2,6-Diaryl-4-acylaminopyrimidines as potent and selective adenosine A2A antagonists with improved solubility and metabolic stability

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 20, 2008, Pages 5402-5405

  Moorjani, Manisha ^a   Luo, Zhiyong ^a   Lin, Emily ^a   Vong, Binh G ^a   Chen, Yongsheng ^a   Zhang, Xiaohu ^a   Rueter, Jaimie K ^a   Gross, Raymond S ^a   Lanier, Marion C ^a   Tellew, John E ^a   Williams, John P ^a   Lechner, Sandra M ^b   Malany, Siobhan ^c   Santos, Mark ^c   Crespo, María I ^d   Díaz, José Luis ^d   Saunders, John ^a   Slee, Deborah H ^a  

^a Neurocrine Biosciences ^*  (United States)

^b NEUROCRINE BIOSCIENCES INC   (United States)

^c Neurocrine Biosciences   (United States)

^d NONE   (Spain)

Author keywords

A2A antagonists; Adenosine receptor; Parkinson's disease

Indexed keywords

3 FLUORO 5 HYDROXYPHENYLBORONIC ACID; 4 [2 [7 AMINO 2 (2 FURYL) 1,2,4 TRIAZOLO[2,3 A][1,3,5]TRIAZIN 5 YLAMINO]ETHYL]PHENOL; ADENOSINE A2A RECEPTOR ANTAGONIST; HALOPERIDOL; ISTRADEFYLLINE; POLYCYCLIC AROMATIC HYDROCARBON DERIVATIVE; PYRIMIDINE DERIVATIVE; SCH 420814; UNCLASSIFIED DRUG;

ARTICLE; CATALEPSY; CHEMICAL REACTION; CONTROLLED STUDY; DRUG POTENCY; DRUG SOLUBILITY; DRUG STABILITY; ENANTIOMER; HUMAN; HUMAN CELL; ISOMERISM; PH; REACTION ANALYSIS; STRUCTURE ACTIVITY RELATION; SUZUKI REACTION;

AMINOPYRIDINES; CHEMISTRY, PHARMACEUTICAL; DRUG DESIGN; HALOPERIDOL; HUMANS; HYDROGEN-ION CONCENTRATION; INHIBITORY CONCENTRATION 50; MODELS, CHEMICAL; PARKINSON DISEASE; PROTEIN BINDING; PYRIMIDINES; RECEPTOR, ADENOSINE A1; RECEPTOR, ADENOSINE A2A; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 53549094121     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.09.048     Document Type: Article

References (20)

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15. General experimental details for this assay may be found in the following reference. Slee D.H., Zhang X., Moorjani M., Lin E., Lanier M.C., Chen Y., Rueter J.K., Lechner S.M., Markison S., Malany S., Joswig T., Santos M., Gross R.S., Williams J.P., Castro-Palomino J.C., Crespo M.I., Prat M., Gual S., Díaz J.L., Jalali K., Sai Y., Zuo Z., Yang C., Wen J., O'Brien Z., and Saunders J. J. Med. Chem. 51 (2008) 400
16. To determine solubility of compounds, approximately 1 mg of sample was weighed into a 15 mL Falcon Centrifuge tube, and the weight recorded to 0.001 mg. Assay medium, (200 μL, Phosphate Buffer Solution pH 8.0) was added and the sample sonicated for 10 min, then shaken overnight. The sample was then centrifuged and the supernatant was analyzed by HPLC to determine the concentration of sample in solution. The concentration in solution was then calculated based on a standard curve generated from known dilutions of authentic sample.
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19. 50 < 30 μM were assayed in 2 or 3 experiments.
20. i values were highly reproducible, the standard deviations were less than or equal to 20%. All compounds reported were assayed in 3-6 independent experiments.