56525-67-8Relevant academic research and scientific papers
Synthesis and quantitative structure-activity relationship of imidazotetrazine prodrugs with activity independent of O6-methylguanine-DNA- methyltransferase, DNA mismatch repair, and p53
Pletsas, Dimitrios,Garelnabi, Elrashied A.E.,Li, Li,Phillips, Roger M.,Wheelhouse, Richard T.
, p. 7120 - 7132 (2013/10/01)
The antitumor prodrug temozolomide is compromised by its dependence for activity on DNA mismatch repair (MMR) and the repair of the chemosensitive DNA lesion, O6-methylguanine (O6-MeG), by O6-methylguanine-DNA-methyltransferase (E.C. 2.1.1.63, MGMT). Tumor response is also dependent on wild-type p53. Novel 3-(2-anilinoethyl)-substituted imidazotetrazines are reported that have activity independent of MGMT, MMR, and p53. This is achieved through a switch of mechanism so that bioactivity derives from imidazotetrazine-generated arylaziridinium ions that principally modify guanine-N7 sites on DNA. Mono- and bifunctional analogues are reported, and a quantitative structure-activity relationship (QSAR) study identified the p-tolyl-substituted bifunctional congener as optimized for potency, MGMT-independence, and MMR-independence. NCI60 data show the tumor cell response is distinct from other imidazotetrazines and DNA-guanine-N7 active agents such as nitrogen mustards and cisplatin. The new imidazotetrazine compounds are promising agents for further development, and their improved in vitro activity validates the principles on which they were designed.
Solvent-promoted and -controlled Aza-Michael reaction with aromatic amines
De, Kavita,Legros, Julien,Crousse, Benoit,Bonnet-Delpon, Daniele
experimental part, p. 6260 - 6265 (2009/12/06)
(Chemical Equation Presented) 1,4-Addition of anilines onto Michael acceptors proceeds easily in specific polar protic solvents, without any promoting agent. According to the solvent and to the electrophile, the selectivity of the reaction can be finely tuned. With methyl acrylate as electrophile, only monoaddition takes place in water, while the diadduct is yielded in hexafluoroisopropyl alcohol (HFIP). The use of methyl vinyl ketone as a partner affords the monoadduct in water, the diadduct in trifluoroethanol (TFE), and the quinoline in HFIP.
An efficient ZrCl4 catalyzed aza-michael addition reaction: Synthesis of C-linked carbo β3-amino acids
Damera, Krishna,Reddy, Katta L.,Sharma, Gangavaram V.M.
experimental part, p. 151 - 155 (2010/04/23)
A mild aza-Michael protocol has been developed using ZrCl4 as catalyst on α, β-unsaturated esters and nitriles. The aromatic amines were found to give the products with ease. The ZrCl4 mediated route was compatible with acid sensitive carbohydrate esters and provided an efficient method to prepare C-linked carbo β3-amino acids (β3-Caa).
