19990-25-1Relevant articles and documents
Derivatives of aryl amines containing the cytotoxic 1,4-dioxo-2-butenyl pharmacophore
Jha, Amitabh,Mukherjee, Chandrani,Prasad, Ashok K.,Parmar, Virinder S.,Vadaparti, Manjula,Das, Umashankar,De Clercq, Erik,Balzarini, Jan,Stables, James P.,Shrivastav, Anuraag,Sharma, Rajendra K.,Dimmock, Jonathan R.
supporting information; experimental part, p. 1510 - 1515 (2010/06/16)
Several series of compounds containing the 1,4-dioxo-2-butenyl moiety have been prepared as candidate cytotoxins, including the methyl N-arylmaleamates, methyl N-arylfumaramates, and N-arylmaleimides. In addition, the N-arylisomaleimides were synthesized which are the structural isomers of N-arylmaleimides. These compounds were evaluated against human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 cells. Methyl N-arylfumaramates showed the highest cytotoxic potencies and, in particular, methyl N-(3,4-dichlorophenyl)fumaramate is six times more potent than melphalan towards L1210 cells and is equipotent with this drug in the Molt 4/C8 assay. Electrophilicity of compounds under investigation was demonstrated by carrying out thiolation using model benzyl mercaptan on representative compounds. Methyl N-(3,4-dichlorophenyl)fumaramate and methyl N-(4-chlorophenyl)maleamate inhibited human N-myristoyltransferase, a possible molecular target, in high micromolar range. QSAR and molecular modeling revealed some correlations between different structural features of a number of the molecules and cytotoxic potencies. Methyl N-arylfumaramates were well tolerated in mice in comparison to the analogs in other series of compounds tested. The data obtained in this investigation affords guidelines for preparing new series of molecules with greater potencies.
SYNTHESIS AND SOME REACTIONS OF N-ARYLMALEISOIMIDIUM PERCHLORATES
Ismail, Mohamed Fekry,Enayat, Ebtesam Ismail,Bassiouny, Fakhry Abdel Aziz El,Younis, Hamed Ahmed
, p. 365 - 373 (2007/10/02)
N-Arylmaleisoimidium perchlorates (1a and b) were prepared by the action of acetic anhydride and perchlorid acid on the N-arylmaleamic acids (2a and b).Compound 1b reacted with amines via ring-opening to give N,N-disubstituted maleamides (4a-c), while the reaction of 1a with secondary amines gave N-phenylmaleimide (6).The reaction of 1a and b with aromatic hydrocarbons in the presence of anhydrous aluminium chloride gave good yields of trans-β-aroyl-N-arylacrylamides (7a-h).The reactions of some of the latter compounds with amines and phenylhydrazine are also discussed.
