Simple pyrrolidinyl and piperdinyl amide derivatives 29 have been prepared using a solid phase combinatorial library approach and show affinity for UT (58, 59). Two broad sub-series of compounds are evident that differ by either the presence or absence of an amino acid moiety bridging the pyrrolidine ring and a terminal amide group. Additionally, replacement of the alkyl group linking the (substituted)phenyl moiety to the pyrrolidinyl ring with a sulfonamide group as in 30 - 33 is clearly tolerated in the series (60 - 63) based on more recent disclosures but the presence of an alternate basic center elsewhere in the molecule appears to be necessary.
Remarkably, UT activity is insensitive to considerable structural change in the series as evidenced by the introduction of relatively large groups on the periphery of the molecule (29) or change of the core from a 5-membered pyrrolidine (30) to a 6-
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