| Title : Discovery of beta-homophenylalanine based pyrrolidin-2-ylmethyl amides and sulfonamides as highly potent and selective inhibitors of dipeptidyl peptidase IV - Nordhoff_2009_Bioorg.Med.Chem.Lett_19_4201 |
| Author(s) : Nordhoff S , Cerezo-Galvez S , Deppe H , Hill O , Lopez-Canet M , Rummey C , Thiemann M , Matassa VG , Edwards PJ , Feurer A |
| Ref : Bioorganic & Medicinal Chemistry Lett , 19 :4201 , 2009 |
|
Abstract :
Modifications of DPP-4 inhibitor 5, that was discovered by structure based design, are described and structure-activity relationships discussed. With analogue 7k one of the most potent non-covalent inhibitors of DPP-4 reported to date (IC(50)=0.38nM) was discovered. X-ray structure of inhibitor 7k bound to DPP-4 revealed a hydrogen bonding interaction with Q553. First successful efforts in balancing overall properties, as demonstrated by improved metabolic stability, highlight the potential of this series. |
| PubMedSearch : Nordhoff_2009_Bioorg.Med.Chem.Lett_19_4201 |
| PubMedID: 19515557 |
| Gene_locus related to this paper: human-DPP4 |
| Inhibitor | FPB-derived-7k |
| Gene_locus | human-DPP4 |
| Structure | 3H0C |
Nordhoff S, Cerezo-Galvez S, Deppe H, Hill O, Lopez-Canet M, Rummey C, Thiemann M, Matassa VG, Edwards PJ, Feurer A (2009)
Discovery of beta-homophenylalanine based pyrrolidin-2-ylmethyl amides and sulfonamides as highly potent and selective inhibitors of dipeptidyl peptidase IV
Bioorganic & Medicinal Chemistry Lett
19 :4201
Nordhoff S, Cerezo-Galvez S, Deppe H, Hill O, Lopez-Canet M, Rummey C, Thiemann M, Matassa VG, Edwards PJ, Feurer A (2009)
Bioorganic & Medicinal Chemistry Lett
19 :4201