2,6-Diaryl-4-acylaminopyrimidines as potent and selective adenosine A sub(2A) antagonists with improved solubility and metabolic stability

In this report, the strategy and outcome of expanding SAR exploration to improve solubility and metabolic stability are discussed. Compound 35 exhibited excellent potency, selectivity over A sub(1) and improved solubility of >4 mg/mL at pH 8.0. In addition, compound 35 had good metabolic stabilit...

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Published inBioorganic & medicinal chemistry Vol. 18; no. 20; pp. 5402 - 5405
Main Authors Moorjani, Manisha, Luo, Zhiyong, Lin, Emily, Vong, Binh G, Chen, Yongsheng, Zhang, Xiaohu, Rueter, Jaimie K, Gross, Raymond S, Lanier, Marion C, Tellew, John E, Williams, John P, Lechner, Sandra M, Malany, Siobhan, Santos, Mark, Crespo, Maria I, Diaz, Jose-Luis, Saunders, John, Slee, Deborah H
Format Journal Article
LanguageEnglish
Published 01.10.2008
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Summary:In this report, the strategy and outcome of expanding SAR exploration to improve solubility and metabolic stability are discussed. Compound 35 exhibited excellent potency, selectivity over A sub(1) and improved solubility of >4 mg/mL at pH 8.0. In addition, compound 35 had good metabolic stability with a scaled intrinsic clearance of 3 mL/min/kg (HLM) and demonstrated efficacy in the haloperidol induced catalepsy model.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
content type line 23
ObjectType-Feature-2
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmcl.2008.09.048