| Title : Design, synthesis and biological evaluation of hetero-aromatic moieties substituted pyrrole-2-carbonitrile derivatives as dipeptidyl peptidase IV inhibitors - Ji_2014_Eur.J.Med.Chem_75C_111 |
| Author(s) : Ji X , Su M , Wang J , Deng G , Deng S , Li Z , Tang C , Li J , Zhao L , Jiang H , Liu H |
| Ref : Eur Journal of Medicinal Chemistry , 75C :111 , 2014 |
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Abstract :
A series of novel hetero-aromatic moieties substituted alpha-amino pyrrole-2-carbonitrile derivatives was designed and synthesized based on structure-activity relationships (SARs) of pyrrole-2-carbonitrile inhibitors. All compounds demonstrated good dipeptidyl peptidase IV (DPP4) inhibitory activities (IC50 = 0.004-113.6 muM). Moreover, compounds 6h (IC50 = 0.004 muM) and 6n (IC50 = 0.01 muM) showed excellent inhibitory activities against DPP4, good selectivity (compound 6h, selective ratio: DPP8/DPP4 = 450.0; DPP9/DPP4 = 375.0; compound 6n, selective ratio: DPP8/DPP4 = 470.0; DPP9/DPP4 = 750.0) and good efficacy in an oral glucose tolerance test in ICR mice. Furthermore, compounds 6h and 6n demonstrated moderate PK properties (compound 6h, F% = 37.8%, t1/2 = 1.45 h; compound 6n, F% = 16.8%, t1/2 = 3.64 h). |
| PubMedSearch : Ji_2014_Eur.J.Med.Chem_75C_111 |
| PubMedID: 24531224 |
Ji X, Su M, Wang J, Deng G, Deng S, Li Z, Tang C, Li J, Zhao L, Jiang H, Liu H (2014)
Design, synthesis and biological evaluation of hetero-aromatic moieties substituted pyrrole-2-carbonitrile derivatives as dipeptidyl peptidase IV inhibitors
Eur Journal of Medicinal Chemistry
75C :111
Ji X, Su M, Wang J, Deng G, Deng S, Li Z, Tang C, Li J, Zhao L, Jiang H, Liu H (2014)
Eur Journal of Medicinal Chemistry
75C :111