Pteridines Part CXI - Pteridine-based photoaffinity probes for nitric oxide synthase and aromatic amino acid hydroxylases

Various 6-substituted pteridines and 5,6,7,8-tetrahydropterins carrying pho tolabile functions at the side chain (see 7, 20-22, 34-36, 38, and 39) as w ell as at the 5-position (see 27-29) were synthesized from pterin and from 6-phenylpterin (1) and 6-(hydroxymethyl)pterin (10). Attachment of the phot oaffinity labels via ester bonds required a special protecting-group strate gy based upon acid-labile (see 30-33) and beta -eliminating blocking groups (see 17-19). The 6-(4-azidophenyl)pterin (7) was obtained from 6-phenylpte rin (1) via intermediates 2 and 4-6, due to the low solubility of simple pt erins in general. The pteridine derivatives 21 22, 25, 26, 28, 29, 32, 33, 35, 36, 38, and 39 were screened as inhibitors of neuronal (type I) NO synt hase (see Table) from porcine cerebellum, of which 22, 35, 36, and 38 showe d interesting inhibitory activity with similar potency and effectiveness.