Über Naphthyl‐essigsäuren. 3. Abhandlung: 1‐Nitronaphthyl‐2‐brenztraubensäure und 1‐Nitronaphthyl‐2‐essigsäure

Abstract

1239 l2S. Fritz M a y e r und Trudi O p p e n h e i m e r : dber Naphthyl-essigslluren. 3 . Abhandlung'): l-Nitronaphthyl-2-brenxtraubenskure und 1-Nitronaphthyl-2-essigsaure. [Aus dem Chem. Laboratorium der Universitit (Institut d. Physikal. Vereins) zu Frankfurt a. M.] (Eingegangen am 26. M&rc 1918.) Bereits in der 1. Abhandlung haben wir die Darstellung der 1-Nitronaphthyl-2-brenztraubensaure (I.) uad der l-Nitronaphthyl-2essigsaure (11.) aus dem P-Methyl-naphthalin beschrieben. Wir haben nun die beiden Sauren nach verschiedenen Richtungen hin &her untersucht. Lieferte die Oxydation der Nitronaphthyl-brenztraubensaure mit Wasserstoffsuperoxyd, wie gezeigt, die Nitronaphthyl-essigsaure, so haben wir andererseits, genao wie R e i B e r t z , in der Phenylreihe, durch Einwirkung von Kaliumpermanganat in geringer Ausbeute den 1 -N i t r o -2 -n a p h t h a l d e h y d (111.) fassen kiinnen, wPhrend daneben die 1 -N i t r o -2 -n a p h t h o e s a u r e (IV.) entstand.

Synthesis, in vitro and in vivo biological evaluation of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones as new potent anticancer agents

“…24,H 2.93,N 14.79. Found C 60.56,H 2.89,imidazo [2,1-b]thiazol-5-yl)methylene) -1,3-dihydro-2H-benzo[g]indol-2one (14). Red solid; 77% yield; mp >310 °C.…”

“…The indolinones 2a, 2k and 2q are commercially available, the other oxindoles and aldehydes were prepared according to the literature [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] (15, 18, 29 and 37), the 5-concentration test was repeated, and no significant differences were found between the two assays.…”

“…The 2-aminothiazole (54d), 2-amino-5-methylthiazole (54e), the oxindoles 2a, 2k and 2q are commercially available. The following compounds were prepared according to the literature: 53 [22], 55 [23], 1a-b [21], 2b [6], 2c [7], 2d [8], 2e [9], 2f [8], 2g [10], 2h [11], 2i [12], 2j [13], 2l [14], 2m [15], 2n [16], 2o [17], 2p [18], 2r [19], and 2s [20]. 31 31 4.1.1.…”

“…We examined the ability of the compounds to induce apoptosis at different treatment times and concentrations, using two cell lines, HeLa and A549. In HeLa cells(Figure 4, panels A and B) all three compounds(14,25 and 42) induced apoptosis in a time-and concentration-dependent manner. In this cell line we used three different concentrations (250, 500 and 1000 nM), and, even at the lowest concentration, it is clear that compound 25 is the most active of the three compounds.We examined much lower compound concentrations with A549 cells(Figure 5, panels A and B)(12.5-100 nM).…”

“…The introduction of another imidazothiazole nucleus at the 6 position of the imidazothiazole nucleus did not lead to particular advantages, and resulted detrimental for the activity if the primary imidazothiazole bears also a methyl group at position 2 (compounds 43-52), in fact none of these derivatives reached the five-concentration assay. Better results were obtained if the biimidazothiazole is condensed with 6-chloro-2-indolinone (compound 41, mean GI50 2.11 µM) or, even better, with 6,7-benzoindolinone, indeed compound 42 showed good antiproliferative activity, especially against leukemia (mean GI50=0.15 µM), colon (mean GI50=0.17 µM) and breast (mean GI50=0.16 µM) cancer cell lines.Comparing the series of 3-pyridyl(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) and4-pyridyl (15-25) derivatives, better results were obtained with the 4-pyridyl derivatives, in fact a larger number of compounds progressed to the fiveconcentration assay. Indeed, the only 3-pyridyl derivative active in the NCI 60 cell One-Dose Screen was compound 14 which resulted very active (mean GI50=1.02 µM) and derives from the 6,7benzoindolinone.…”