Sutton_2012_Bioorg.Med.Chem.Lett_22_1464

Reference

Title : Novel heterocyclic DPP-4 inhibitors for the treatment of type 2 diabetes. - Sutton_2012_Bioorg.Med.Chem.Lett_22_1464
Author(s) : Sutton JM , Clark DE , Dunsdon SJ , Fenton G , Fillmore A , Harris NV , Higgs C , Hurley CA , Krintel SL , Mackenzie RE , Duttaroy A , Gangl E , Maniara W , Sedrani R , Namoto K , Ostermann N , Gerhartz B , Sirockin F , Trappe J , Hassiepen U , Baeschlin DK
Ref : Bioorganic & Medicinal Chemistry Lett , 22 :1464 , 2012
Abstract :

Novel deazaxanthine-based DPP-4 inhibitors have been identified that are potent (IC(50) <10nM) and highly selective versus other dipeptidyl peptidases. Their synthesis and SAR are reported, along with initial efforts to improve the PK profile through decoration of the deazaxanthine core. Optimisation of compound 3a resulted in the identification of compound (S)-4i, which displayed an improved in vitro and ADME profile. Further enhancements to the PK profile were possible by changing from the deazahypoxanthine to the deazaxanthine template, culminating in compound 12g, which displayed good ex vivo DPP-4 inhibition and a superior PK profile in rat, suggestive of once daily dosing in man.

PubMedSearch : Sutton_2012_Bioorg.Med.Chem.Lett_22_1464
PubMedID: 22177783
Gene_locus related to this paper: human-DPP4

Related information

Inhibitor CHEMBL1951424
Gene_locus human-DPP4
Structure 4A5S

Citations formats

Sutton JM, Clark DE, Dunsdon SJ, Fenton G, Fillmore A, Harris NV, Higgs C, Hurley CA, Krintel SL, Mackenzie RE, Duttaroy A, Gangl E, Maniara W, Sedrani R, Namoto K, Ostermann N, Gerhartz B, Sirockin F, Trappe J, Hassiepen U, Baeschlin DK (2012)
Novel heterocyclic DPP-4 inhibitors for the treatment of type 2 diabetes.
Bioorganic & Medicinal Chemistry Lett 22 :1464

Sutton JM, Clark DE, Dunsdon SJ, Fenton G, Fillmore A, Harris NV, Higgs C, Hurley CA, Krintel SL, Mackenzie RE, Duttaroy A, Gangl E, Maniara W, Sedrani R, Namoto K, Ostermann N, Gerhartz B, Sirockin F, Trappe J, Hassiepen U, Baeschlin DK (2012)
Bioorganic & Medicinal Chemistry Lett 22 :1464