Phenylphthalimides with tumor necrosis factor alpha production-enhancing activity.
Y Shibata, K Sasaki, Y Hashimoto, S Iwasaki
文献索引:Chem. Pharm. Bull. 44(1) , 156-62, (1996)
全文:HTML全文
摘要
Phenylphthalimides (2-phenyl-1H-isoindole-1,3-diones) were prepared and their effects on tumor necrosis factor alpha (TNF-alpha) production by human leukemia cell line HL-60 stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA) were examined. An analysis of the structure-activity relationships of the phenylphthalimides indicated that potent enhancing activity on TPA-induced TNF-alpha production by HL-60 cells requires medium-sized substituent(s) at the ortho position(s) of the phenyl group; 2-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (PP-33) increased the TNF-alpha production to more than 600% at the concentration of 1 x 10(-5) M. Introduction of a nitro group at the phthalimide moiety of PP-33 enhanced the activity; 2-(2,6-diisopropylphenyl)-4-nitro-1H-isoindole-1,3-dione (4NPP-33) and its 5-nitro isomer (5NPP-33) enhanced the TNF-alpha production to more than 800% and 700%, respectively, at the concentration of 1 x 10(-5) M. Introduction of fluorines into the phthalimide moiety of PP-33 greatly lowered the concentration of the compound necessary to elicit the TNF-alpha production-enhancing activity; 2-(2,6-diisopropylphenyl)-4,5,6,7-tetrafluoro-1H-isoindole-1,3-dio ne (FPP-33) showed the activity at nanomolar concentration, with the optimum concentration of 1 x 10(-7) M.
相关化合物
相关文献:
2011-08-11
[J. Med. Chem. 54 , 5454, (2011)]
1999-02-22
[Bioorg. Med. Chem. Lett. 9(4) , 559-62, (1999)]
2004-08-01
[Chem. Pharm. Bull. 52(8) , 1021-2, (2004)]
2010-07-15
[Bioorg. Med. Chem. 18(14) , 5323-38, (2010)]
2009-09-01
[Biol. Pharm. Bull. 32(9) , 1618-20, (2009)]