2-(Arylsulfonyl)indane-1,3-diones, earlier synthesized by Claisen condensation involving diethyl phthalate and aryl methyl sulphones, are found to be potent blood anticoagulants. In search of improved analogs of 2-(arylsulfonyl)indane-1,3-dione, we have synthesized them
Indane-1,3-dione and its derivatives constitute a unique group of compounds and attracted the attention of organic chemists and biologist due to their three characteristic features [
A survey of literature revealed that derivatives of indane-1,3-dione particularly 2-arylsulfonylindane-1,3-diones have been found to be potent blood anticoagulants [
In an attempt to prepare improved analogs of 2-(arylsulfonyl)indane-1,3-diones, we have attempted the condensation of arylsulfonylacetic acids with phthalic anhydride under different conditions. Although, the reaction failed with arylsulfonylacetic acids, the corresponding arylsulfonylacetates readily reacted with phthalic anhydride in the presence of pyridine-piperidine medium gave phthalyl arylsulfonylacetates
The structures of the synthesized compounds
The 1H NMR spectra of
The antimicrobial activity of compounds was determined by the disc diffusion method and minimum inhibitory concentrations (MICs). Minimum inhibitory concentration is the lowest concentration of an antimicrobial agent that inhibits more than 99% of the bacterial population. MICs were determined by the macrodilution broth method following the procedures recommended by the National Committee for Clinical Laboratory Standards for testing purposes [
Antibacterial activity of compounds
Compound | Antibacterial activity | |
(zone of inhibition in mm) at 10 | ||
11 | 6 | |
13 | 5 | |
16 | 7 | |
15 | 6 | |
15 | 5 | |
14 | 6 | |
Compounds
Minimum inhibitory concentrations (MICs in
Compounds | ||
---|---|---|
9 | 8 | |
9 | 6 | |
7 | 8 | |
7 | 6 | |
7 | 8 | |
8 | 6 | |
5 | 4 |
Anticoagulant activity of compounds
Anticoagulant activity of compounds
Compound | Clotting time (min) |
---|---|
7a | 60 |
7b | 70 |
7c | 65 |
7d | 75 |
7e | 65 |
7f | 75 |
Compounds
A scrutiny of the results of antibacterial activity of
An analysis of the results of anticoagulant activity of
These contrasting results emphasize that bulky groups lower the activity of the compound by preventing it from fitting properly into the binding site of the receptor. On the other hand, bulky substituents may also increase the activity by forcing a compound to adopt the required active conformation at the binding site.
Melting points were determined on a sulphuric acid bath and are uncorrected. IR spectra were recorded on JASCO 470 FT-IR spectrometer, and 1H-NMR spectra were recorded on a 300 MHz on Bruker (Avance) NMR spectrometer using TMS as an internal standard.
To an alkaline solution of thiophenol (0.10 mol in 15% NaOH), ethyl chloroacetate (0.10 mol) was added while stirring and keeping the temperature at 0°C for about 0.5 h. The resulting oily liquid was extracted with chloroform, and the chloroform layer was washed with water and dried. Evaporation of solvent gave ethyl arylmercaptoacetate, which on oxidation with
A mixture of ethyl arylsulfonylacetate
M.p. 185°C (benzene), yield: 40%. IR (KBr): 1664 (CO), 1336 (S=O unsym. str.), 1141 (S=O sym. str.) cm−1. 1H NMR (CDCl3):
M.p. 160°C (benzene), yield 45%. IR (KBr): 1672 (CO), 1338 (S=O unsym. str.), 1138 (S=O sym. str.) cm−1. 1H NMR (CDCl3):
M.p. 153°C (pet. ether-benzene), yield 43%; IR (KBr): 1668 (CO), 1335 (S=O unsym. str.), 1129 (S=O sym. str.) cm−1. 1H NMR (CDCl3):
M.p. 145°C (pet. ether-chloroform), yield 40%. IR (KBr): 1656 (CO), 1346 (S=O unsym. str.), 1136 (S=O sym. str.) cm−1. 1H NMR (CDCl3):
M.p. 131°C (pet. ether-chloroform), yield 42%. IR (KBr): 1666 (CO), 1333 (S=O unsym. str.), 1125 (S=O sym. str.) cm−1; 1H NMR (CDCl3):
M.p. 142°C (aq. ethanol), yield 41%. IR (KBr): 1662 (CO), 1328 (S=O unsym. str.), 1119 (S=O sym. str.) cm−1. 1H NMR (CDCl3):
The authors thank School of Chemistry for providing FT-NMR (under DST-IRHPA programme) data, and one of the authors (M. J.) is grateful to Madurai Kamaraj University for USR fellowship. The authors also thank K. M. College of Pharmacy, Madurai for carrying out biological studies.