SAR studies of C2 ethers of 2H-pyrano[2,3-d]pyrimidine-2,4,7(1H,3H)-triones as nicotinic acid receptor (NAR) agonist.
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Huang X, Su J, Rao AU, Tang H, Zhou W, Zhu X, Chen X, Liu Z, Huang Y, Degrado S, Xiao D, Qin J, Aslanian R, McKittrick BA, Greenfeder S, Heek Mv, Chintala M, Palani A
SAR studies of C2 ethers of 2H-pyrano[2,3-d]pyrimidine-2,4,7(1H,3H)-triones as nicotinic acid receptor (NAR) agonist.
Bioorg Med Chem Lett. 2012 Jan 15;22(2):854-8. doi: 10.1016/j.bmcl.2011.12.041. Epub 2011 Dec 13.
- PubMed ID
- 22209457 [ View in PubMed]
- Abstract
Based on in house screening lead compound 1 for the NAR project, SAR studies have been focused on the modification of the C2 ethers of the pyrimidinedione core structure. In this effort, an unpredictable SAR trend was overcome in the alkyl ether and arylalkyl ether series to identify compound 24 with improved in vitro activity compared to nicotinic acid. More consistent and predictable SAR was achieved in the propargyl ether series. Lead compound 41 was identified with good in vitro and in vivo activity in rat, and much improved rat PK profile.
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- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Niacin Hydroxycarboxylic acid receptor 2 EC 50 (nM) 100 N/A N/A Details