Development of 2,4-diaminopyrimidine derivatives as novel SNSR4 antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 7, 2011, Pages 2102-2105

  Bayrakdarian, Malken ^a   Butterworth, Joanne ^a   Hu, Yun Jin ^a   Santhakumar, Vijayaratnam ^a   Tomaszewski, Mirosław J ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

BAM 8 22; Diamino pyrimidine; MrgX1; Sensory neuron specific receptor; SNSR4

Indexed keywords

2,4 DIAMINOPYRIMIDINE DERIVATIVE; G PROTEIN COUPLED RECEPTOR; N ETHYL N (4 PYRIDYL METHYL)AMIDE; PIPERAZINE ACETYL AMIDE DERIVATIVE; PYRIMIDINE DERIVATIVE; QUINAZOLINE DERIVATIVE; SENSORY NEURON SPECIFIC RECEPTOR 4; UNCLASSIFIED DRUG;

ALKYLATION; ANALGESIC ACTIVITY; ARTICLE; CATALYSIS; DEMETHYLATION; DRUG POTENCY; DRUG SCREENING; DRUG SOLUBILITY; DRUG STRUCTURE; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

INHIBITORY CONCENTRATION 50; PYRIMIDINES; RECEPTORS, CELL SURFACE; SENSORY RECEPTOR CELLS;

EID: 79952487827     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.01.138     Document Type: Article

References (11)

1. (a) Marinissen, M. J.; Gutkind, J. S. Trends Pharmacol. Sci. 2001, 22, 368;
2. (b) Stadel, J. M.; Wilson, S.; Bergsma, D. J. Trends Pharmacol. Sci. 1997, 18, 430;
3. (c) Rohrer, D. K.; Kobilka, B. K. Physiol. Rev. 1998, 78, 35;
4. (d) Hopkins, A. L.; Groom, C. R. Nat. Rev. Drug Discov. 2002, 1, 727.
5. Dong, X.; Han, S.; Zylka, M. J.; Simon, M. I.; Anderson, D. J. Cell 2001, 106, 619.
6. Lembo, P. M.; Grazzini, E.; Groblewski, T.; O'Donnell, D.; Roy, M. O.; Zhang, J.; Hoffert, C.; Cao, J.; Schmidt, R.; Pelletier, M. Nat. Neurosci. 2002, 5, 201.
7. (a) Grazzini, E.; Puma, C.; Roy, M.; Yu, X.; O'Donnell, D.; Schmidt, R.; Dautrey, S.; Ducharme, J.; Perkins, M.; Panetta, R.; Laird, J.; Ahmad, S.; Lembo, P. Proc. Natl. Acad. Sci. 2004, 101, 7175;
8. (b) Chen, T.; Cai, Q.; Hong, Y. Neuroscience 2006, 141(2), 965.
9. Kunapuli, P.; Lee, S.; Zheng, W.; Alberts, M.; Kornienko, O.; Mull, R.; Kreamer, A.; Hwang, J.; Simon, M. I.; Strulovici, B. Anal. Biochem. 2006, 351, 50-61.
10. 2) for 60 min prior to start the experiment. The incubation was terminated by washing the cells four times in assay buffer (Hank's BSS, 20 mM HEPES ± 0.1% BSA, pH 7.4.), leaving a residual 25 μl buffer per well. After the washing, the cells were incubated at room temperature for 5-10 min and then transferred to the FLIPR, ready for compound additions. The day of experiment, the reference agonist and compounds were diluted in 3-fold concentration range (10 points serial dilution) for addition by FLIPR instrument. For all calcium assays, a baseline reading was taken for 30 s followed by the addition of 12.5 μl of compounds, resulting in a total well volume of 37.5 μl. Data were collected every 1.6 s for 300 s. The fluorescence emission was read using filter 1 (emission 520-545 nm) by the FLIPR on board CCD camera.
11. Ji, J.; Li, T.; Bunnelle, W. Org. Lett. 2003, 5, 4611.