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http://ir.nhri.org.tw/handle/3990099045/1248
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| Title: | 2-[3-[2-[(2S)-2-cyano-1-pyrrolidinyl]-2-oxoethylamino]-3-methyl-1-oxobutyl]-1,2,3,4-tetrahydroisoquinoline: A potent, selective, and orally bioavailable dipeptide-derived inhibitor of dipeptidyl peptidase IV |
| Authors: | Tsu, H;Chen, X;Chen, CT;Lee, SJ;Chang, CN;Kao, KH;Coumar, MS;Yeh, YT;Chien, CH;Wang, HS;Lin, KT;Chang, YY;Wu, SH;Chen, YS;Lu, IL;Wu, SY;Tsai, TY;Chen, WC;Hsieh, HP;Chao, YS;Jiaang, WT |
| Contributors: | Division of Biotechnology and Pharmaceutical Research |
| Abstract: | Dipeptidyl peptidase IV (DPP-IV) inhibitors are expected to become a new type of antidiabetic drugs. Most known DPP-IV inhibitors often resemble the dipeptide cleavage products, with a proline mimic at the P I site. As off-target inhibitions of DPP8 and/or DPP9 have shown profound toxicities in the in vivo studies, it is important to develop selective DPP-IV inhibitors for clinical usage. To achieve this, a new class of 2-[3-[[2-[(2S)-2-cyano-1-pyrrolidinyl]-2-oxoethyl]amino]-1-oxopropyl]-based DPP-IV inhibitors was synthesized. SAR studies resulted in a number of DPP-IV inhibitors, having IC50 values of < 50 nM with excellent selectivity over both DPP8 (IC50 > 100 mu M) and DPP-II (IC50 > 30 mu M). Compound 21a suppressed the blood glucose elevation after an oral glucose challenge in Wistar rats and also inhibited plasma DPP-IV activity for up to 4 h in BALB/c mice. The results show that compound 21a possesses in vitro and in vivo activities comparable to those of NVP-LAF237 (4), which is in clinical development. |
| Keywords: | Chemistry, Medicinal |
| Date: | 2006-01-12 |
| Relation: | Journal of Medicinal Chemistry. 2006 Jan;49(1):373-380. |
| Link to: | http://dx.doi.org/10.1021/jm0507781 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-2623&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000234575300038 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=30444442517 |
| Appears in Collections: | [蔣維棠] 期刊論文
[伍素瑩] 期刊論文
[李秀珠] 期刊論文
[謝興邦] 期刊論文
[趙宇生(2002-2013)] 期刊論文
[陳新(2002-2015)] 期刊論文
[陳炯東] 期刊論文
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| 000234575300038.pdf | | 112Kb | Adobe PDF | 1022 | View/Open |
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