Inhibitor Report for: CHEMBL233360 General
Type Trifluoro , Triazol Chemical_Nomenclature (1S,2R,5S)-5-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-2-(2,4,5-trifluorophenyl)cyclohexan-1-amine Canonical SMILES C1CC(C(CC1N2CCN3C(=NN=C3C(F)(F)F)C2)N)C4=CC(=C(C=C4F)F)F InChI InChI=1S/C18H19F6N5/c19-12-7-14(21)13(20)6-11(12)10-2-1-9(5-15(10)25)28-3-4-29-16(8-28)26-27-17(29)18(22,23)24/h6-7,9-10,15H,1-5,8,25H2/t9-,10+,15-/m0/s1 InChIKey CNKRZILQBKJWDS-WMFXKJRFSA-N Other name(s) CHEBI:39959 ; SCHEMBL3904882 ; BDBM50212927 ; CHEMBL233360 (15) ; DB07072 ; 417
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Target
Families | CHEMBL233360 ligand of proteins in family: DPP4N_Peptidase_S9 Stucture | 1 structure : 2P8S : Human dipeptidyl peptidase IV/CD26 in complex with a cyclohexalamine inhibitor Protein | human-DPP4
References:
Title: Rational design of a novel, potent, and orally bioavailable cyclohexylamine DPP-4 inhibitor by application of molecular modeling and X-ray crystallography of sitagliptinBiftu T , Scapin G , Singh S , Feng D , Becker JW , Eiermann G , He H , Lyons K , Patel S and Weber AE <7 more author(s)> Biftu T , Scapin G , Singh S , Feng D , Becker JW , Eiermann G , He H , Lyons K , Patel S , Petrov A , Sinha-Roy R , Zhang B , Wu J , Zhang X , Doss GA , Thornberry NA , Weber AE (- 7) Ref: Bioorganic & Medicinal Chemistry Lett, 17 :3384, 2007 : PubMed Abstract ESTHER: Biftu_2007_Bioorg.Med.Chem.Lett_17_3384 PubMedSearch: Biftu 2007 Bioorg.Med.Chem.Lett 17 3384 PubMedID: 17433672 Gene_locus related to this paper: human-DPP4 Inhibitor(s) related to this paper: CHEMBL233360 Abstract
Molecular modeling was used to design a rigid analog of sitagliptin 1. The X-ray crystal structure of sitagliptin bound to DPP-4 suggested that the central beta-amino butyl amide moiety could be replaced with a cyclohexylamine group. This was confirmed by structural analysis and the resulting analog 2a was synthesized and found to be a potent DPP-4 inhibitor (IC(50)=21 nM) with excellent in vivo activity and pharmacokinetic profile.
