Design and synthesis of some TSA inhibitors on novel molecular frameworks is described. This TSA analog design culminates in the preparation of the phosphonate 18.

A series of substrate analog inhibitors of 14 kDa PLA2 possessing replacements for the sn-3 phosphate moeity was prepared and evaluated. Tetrazole 26 possessed similar in vitro inhibition potency to phosphate-containing substrate analog inhibitors, but demonstrated superior cell permeability as monitored by LTC4 release in monocytes.