SAR studies of C2 ethers of 2H-pyrano[2,3-d]pyrimidine-2,4,7(1H,3H)-triones as nicotinic acid receptor (NAR) agonist.

Article Details

Citation

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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
NiacinHydroxycarboxylic acid receptor 2EC 50 (nM)100N/AN/ADetails