77189-70-9Relevant academic research and scientific papers
Antimitotic antitumor agents: Synthesis, structure-activity relationships, and biological characterization of N-aryl-N′-(2-chloroethyl)ureas as new selective alkylating agents
Mounetou,Legault,Lacroix,C-Gaudreault
, p. 694 - 702 (2001)
A series of N-aryl-N′-(2-chloroethyl)ureas (CEUs) and derivatives were synthesized and evaluated for antiproliferative activity against a wide panel of tumor cell lines. Systematic structure-activity relationship (SAR) studies indicated that: (i) a branched alkyl chain or a halogen at the 4-position of the phenyl ring or a fluorenyl/indanyl group, (ii) an exocyclic urea function, and (iii) a N′-2-chloroethyl moiety were required to ensure significant cytotoxicity. Biological experiments, such as immunofluorescence microscopy, confirmed that these promising compounds alter the cytoskeleton by inducing microtubule depolymerization via selective alkylation of β-tubulin. Subsequent evaluations demonstrated that potent CEUs were weak alkylators, were non-DNA-damaging agents, and did not interact with the thiol function of either glutathione or glutathione reductase. Therefore, CEUs are part of a new class of antimitotic agents. Finally, among the series of CEUs evaluated, compounds 12, 15, 16, and 27 were selected for further in vivo trials.
Reactions of o-Aminonitriles with Isocyanates. 1. A Two-Step Synthesis of 2,6-Dihydroimidazoquinazolin-5-(3H)one
Papadopoulos, Eleftherios Paul
, p. 1553 - 1558 (2007/10/02)
The reaction of anthranilonitrile with 2-chloroethyl isocyanate yields 2-benzonitrile (6) which, upon heating, or treatment with base, undergoes a double cyclization to form 2,6-dihydroimidazoquinazolin-5-(3H)one (8) in excellent yield.When heated with hydrochloric acid, 6 is converted initially into 2-(2-chloroethylamino)-4H-benzoxazin-4-one (18) and further into 3-(2-chloroethyl)-2,4-(1H,3H)quinazolinedione (15).The acid-catalyzed reaction of 2,3-dihydro-5H-oxazoloquinazolin-5-one (14) with nucleophilic reagents yields 3-substituted 2,4-(1H,3H)quinazolinediones.
