8-Substituted analogues of 3-(3-cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl-adenine: highly potent and selective PDE4 inhibitors.
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Whitehead JW, Lee GP, Gharagozloo P, Hofer P, Gehrig A, Wintergerst P, Smyth D, McCoull W, Hachicha M, Patel A, Kyle DJ
8-Substituted analogues of 3-(3-cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl-adenine: highly potent and selective PDE4 inhibitors.
J Med Chem. 2005 Feb 24;48(4):1237-43.
- PubMed ID
- 15715490 [ View in PubMed]
- Abstract
3-(3-Cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl-adenine V11294 (1) has been identified as a lead structure, which selectively inhibits human lung PDE4 (436 nM) and is also active in a number of in vitro and in vivo models of inflammation. Here we describe the synthesis and pharmacology of a series of highly potent 8-[(benzyloxy)methyl]-substituted analogues, with potencies in the range 10-300 nM. In addition, several compounds showed interesting PDE4 subtype specificities, for example, the 3-thienyl derivative 5v, which showed 6-10 nM potency at PDE4B, D3, and D5 and a 20- to 200-fold selectivity over A and D2, respectively.
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- Binding Properties
Drug Target Property Measurement pH Temperature (°C) (R)-Rolipram cAMP-specific 3',5'-cyclic phosphodiesterase 4B Ki (nM) 1470 8 22 Details