Inhibitor Report for: 4-aminocyclohexylalanine-derivative-25 alpha amino acid inhibitor
General
Type Pyrrolidine Chemical_Nomenclature N-[4-[(2S,3S)-3-amino-4-[(3S)-3-fluoropyrrolidin-1-yl]-4-oxobutan-2-yl]cyclohexyl]-N-methylacetamide Canonical SMILES CC(C1CCC(CC1)N(C)C(=O)C)C(C(=O)N2CCC(C2)F)N InChI InChI=1S/C17H30FN3O2/c1-11(16(19)17(23)21-9-8-14(18)10-21)13-4-6-15(7-5-13)20(3)12(2)22/h11,13-16H,4-10,19H2,1-3H3/t11-,13?,14-,15?,16-/m0/s1 InChIKey BZFQBRSDORUYAB-IZMWZWCESA-N Other name(s) 277 ; N-(Trans-4-{(1s,2s)-2-Amino-3-[(3s)-3-Fluoropyrrolidin-1-Yl]-1-Methyl-3-Oxopropyl}cyclohexyl)-N-Methylacetamide ; CHEMBL1182555 ; CHEMBL1229855 ; SCHEMBL13412200 ; BDBM17323 ; DB06939
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Target
Families | 4-aminocyclohexylalanine-derivative-25 ligand of proteins in family: DPP4N_Peptidase_S9 Stucture | 1 structure : 2OPH : Human dipeptidyl peptidase IV in complex with an alpha amino acid inhibitor Protein | human-DPP4
References:
Title: 4-aminophenylalanine and 4-aminocyclohexylalanine derivatives as potent, selective, and orally bioavailable inhibitors of dipeptidyl peptidase IV
Duffy JL , Kirk BA , Wang L , Eiermann GJ , He H , Leiting B , Lyons KA , Patel RA , Patel SB and Weber AE <4 more author(s)>
Duffy JL , Kirk BA , Wang L , Eiermann GJ , He H , Leiting B , Lyons KA , Patel RA , Patel SB , Petrov A , Scapin G , Wu JK , Thornberry NA , Weber AE (- 4)
Ref: Bioorganic & Medicinal Chemistry Lett, 17 :2879, 2007 : PubMed Abstract ESTHER: Duffy_2007_Bioorg.Med.Chem.Lett_17_2879 PubMedSearch: Duffy 2007 Bioorg.Med.Chem.Lett 17 2879 PubMedID: 17350841 Gene_locus related to this paper: human-DPP4 Inhibitor(s) related to this paper: 4-aminocyclohexylalanine-derivative-25 Abstract
A novel series of 4-aminophenylalanine and 4-aminocyclohexylalanine derivatives were designed and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4). The phenylalanine series afforded compounds such as 10 that were potent and selective (DPP-4, IC(50)=28nM), but exhibited limited oral bioavailability. The corresponding cyclohexylalanine derivatives such as 25 afforded improved PK exposure and efficacy in a murine OGTT experiment. The X-ray crystal structure of 25 bound to the DPP-4 active site is presented.