Advanced

HTS followed by NMR based counterscreening. Discovery and optimization of pyrimidones as reversible and competitive inhibitors of xanthine oxidase.

Evenäs, Johan; Edfeldt, Fredrik; Lepistö, Matti; Svitacheva, Naila; Synnergren, Anna; Lundquist, Britta; Gränse, Mia LU ; Rönnholm, Anna LU ; Varga, Mikael and Wright, John, et al. (2014) In Bioorganic & Medicinal Chemistry Letters 24(5). p.1315-1321
Abstract
The identification of novel, non-purine based inhibitors of xanthine oxidase is described. After a high-throughput screening campaign, an NMR based counterscreen was used to distinguish actives, which interact with XO in a reversible manner, from assay artefacts. This approach identified pyrimidone 1 as a reversible and competitive inhibitor with good lead-like properties. A hit to lead campaign gave compound 41, a nanomolar inhibitor of hXO with efficacy in the hyperuricemic rat model after oral dosing.
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Bioorganic & Medicinal Chemistry Letters
volume
24
issue
5
pages
1315 - 1321
publisher
Elsevier
external identifiers
  • pmid:24508129
  • wos:000331705200014
  • scopus:84894572482
ISSN
1090-2120
DOI
10.1016/j.bmcl.2014.01.050
language
English
LU publication?
yes
id
5a4f4720-8d8d-4e23-8d03-95feb4a534b3 (old id 4335129)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24508129?dopt=Abstract
date added to LUP
2014-03-06 13:55:50
date last changed
2017-10-22 03:23:30
@article{5a4f4720-8d8d-4e23-8d03-95feb4a534b3,
  abstract     = {The identification of novel, non-purine based inhibitors of xanthine oxidase is described. After a high-throughput screening campaign, an NMR based counterscreen was used to distinguish actives, which interact with XO in a reversible manner, from assay artefacts. This approach identified pyrimidone 1 as a reversible and competitive inhibitor with good lead-like properties. A hit to lead campaign gave compound 41, a nanomolar inhibitor of hXO with efficacy in the hyperuricemic rat model after oral dosing.},
  author       = {Evenäs, Johan and Edfeldt, Fredrik and Lepistö, Matti and Svitacheva, Naila and Synnergren, Anna and Lundquist, Britta and Gränse, Mia and Rönnholm, Anna and Varga, Mikael and Wright, John and Wei, Min and Yue, Sherrie and Wang, Junfeng and Li, Chong and Li, Xuan and Chen, Gang and Liao, Yong and Lv, Gang and Tjörnebo, Ann and Narjes, Frank},
  issn         = {1090-2120},
  language     = {eng},
  number       = {5},
  pages        = {1315--1321},
  publisher    = {Elsevier},
  series       = {Bioorganic & Medicinal Chemistry Letters},
  title        = {HTS followed by NMR based counterscreening. Discovery and optimization of pyrimidones as reversible and competitive inhibitors of xanthine oxidase.},
  url          = {http://dx.doi.org/10.1016/j.bmcl.2014.01.050},
  volume       = {24},
  year         = {2014},
}