New simplified inhibitors of EPSP synthase: The importance of ring size for recognition at the shikimate 3-phosphate site

The simple 4-[(α-hydroxy)phosphonomethyl]-1H-pyrrole-2-carboxylate 4 is a surprisingly good S3P-analog inhibitor of EPSP synthase (competitive with S3P, Ki(app) = 14.5 ± 0.7 μM). The affinity of 4 for free enzyme is nearly comparable to that of S3P (Kd = 7 ± 1.2 μM). Compound 4 thus represents the first successful attempt to replace the highly substituted shikimate ring in S3P with a readily accessible heterocyclic scaffold.