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7-Oxopyrrolopyridine-derived DPP4 inhibitors-mitigation of CYP and hERG liabilities via introduction of polar functionalities in the active site.

Abstract：

:Design, synthesis, and SAR of 7-oxopyrrolopyridine-derived DPP4 inhibitors are described. The preferred stereochemistry of these atropisomeric biaryl analogs has been identified as Sa. Compound (+)-3t, with a K(i) against DPP4, DPP8, and DPP9 of 0.37 nM, 2.2, and 5.7 μM, respectively, showed a significant improvement in insulin response after single doses of 3 and 10 μmol/kg in ob/ob mice.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Wang W,Devasthale P,Wang A,Harrity T,Egan D,Morgan N,Cap M,Fura A,Klei HE,Kish K,Weigelt C,Sun L,Levesque P,Li YX,Zahler R,Kirby MS,Hamann LG

doi

10.1016/j.bmcl.2011.09.074

subject

Has Abstract

pub_date

2011-11-15 00:00:00

pages

6646-51

issue

22

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)01318-7

journal_volume

21

pub_type

杂志文章

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