國家衛生研究院 NHRI:Item 3990099045/1231

NHRI > Institute of Biotechnology and Pharmaceutical Research > Xin Chen(2002-2015) > Periodical Articles > Item 3990099045/1231

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/1231

Title:	Novel isoindoline compounds for potent and selective inhibition of prolyl dipeptidase DPP8
Authors:	Jiaang, WT;Chen, YS;Hsu, T;Wu, SH;Chien, CH;Chang, CN;Chang, SP;Lee, SJ;Chen, X
Contributors:	Division of Biotechnology and Pharmaceutical Research
Abstract:	DPP8 is a prolyl dipeptidase homologous to DPP-IV, which is a drug target for Type 11 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 IC50 value of 14nM with at least a 2500-fold selectivity over either DPP-IV or DPP-II. From SAR results, we speculate that the S I site of DPP8 may be larger than that of DPPIV, which would allow the accommodation of larger C-terminal residues, such as isoquinoline or isoindoline.
Keywords:	Chemistry, Medicinal;Chemistry, Organic
Date:	2005-02-01
Relation:	Bioorganic and Medicinal Chemistry Letters. 2005 Feb;15(3):687-691.
Link to:	http://dx.doi.org/10.1016/j.bmcl.2004.11.023
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0960-894X&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000226935700039
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=12444313913
Appears in Collections:	[Xin Chen(2002-2015)] Periodical Articles [Shiow-Ju Lee] Periodical Articles [Weir-Torn Jiaang] Periodical Articles

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