| Abstract
| - 3-(3-Cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl-adenine V11294 (1) has been identified asa lead structure, which selectively inhibits human lung PDE4 (436 nM) and is also active in anumber of in vitro and in vivo models of inflammation. Here we describe the synthesis andpharmacology of a series of highly potent 8-[(benzyloxy)methyl]-substituted analogues, withpotencies in the range 10−300 nM. In addition, several compounds showed interesting PDE4subtype specificities, for example, the 3-thienyl derivative 5v, which showed 6−10 nM potencyat PDE4B, D3, and D5 and a 20- to 200-fold selectivity over A and D2, respectively.
|
