Table 1.
SAR studies on the selective COX-2 inhibition by indomethacin amides and esters
| Compound | R | IC50*
|
IC50 (COX-1)/ IC50 (COX-2)† | |
|---|---|---|---|---|
| oCOX-1 | hCOX-2 | |||
| Indomethacin | OH | 0.050 | 0.75 | 0.070 |
| 4 | HNCH3 | >66 | 0.70 | >90 |
| 5 | OCH3 | 33 | 0.25 | 130 |
| 6 | HN(CH2)2OH | >66 | 0.25 | >287 |
| 7 | HNC6H5(4-NHCOCH3) | >66 | 0.12 | >600 |
| 8 | OC6H5(4-OCH3) | >66 | 0.040 | >1,700 |
| 9 | OC6H5(4-SCH3) | 2.6 | 0.30 | 8.7 |
| 10 | OC6H5(2-SCH3) | >66 | 0.060 | >1,100 |
| 11 | OC6H5(4-F) | 3.0 | 0.075 | 40 |
| 12 | O(3-C5H4N) | 2.5 | 0.050 | 50 |
| 13 | HNC6H5(4-SCH3) | >66 | 0.12 | >600 |
| 14 | HNC6H5(4-F) | >66 | 0.060 | >1,100 |
| 15 | HN(3-C5H4N) | >66 | 0.050 | >1,300 |
| 16 | NC5H10 | >66 | >16.5 | — |
| 17 | N(CH3)(CH2)2C6H5 | >66 | >16.5 | — |
| 18 | NH2 | >20 | 0.70 | >29 |
| 19 | HN(CH2)2C6H5 | >66 | 0.060 | >1,100 |
| 20 | O(CH2)2C6H5 | >66 | 0.050 | >1,320 |
| 21 | ‡ | >66 | >66 | — |
| 22 | ‡ | >66 | >66 | — |
| 23 | ‡ | >66 | 2.5 | >26 |
*
IC50 values in μM represent time-dependent COX inhibition and are average values from duplicate experiments.
†COX-2 selectivity ratio.
‡ Contains p-bromobenzyl group on the indole nitrogen. The R group in compounds 21, 22, and 23 are phenethyl amide, phenethyl ester, and free acid, respectively.