Chromatography over silica gel, eluting with ethyl acetate :hexanes afforded Step 2: 5-Acetylaminobromoindane To a solution of 5-acetylaminoindane Step 3: 5 -Acetylaminobromo- 1 -indanone To a solution of 5-acetylaminobromoindane Solvent was removed in vacuo.
The residue was diluted with water 1 L and extracted with ethyl acetate 2 x mL. The combined ethyl acetate layer was washed with 0. Step 4: 5- Aminobromo- 1 -indanone A mixture of 5-acetylaminobromo-l -indanone The precipitate formed was collected, washed with water and dried under vacuum to afford Step 5: 5 -Nitrobromo-l -indanone To a suspension of 5 -aminobromo-l -indanone The mixture was stirred for 30 min after completion of addition. The resulting foamy suspension was added portionwise to a vigorously stirred mixture of copper powder 40 g, 0.
During the addition, excessive foaming was broken up by the addition of small amounts of diethyl ether. After further stirring for 30 min, the mixture was filtered through celite, washed with ethyl acetate 5 x mL. The ethyl acetate layer was separated, washed with brine, dried over anhydrous MgS04 and concentrated in vacuo. Chromatography over silica gel, eluting with CH2CI2, yielded Step 6: 5-Nitrobromo-l -indanone ethylene ketal To a suspension of 5-nitrobromo-l -indanone Chromatography over silica gel, eluting with ethyl acetate :hexanes , furnished Klages and K.
This indicates that a methoxy group at this position is preferred for the activity. Comparatively, electron-withdrawing substituted compounds exhibited very weak or no activity. This suggests that mono- or di-substitution of electron-withdrawing functional groups on benzene ring B is not tolerated.
Optimization at the benzene ring A of 1-indanone to obtain 8f To further improve the anti-inflammatory activity and, in particular, inhibition on IL-6, we next directed our optimization effort to modify the benzene ring A of 4d by introducing different types of groups. These results are shown in Table 2. Incorporation of hydroxyl group at the 7- and 5-position of benzene ring A led to compounds 8a and 8b, which, respectively, showed either markedly reduced or no activity.
Meanwhile, etherification at the 4-, 5-, 6-, or 7-hydroxyl group with O-propyl or O-isopropyl moieties produced compounds 8g-8n.
This result indicates that the three-carbon chain alkoxy groups at the C-7 position for 8g and 8k were beneficial to the activity. Further screening of substituents around 4d revealed that incorporation of various substituted amino groups at the o-position on the phenyl ring provided compounds 8o-8s. Except for 8s, which has an acetylamino group on the benzene ring, these compounds exhibited a significantly decreased anti-inflammatory ability Illustration of the structure—activity relationship of these 2-benzylideneindanone derivatives is presented in Figure 2.
Figure 2 Structure—activity relationships of 2-benzylideneindanone derivatives. As shown in Table 2 , all of these compounds showed no significant toxicity in hepatic cells, indicating that they are relatively safe. MPMs were pretreated with compounds in a series of concentrations 1. Authors contributing to RSC publications journal articles, books or book chapters do not need to formally request permission to reproduce material contained in this article provided that the correct acknowledgement is given with the reproduced material.
If the material has been adapted instead of reproduced from the original RSC publication "Reproduced from" can be substituted with "Adapted from".
In all cases the Ref. To improve the inhibition of IL-6, we further performed a lead optimization program to modify the A ring of the 4d to yield 19 new 2-benzylideneindanone derivatives. Preliminary structure—activity relationship SAR analyses were performed to outline the relationships between structures and their pharmacological activity. The active compound 8f showed improved anti-inflammatory activities in vitro and significant therapeutic effects in a mouse model, suggesting the potential of 2-benzylideneindanone derivatives for the development of new anti-inflammatory agent for the treatment of ALI.The sum of all scores was combined to calculate a composite score, as described previously. F The cell lysate level of the cytokine IL The ethyl acetate extract was washed successively with 1 M aqueous NaOH 2x ,0. These low provide evidence for the anti-inflammatory near of 2-benzylideneindanones 4d, 8f, and 8g, which primarily affect the cytokine profile at the mRNA particulate. The mixture was cast for 15 min. Terre'Blanche and M.
The mixture was stirred for 30 min. After further stirring for 30 min, the mixture was filtered through celite, washed with ethyl acetate 5 x mL. The solid residue was suspended in ethanol and filtered to give the title compound. Authors contributing to RSC publications journal articles, books or book chapters do not need to formally request permission to reproduce material contained in this article provided that the correct acknowledgement is given with the reproduced material. Thus, it may be used in the preparation of key intermediates for several drugs and natural products.
The solid residue was suspended in ethanol and filtered to give the title compound. P-values less than 0. Disclosure The authors report no conflicts of interest in this work.
Step 5: 5 -Nitrobromo-l -indanone To a suspension of 5 -aminobromo-l -indanone If you are the author of this article you do not need to formally request permission to reproduce figures, diagrams etc. At the end of the experiment, animals were sacrificed at 6 h after LPS challenge. During the addition, excessive foaming was broken up by the addition of small amounts of diethyl ether. The mixture was stirred at room temperature for 1 h and then acidified with 1M aqueous hydrochloric acid. The ethyl acetate layer was separated, washed with water, brine, dried over anhydrous magnesium sulfate and concentrated.