Discovery of novel 2-[2-(3-hydroxy-pyridin-2-yl)-thiazol-4-yl]-acetamide derivatives as HIF prolyl 4-hydroxylase inhibitors; SAR, synthesis and modeling evaluation.

Abstract:

:The design, synthesis, and capacity to inhibit HIF prolyl 4-hydroxylases (PHDs) are described for 2-[2-(3-hydroxy-pyridin-2-yl)-thiazol-4-yl]-acetamide analogs. These analogs revealed two kinds of novel scaffolds as PHD2 inhibitors. Synthetic routes were developed for the preparation of their analogs containing the new scaffolds. In addition, the structure-activity relationship (SAR) of the 2-[2-(3-hydroxy-pyridin-2-yl)-thiazol-4-yl]-acetamide derivatives and their biological activities were reported. The complex structure of compound 18 with PHD2 was also obtained for the purpose of more efficient lead optimization.

journal_name

Bioorg Med Chem Lett

authors

Hong YR,Kim HT,Ro S,Cho JM,Lee SH,Kim IS,Jung YH

doi

10.1016/j.bmcl.2014.05.003

subject

Has Abstract

pub_date

2014-07-15 00:00:00

pages

3142-5

issue

14

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(14)00490-9

journal_volume

24

pub_type

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