A adenosine receptor antagonists

Li AH, Moro S, Melman N, Ji XD, Jacobson KA (1998) Structure-activity relationships and molecular modelling of 3, 5-diacyl-2, 4-dialkylpyridine derivatives as selective A, adenosine receptor antagonists. J Med Chem 41 3186-3201 Li AH, Moro S, Forsyth N, Melman N, Ji XD, Jacobson KA (1999) Synthesis, CoMFA analysis, and receptor docking of 3, 5-diacyl-2, 4-dialkylpyridine derivatives as selective A3 adenosine receptor antagonists. J Med Chem 42 706-721... 

A. Crespo, A. El Maatougui, P. Biagini, J. Azuaje, A. Coelho, J. Brea, M. I. Loza, M. I. Cadavid, X. Garcia-Mera, H. Gutierrez-de-Teran, E. Sotelo, ACS Med. Chem. Lett. 2013,4, 1031-1036. Discovery of 3,4-dihydropyrimidin-2(l//)-ones as a novel class of potent and selective A adenosine receptor antagonists. 

The main mechanism of action of caffeine occurs via the blockade of adenosine receptors in the CNS. Adenosine is an autacoid, which is involved in the modulation of behavior, oxygenation of cells, and dilatation of cerebral and coronary blood vessels and indirectly inhibits the release of dopamine. The blockade of adenosine receptors by caffeine increases the activity of dopamine, which is implicated in the effects of caffeine (91). The question that arises from this observation is to know whether or not adenosine antagonists hold potential for the treatment of Parkinsonism, and further study on the adenosine receptor antagonists from medicinal plants should be encouraged. A possible source for such agents could be the medicinal flora of Asia and the Pacific, among which is the family Sapindaceae. 

Fredholm B. B., Lindstrom K (1999). Autoradiographic comparison of the potency of several structurally unrelated adenosine receptor antagonists at adenosine Al and A(2A) receptors. Eur. J. Pharmacol. 380, 197-202. 

Harper L. K., Beckett S. R., Marsden C. A., McCreary A. C., Alexander S. P. (2006). Effects of the A(2A) adenosine receptor antagonist KW6002 in the nucleus accumbens in vitro and in vivo. Pharmacol Biochem. Behav. in press. 

J. Leppanen, J. Huuskonen, J. Savolainen, T. Nevalainen, H. Taipale, J. Vepsalainen, J. Gynther, T. Jarvinen, Synthesis of a Water-Soluble Prodrug of Entacapone , Bioorg. Med. Chem. Lett. 2000, 10, 1967-1969 R. Sauer, J. Maurinsh, U. Reith, F. Ftille, K. N. Klotz, C. E. Muller, Water-Soluble Phosphate Prodrugs of l-Propargyl-8-styryl-xanthine Derivatives, A2A-Selective Adenosine Receptor Antagonists , J. Med. Chem. 2000, 43, 440-448. 

Some substituted 3-thiomethyltriazole derivatives show antithyroid activity <92EJM359> and some 7V-l-methylcarboxylates mimic the action of penicillins <92EJM193>. An Aja adenosine receptor antagonist containing a triazole ring has been described <94BMC2539>. 

Increased delivery of salt to the TAL leads to activation of the macula densa and a reduction in glomerular filtration rate (GFR) by tubuloglomerular (TG) feedback. The mechanism of this feedback is secretion of adenosine by macula densa cells, which locally causes afferent arteriolar vasoconstriction. This vasoconstriction reduces GFR. Tubuloglomerular feedback-mediated reduction in GFR exacerbates the reduction that was initially caused by decreased cardiac output. Recent work with adenosine receptor antagonists (eg, rolofylline) has shown that it will soon be possible to circumvent this complication of diuretic therapy in heart failure patients. Using rolofylline with a diuretic will make it possible to produce an effective diuresis in patients with heart failure without causing renal decompensation. 

Baraldi, P. G., Cacciari, B., Romagnoli, R., Spalluto, G., Monopoli, A., Ongini, E., Varani, K., Borea, P. A. 7-Substituted 5-amino-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as A2A adenosine receptor antagonists a study on the importance of modifications at the side chain on the activity and solubility, J. Med. Chem. 2002, 45, 115-126. 

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