| Title : (2S,4S)-1-[2-(1,1-dimethyl-3-oxo-3-pyrrolidin-1-yl-propylamino)acetyl]-4-fluoro-p yrrolidine-2-carbonitrile: a potent, selective, and orally bioavailable dipeptide-derived inhibitor of dipeptidyl peptidase IV - Yeh_2010_Bioorg.Med.Chem.Lett_20_3596 |
| Author(s) : Yeh TK , Tsai TY , Hsu T , Cheng JH , Chen X , Song JS , Shy HS , Chiou MC , Chien CH , Tseng YJ , Huang CY , Yeh KC , Huang YL , Huang CH , Huang YW , Wang MH , Tang HK , Chao YS , Chen CT , Jiaang WT |
| Ref : Bioorganic & Medicinal Chemistry Lett , 20 :3596 , 2010 |
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Abstract :
A series of 2-[3-[2-[(2S)-2-cyano-1-pyrrolidinyl]-2-oxoethylamino]-3-methyl-1-oxobutyl]-based DPP-IV inhibitors with various monocyclic amines were synthesized. The structure-activity relationships (SAR) led to the discovery of potent DPP-IV inhibitors, having IC(50) values of <100 nM with excellent selectivity over the closely related enzymes, DPP-II, DPP8, DPP9 and FAP (IC(50)>20 microM). Of these compounds, the analogues 12a, 12h and 12i exhibited a long-lasting ex vivo DPP-IV inhibition in rats. |
| PubMedSearch : Yeh_2010_Bioorg.Med.Chem.Lett_20_3596 |
| PubMedID: 20483603 |
| Inhibitor | Prusogliptin |
Yeh TK, Tsai TY, Hsu T, Cheng JH, Chen X, Song JS, Shy HS, Chiou MC, Chien CH, Tseng YJ, Huang CY, Yeh KC, Huang YL, Huang CH, Huang YW, Wang MH, Tang HK, Chao YS, Chen CT, Jiaang WT (2010)
(2S,4S)-1-[2-(1,1-dimethyl-3-oxo-3-pyrrolidin-1-yl-propylamino)acetyl]-4-fluoro-p yrrolidine-2-carbonitrile: a potent, selective, and orally bioavailable dipeptide-derived inhibitor of dipeptidyl peptidase IV
Bioorganic & Medicinal Chemistry Lett
20 :3596
Yeh TK, Tsai TY, Hsu T, Cheng JH, Chen X, Song JS, Shy HS, Chiou MC, Chien CH, Tseng YJ, Huang CY, Yeh KC, Huang YL, Huang CH, Huang YW, Wang MH, Tang HK, Chao YS, Chen CT, Jiaang WT (2010)
Bioorganic & Medicinal Chemistry Lett
20 :3596