19407-42-2Relevant articles and documents
Synthesis and antitumor evaluation of novel 5-substituted-4-hydroxy-8- nitroquinazolines as EGFR signaling-targeted inhibitors
Jin, Yi,Li, Hui-Yuan,Lin, Li-Ping,Tan, Jinzhi,Ding, Jian,Luo, Xiaomin,Long, Ya-Qiu
, p. 5613 - 5622 (2005)
The synthesis and biological activity of a series of novel 5-substituted-4-hydroxy-8-nitroquinazolines that may function as inhibitors of EGFR- and/or ErbB-2-related oncogenic signaling are described. These compounds were prepared by SNAr reaction of 5-chloro-4-hydroxy-8- nitroquinazoline with alkyl or aryl amines, or alkyl alcohol as nucleophiles. Although the enzyme assay showed a weak inhibition effect against both EGFR and ErbB-2 tyrosine kinases, the cell-based antitumor activity turned out promising. Compounds having 5-anilino substituent exhibit high potency with 5-(4-methoxy)anilino-4-hydroxy-8-nitroquinazoline (1h) being the best dual EGFR/ErbB-2 inhibitors, which effectively inhibited the growth of both EGFR (MDA-MB-468, IC50 50 = 13 μM) overexpressing human tumor cell lines in vitro. More interestingly, the variation of the substituent(s) at the 3- and/or 4-position of the 5-anilino portion was found to modulate the selectivity and potency dramatically. However, compounds having an alkylamino or alkyloxy group at the 5-position of 4-hydroxy-8-nitroquinazolines are essentially inactive. These results are consistent with molecular modeling observations. This study was the first attempt to identify new structural types of dual EGFR/ErbB-2-related signaling inhibitors by incorporation of the anilino group at the 5-position of 4-hydroxy-8-nitroquinazolines' core structure, providing promising new templates for further development of potent inhibitors targeting both EGFR and ErbB-2 tyrosine kinases.
Herbicidal substituted benzoylsulfonamides
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, (2008/06/13)
Compound of the formula STR1 in which A is O, S, or NR3 ; G is CH or N; R and R1 are independently alkyl, alkoxy, haloalkoxy or alkylamino; R2 is phenyl, substituted phenyl, alkyl, cycloalkyl, haloalkyl or --CH2 [(R4)C(R5)n --Z; R3 and R7 are, independently, hydrogen, alkyl, --C(O)NH2 or --C(O)alkyl; R4 and R5 are independently hydrogen, alkyl, or halogen; R6 is halogen, alkyl, alkoxy, haloalkoxy, NO2, amino, alkyl substituted amino, or acyl substituted amino; n is 0 to 5; Z is cyano, amino, alkylamino, dialkylamino, --NHCO2 alkyl, alkoxy, alkylthio, alkylsulfonyl, alkenyl, alkynyl, phenyl or substituted phenyl; and Q is hydrogen, halogen, alkyl, alkoxy, haloalkoxy, nitro, amino, haloalkyl, alkythio, alkylsulfonyl, phenyl, substituted phenyl or phenoxy; or a 5 or 6 membered aromatic heterocycle having the formula STR2 in which "m" is 0 or 1; A' is O, S, or NR7 ; and X, X', Y, Y', W, W', V, V', U and Z' are independently N, O, S, --CH-- or --CR6. Intermediates for preparation of the benzoylsulfonamides are also disclosed.
