کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1361510 981465 2012 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Novel heterocyclic DPP-4 inhibitors for the treatment of type 2 diabetes
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Novel heterocyclic DPP-4 inhibitors for the treatment of type 2 diabetes
چکیده انگلیسی

Novel deazaxanthine-based DPP-4 inhibitors have been identified that are potent (IC50 <10 nM) 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.

Novel deazaxanthine-based DPP-4 inhibitors have been identified that are potent (IC50 <10 nM) 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.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 3, 1 February 2012, Pages 1464–1468
نویسندگان
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