Table 2. Ki values for inhibition of human GARFTase by 6-pyrrolo[2,3-d]pyrimidine heteroatom analogs.
GARFTase activity was determined by measuring formation of 5,8-dideazafolate from 10-formyl-5,8-dideazafolic acid using a spectrophotometric assay (295 nm) in the presence of the indicated antifolate. Detailed methods are described in the Experimental Section. Results are shown as mean values +/− standard errors from three replicate assays. The results for compound 3 and PMX were previously reported.18 Abbreviation; Cpd, compound
| Antifolate | Ki (nM) |
|---|---|
| PMX | 1000 +/− 160 |
| Cpd 1 | 160 ± 17 |
| Cpd 3 | 68 +/− 11 |
| Cpd 4 | 59 ± 9 |
| Cpd 5 | 99 ± 15 |
| Cpd 6 | 62 ± 7 |
| Cpd 7 | 122 ± 14 |
| Cpd 8 | 61 ± 4 |
| Cpd 9 | 201 ± 36 |