Nitrogen analogs of 1,4-benzoquinones. Activities against the ascitic sarcoma 180 of mice

Abstract

Compounds having the basic structure N-(R)-substituted ring-substituted 4-iminocyclohexadienone have been synthesized and tested as antitumor agents against the ascitic sarcoma 180 tumor in Swiss mice. Among these compounds, the dimethylindoanilines [R = 4-(CH3)2NC6H4] are most stable in water at pH 7.0 and at 25 degrees C, the oximes (R = oh) are less stable, and the N-halo compounds (R = Br and Cl) are least stable. The N-halo derivatives have the highest redox potentials under the conditions used, the greatest effect against ascitic sarcoma 180 in Swiss mice, and the greatest acute toxicity when injected ip in the Swiss mice. Discriminant analysis of the results indicates that substituents with positive values of F and negative values of pi increase the antitumor activities, whereas those with positive values of sigma and R should lower the toxicity. The redox potential, a molecular parameter, is the best single variable for discriminating between the groups based on antitumor activities.

Syntheses and Characterization of the Acyl Glucuronide and Hydroxy Metabolites of Diclofenac

“…This compound has been made from the expensive 3,5dichlorophenol in four steps and 12% overall yield 13,15 or by the very low-yielding chlorination of 4-methoxyaniline. 16 We made use of a reported 17,18 two-step synthesis from phenol 6 commencing with nitrosation, 19 which afforded benzoquinone monoxime 7 in 77% yield.…”

“…This compound was prepared according to a literature procedure 19 on a 0.1 M scale; yield, 9.47 g (77%); mp 139-141 °C (lit. 19 mp 137-138 °C). 1 H NMR (250 MHz, CDCl3): δ 6.52 (2 H, dd, J ) 10.4 and 2.0 Hz, H-2 + H-6), 7.22 (1 H, dd, J ) 10.5 and 2.8 Hz, H-5), 7.77 (1 H, dd, J ) 10.8 and 2.2 Hz, H-3), and 8.86 (1 H, br s, OH).…”

“…This compound has been made from the expensive 3,5-dichlorophenol in four steps and 12% overall yield , or by the very low-yielding chlorination of 4-methoxyaniline . We made use of a reported , two-step synthesis from phenol 6 commencing with nitrosation, which afforded benzoquinone monoxime 7 in 77% yield. Our initial attempts to convert 7 into 5 by reaction with gaseous HCl in dioxan−methanol or methanol−ether afforded mainly 2-chloro-4,6-dimethoxyaniline 8 , noted as a byproduct by Goldschmidt .…”

Synthesis and characterisation of some 4-keto derivatives of 1,3,4(2H)-isoquinolinetrione redox mediator herbicides

“…It is known that derivatives of carbonyl compounds, eg oximes and hydrazones, are more stable towards nucleophilic attack than the parent carbonyl compound,4 and that quinones in which one of the carbonyl groups has been chemically modified, eg substituted imino functions and dicyanomethylene derivatives, can maintain an ability to enter into redox reactions 5–7. Since the hydrolysis of 1,3,4( 2H )‐isoquinolinetriones proceeds via an initial nucleophilic attack at the 4‐keto function,1, 8 we reasoned that derivatives bearing modified 4‐keto groups might be of interest as new redox mediator herbicides, since they might combine favourable electrochemical properties with enhanced hydrolytic stability relative to the parent ketone.…”

Quantitative Structure-Activity Relationship Studies on Anticancer Drugs

“…Although this correlation is not very significant, it suggests that the reduction potential of nitro group would be an important factor in radiosensitizing potency of the compounds. In a study on nitroimidazoles (XXXVII and XXXVIII) XXXVII XXXVIII against hypoxic bacterial cells (Escherichia coli and S. lactis), it was shown30 that this potential along n = 9, r = 0.97, s = 0.16 (81) log(l/C17) = 9.53(±2.47)E'1 + 1.49(±0.12) logP + 6.74(±0.97)…”