| Title : Novel isoindoline compounds for potent and selective inhibition of prolyl dipeptidase DPP8 - Jiaang_2005_Bioorg.Med.Chem.Lett_15_687 |
| Author(s) : Jiaang WT , Chen YS , Hsu T , Wu SH , Chien CH , Chang CN , Chang SP , Lee SJ , Chen X |
| Ref : Bioorganic & Medicinal Chemistry Lett , 15 :687 , 2005 |
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Abstract :
DPP8 is a prolyl dipeptidase homologous to DPP-IV, which is a drug target for Type II diabetes. The biological function of DPP8 is not known. To identify potent and selective chemical compounds against DPP8, we have synthesized a series of isoquinoline and isoindoline derivatives and have tested their inhibitory activity against DPP8, DPP-IV and DPP-II. Isoindoline derivatives were found to be more potent DPP8 inhibitors than isoquinoline derivatives. Isoindoline with a 1-(4,4'-difluor-benzhydryl)-piperazine group at the P2 site was observed to be a very potent DPP8 inhibitor, having an IC(50) value of 14nM with at least a 2500-fold selectivity over either DPP-IV or DPP-II. From SAR results, we speculate that the S1 site of DPP8 may be larger than that of DPP-IV, which would allow the accommodation of larger C-terminal residues, such as isoquinoline or isoindoline. |
| PubMedSearch : Jiaang_2005_Bioorg.Med.Chem.Lett_15_687 |
| PubMedID: 15664838 |
| Gene_locus related to this paper: human-DPP8 |
| Inhibitor | isoquinolinederivative18 |
| Gene_locus | human-DPP8 |
Jiaang WT, Chen YS, Hsu T, Wu SH, Chien CH, Chang CN, Chang SP, Lee SJ, Chen X (2005)
Novel isoindoline compounds for potent and selective inhibition of prolyl dipeptidase DPP8
Bioorganic & Medicinal Chemistry Lett
15 :687
Jiaang WT, Chen YS, Hsu T, Wu SH, Chien CH, Chang CN, Chang SP, Lee SJ, Chen X (2005)
Bioorganic & Medicinal Chemistry Lett
15 :687