• Title of article

    Rational design of a novel, potent, and orally bioavailable cyclohexylamine DPP-4 inhibitor by application of molecular modeling and X-ray crystallography of sitagliptin

  • Author/Authors

    Tesfaye Biftu، نويسنده , , Giovanna Scapin، نويسنده , , Suresh Singh، نويسنده , , Dennis Feng، نويسنده , , Joe W. Becker، نويسنده , , George Eiermann، نويسنده , , Huaibing He، نويسنده , , Kathy Lyons، نويسنده , , Sangita Patel، نويسنده , , Aleksandr Petrov، نويسنده , , Ranabir Sinha-Roy، نويسنده , , Bei Zhang، نويسنده , , Joseph Wu، نويسنده , , Xiaoping Zhang، نويسنده , , George A. Doss، نويسنده , , Nancy A. Thornberry، نويسنده , , Ann E. Weber، نويسنده ,

  • Issue Information
    روزنامه با شماره پیاپی سال 2007
  • Pages
    4
  • From page
    3384
  • To page
    3387
  • 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 β-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 (IC50 = 21 nM) with excellent in vivo activity and pharmacokinetic profile.
  • Keywords
    DPP-4 , sitagliptin , Januvia , Cyclohexylamine
  • Journal title
    Bioorganic & Medicinal Chemistry Letters
  • Serial Year
    2007
  • Journal title
    Bioorganic & Medicinal Chemistry Letters
  • Record number

    798239

    • Link To Document
    https://search.isc.ac/dl/search/defaultta.aspx?DTC=10&DC=798239