Inhibitor Report for: FPB-derived-7k Reversed Amide Inhibitor: reverse binding to DPP-4 when compared to classical DPP-4 inhibitors General
Type Pyrrolidine Chemical_Nomenclature N-[[(2S)-1-[(3R)-3-amino-4-(3-chlorophenyl)butanoyl]pyrrolidin-2-yl]methyl]-3-methylsulfonylbenzamide Canonical SMILES CS(=O)(=O)C1=CC=CC(=C1)C(=O)NCC2CCCN2C(=O)CC(CC3=CC(=CC=C3)Cl)N InChI InChI=1S/C23H28ClN3O4S/c1-32(30,31)21-9-3-6-17(13-21)23(29)26-15-20-8-4-10-27(20)22(28)14-19(25)12-16-5-2-7-18(24)11-16/h2-3,5-7,9,11,13,19-20H,4,8,10,12,14-15,25H2,1H3,(H,26,29)/t19-,20+/m1/s1 InChIKey QRGBOABBMKYMLG-UXHICEINSA-N Other name(s) PS4 ; CHEMBL564249 ; N-({(2s)-1-[(3r)-3-Amino-4-(3-Chlorophenyl)butanoyl]pyrrolidin-2-Yl}methyl)-3-(Methylsulfonyl)benzamide ; SCHEMBL8289096 ; BDBM50296131 ; DB08429 ; N-(((S)-1-((R)-3-amino-4-(3-chlorophenyl)butanoyl)pyrrolidin-2-yl)methyl)-3-(methylsulfonyl)benzamide
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Target
Families | FPB-derived-7k ligand of proteins in family: DPP4N_Peptidase_S9 Stucture | 1 structure : 3H0C : Crystal Structure of Human Dipeptidyl Peptidase IV (CD26) in Complex with a Reversed Amide Inhibitor Protein | human-DPP4
References:
Title: Discovery of beta-homophenylalanine based pyrrolidin-2-ylmethyl amides and sulfonamides as highly potent and selective inhibitors of dipeptidyl peptidase IVNordhoff 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 : PubMed Abstract ESTHER: Nordhoff_2009_Bioorg.Med.Chem.Lett_19_4201 PubMedSearch: Nordhoff 2009 Bioorg.Med.Chem.Lett 19 4201 PubMedID: 19515557 Gene_locus related to this paper: human-DPP4 Inhibitor(s) related to this paper: FPB-derived-7k 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.
