371230-35-2Relevant academic research and scientific papers
Synthesis and evaluation of N-substituted 2-amino-4,5-diarylpyrimidines as selective adenosine A1receptor antagonists
Alachouzos, Georgios,Lenselink, Eelke B.,Mulder-Krieger, Thea,de Vries, Henk,IJzerman, Adriaan P.,Louvel, Julien
, p. 586 - 602 (2016/10/12)
We report the synthesis and biological evaluation of new 2-amino-4,5-diarylpyrimidines as selective antagonists at the adenosine A1receptor. The scaffold they are based upon is a deaza variation of a previously reported collection of 3-amino-5,6-diaryl-1,2,4-triazines, members of which had a subnanomolar affinity but limited selectivity over the A2Asubtype. Initially, similar structure-affinity relationships at the 5-aryl ring were established, and then emphasis was put on increasing selectivity at the hA1AR by introducing substituents on the N2-position, all the while maintaining a nanomolar affinity. Compound 3z, bearing a trans 4-hydroxycyclohexyl substituent, was identified as a potent (Ki(hA1AR) = 7.7 nM) and selective (Ki(hA2AAR) = 1389 nM) antagonist at the human adenosine A1receptor. Computational docking was effected at the A1and A2Asubtypes, rationalizing the effect of the 4-hydroxycyclohexyl substituent on selectivity, in relation with the nature of the substituent on the 5-position of the pyrimidine.
Small molecule that reverses dexamethasone resistance in t-cell acute lymphoblastic leukemia (T-ALL)
Cantley, Alexandra M.,Welsch, Matthew,Ambesi-Impiombato, Alberto,Sanchez-Martin, Marta,Kim, Mi-Yeon,Bauer, Andras,Ferrando, Adolfo,Stockwell, Brent R.
supporting information, p. 754 - 759 (2014/08/05)
Glucocorticoids are one of the most utilized and effective therapies in treating T-cell acute lymphoblastic leukemia. However, patients often develop resistance to glucocorticoids, rendering these therapies ineffective. We screened 9517 compounds, selected for their lead-like properties, chosen from among 3372615 compounds, against a dexamethasone-resistant T-ALL cell line to identify small molecules that reverse glucocorticoid resistance. We synthesized analogues of the most effective compound, termed J9, from the screen in order to define the scaffolds structure-activity relationship. Active compounds restored sensitivity to glucocorticoids through upregulation of the glucocorticoid receptor. This compound and mechanism may provide a strategy for overcoming glucocorticoid resistance in patients with T-ALL.
Medicinal compositions promoting bowel movement
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, (2008/06/13)
The present invention provides a medicament having a gentle but strong defecation-promoting action without causing diarrhea. That is, it provides a defecation-promoting agent comprising a compound having an adenosine A2 receptor antagonism, pre
