21395-61-9Relevant 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.
scheme or table, 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.
GHRELIN RECEPTOR MODULATORS
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Page/Page column 39, (2008/12/07)
Compounds of Formula (IA) or (IB) modulate ghrelin receptor activity, and are useful in the treatment of, for example, obesity and eating disorders: wherein W is, in either orientation, -C(=O)N(R3)-, or -C(=O)O-; R is hydrogen or C1-C4 alkyl; R1 is selected from hydrogen, (C1-C4)alkyl, cycloalkyl, fully or partially fluorinated (C1-C4)alkyl, or -OR10; and R2 is selected from (i) hydrogen and (ii) (C1-C4)alkyl, cycloalkyl, cycloalkenyl, and non aromatic heterocyclyl, each optionally substituted by -F, -CN, C1-C4 alkyl, cyclopropyl, -NR7COR0, -NR7SO2R0, -COR0, -COOH, -SOR9, -SO2R0, -OR10, -NR7R8, or -NR7COOR8; and (iii) aryl, aryl-(C1-C2)alkyl-, heteroaryl and heteroaryl-(C1-C2 alkyl)- each optionally substituted in the ring part or R1 and R2, together with the nitrogen to which they are attached, form an optionally substituted cyclic amino group; R3 is selected from hydrogen, (C1-C4)alkyl, cycloalkyl, fully or partially fluorinated (C1-C4)aIkyl, or -OR10; and R4 is selected from (iv) hydrogen and (v) (C1-C4)alkyl, cycloalkyl, and non aromatic heterocyclyl, each optionally substituted by -F, -CN, -NR7COR0, -NR7SO2R0, -COR0, - COOH, -SOR9, -SO2R0, -OR10, -NR7R8, or -NR7COOR8; and (vi) aryl, aryl-(C1-C2)alkyl-, heteroaryl and heteroaryl-(C1-C2 alkyl)- each optionally substituted in the ring part thereof; or R3 and R4, together with the nitrogen to which they are attached, form an optionally substituted cyclic amino group; L is a linker radical of formula -(CR11R13)aB(CR12R14)b- as defined in the specification; R0, R7, R8, R9 and R10 are as defined in the specification.
Syntheses of 4-(3,5-bisphenylmethylene-4-oxopiperidin-1-yl)-4-oxo-but-2Z-enoic acid arylamides as candidate cytotoxic agents
Jha, Amitabh,Dimmock, Jonathan R.
, p. 1211 - 1223 (2007/10/03)
The title compounds were designed and synthesized as candidate cytotoxic agents. They were synthesized by reacting 3,5-bisphenylmethylene-piperidin-4-one with the appropriate 3-arylcarbamoylacrylic acids. These reactions follow an unusual mechanism and deviate from the previously reported reactions on similar substrates.
