines to give the iminophosphorane 54, which is further trapped with isocyanate to generate 55 (Scheme 23). [75] Appling the same protocol to the amine 58, a series of N-MBPs 59a-c was obtained (Scheme 24). [76,77] Finally, when N-heterocycles 60a-d were stirred with HC(OEt) 3 and DAP (2 mol equiv), the N-BPs 61a-d were obtained.…”

One-pot three-component synthesis of peptidomimics for investigation of antibacterial and antineoplastic properties

“…In addition, these new agents may overcome tumor resistance. In sequel, and in continuation of our cancer-treatment (Abdou et al, 2012a(Abdou et al, ,b,c,d, 2013aKamel et al, 2012) and antibiotic research programs (Abdou et al, 2009a(Abdou et al, ,b, 2014bAbdou and Khidre, 2010), we have recently considered the anticancer-antibiotic relationship studies (Abdou et al, 2014a).…”