Synthesis of the tritium labeled SCH 58261, a new non-xanthine A2A adenosine receptor antagonist

Baraldi, Pier Giovanni; Cacciari, Barbara; Dionisotti, Silvio; Egan, Judith A.; Spalluto, Giampiero; Zocchi, Cristina

doi:10.1002/(sici)1099-1344(199608)38:8<725::aid-jlcr885>3.0.co;2-g

Cited by 17 publications

(7 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5‐Amino‐7‐(2‐phenylethyl)‐2‐(2‐furyl)‐pyrazolo[4,3‐ e ]‐1,2,4‐triazolo[1,5‐c]pyrimidine (SCH 58261) was synthesized as described previously (Baraldi et al , 1994). [ 3 H]‐SCH 58261 (specific activity 68.6 Ci m m −1 ; radiochemical purity 99%) was obtained by use of the precursor 5‐amino‐7‐[2‐(2′,4′,5′‐tribromo)‐phenylethyl]2‐(2‐furyl)‐pyrazolo[4,3‐ e ]‐1,2,4‐triazolo‐[1,5‐c]pyrimidine (Baraldi et al , 1996). Then, the radio‐labelled form was prepared by NEN‐Dupont (Boston, MA, U.S.A.) through reduction with tritium gas.…”

Section: Methodsmentioning

confidence: 99%

Characterization of human A_2A adenosine receptors with the antagonist radioligand [³H]‐SCH 58261

Dionisotti

Ongini

Zocchi

et al. 1997

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

1 We have characterized the binding of the new potent and selective antagonist radioligand [ 3 H]-5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo [1,5-c] A nity values and rank order of potency of both receptor agonists and antagonists were similar to those previously obtained in human platelet and rat striatal membranes, except for CV 1808 which was more potent than CGS 21680. SCH 58261 was a competitive antagonist at inhibiting NECA-induced adenosine 3' : 5'-cyclic monophosphate (cyclic AMP) accumulation in CHO cells transfected with human A 2A receptors. Good agreement was found between binding and functional data. 6 Thus, the new antagonist radioligand is preferable to the receptor agonist radioligand [ 3 H]-CGS 21680 hitherto used to examine the pharmacology of human cloned A 2A adenosine receptors.

show abstract

Section: Methodsmentioning

confidence: 99%

Characterization of human A_2A adenosine receptors with the antagonist radioligand [³H]‐SCH 58261

Dionisotti

Ongini

Zocchi

et al. 1997

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Intensive efforts have been made over the past few years with the aim to synthesize novel compounds, either xanthine or non-xanthine, interacting selectively with the A 2A adenosine receptor type. Thus, the pyrazolotriazolopyrimidines SCH 58261 (5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo[4,3- e ]-1,2,4-triazolo[1,5- c ]pyrimidine, 1 ) and SCH 63390 (5-amino-7-(3-phenylpropyl)-2-(2-furyl)pyrazolo[4,3- e ]-1,2,4-triazolo[1,5- c ]pyrimidine, 2 ) have been found to be potent and selective adenosine A 2A antagonists, and SCH 58261 is widely used as a tool for characterizing the adenosine A 2A receptor subtype (Chart ). , Moreover, the labeled form of SCH 58261 has been synthesized and well characterized as described in a variety of tissues and cell types. , Another compound of interest is ZM 241385 (4-[2-[[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3- a ][1,3,5]triazin-5-yl]amino]ethyl]phenol, 3 ) which, like SCH 58261, has been derived from the prototype CGS 15943 (5-amino-9-chloro-2-(2-furyl)-1,2,4-triazolo[1,5- c ]quinazoline, 4 ) (Chart ) . ZM 241385 is an A 2A adenosine antagonist endowed with good affinity and selectivity for A 2A vs A 1 , and it is quite hydrophilic, an interesting characteristic because, usually, the A 2A adenosine antagonists are lipophilic compounds.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of a Second Generation of Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as Potent and Selective A_2A Adenosine Receptor Antagonists

Baraldi¹,

Cacciari²,

Spalluto³

et al. 1998

J. Med. Chem.

Self Cite

View full text Add to dashboard Cite

New A2A adenosine receptor antagonists in the series of pyrazolo[4, 3-e]-1,2,4-triazolo[1,5-c]pyrimidines, bearing oxygenated substituents on the phenylalkyl chains on the 7-position, have been synthesized. The compounds were tested in binding and functional assays to evaluate affinity, potency, and selectivity for rat A2A compared to rat A1 and human A3 receptor subtypes. The most interesting compounds (5d,e,h) were tested also in binding to human A1 and A2A adenosine receptors. They showed very good affinity (Ki = 0.94 nM for compound 5h) and interesting selectivity with respect to both rA1 and hA3 (compound 5h: rA1/rA2A = 787, hA3/rA2A > 10 000). These important findings make this new series of compounds the first really selective for A2A adenosine receptors. Thermodynamic parameters were evaluated; all the tested compounds displayed an enthalpy-driven binding as expected for antagonists. Moreover, compound 5h showed a negative entropy value. The highly negative enthalpic and entropic contributions could mean that 5h fits very well in the binding site where, probably, an electrostatic interaction is present associated to a scarce solvent reorganization around the receptor binding site. These compounds deserve to be further developed to assess their potential for treatment of neurodegenerative disorders such as Parkinson's disease.

show abstract

“…,2,4-triazolo[i,5-c]pyrimidine (SCH 58261) was synthesized as described by Baraldi et al (1994). [3H]SCH 58261 (specific activity, 68.6 Ci/mM; radiochemical purity, 99%) was obtained using the precursor 5-amino-7- [2-(2' ,4 ',5 '- (Baraldi et al, 1996). Then the radiolabeled form was prepared by NEN-Du Pont (Boston, MA, U.S.A.) through reduction with tritium gas.…”

mentioning

confidence: 99%

[³H]SCH 58261, a Selective Adenosine A_2A Receptor Antagonist, Is a Useful Ligand in Autoradiographic Studies

Fredholm¹,

Lindström²,

Dionisotti³

et al. 1998

Journal of Neurochemistry

Self Cite

View full text Add to dashboard Cite

We have characterized the new potent and selective nonxanthine adenosine A2A receptor antagonist SCH 58261 as a new radioligand for receptor autoradiography. In autoradiographic studies using agonist radioligands for A2A receptors ([3H]CGS 21680) or A1 receptors (N6‐[3H]cyclohexyladenosine), it was found that SCH 58261 is close to 800‐fold selective for rat brain A2A versus A1 receptors (Ki values of 1.2 nM versus 0.8 µM). Moreover, receptor autoradiography showed that [3H]SCH 58261, in concentrations below 2 nM, binds only to the dopamine‐rich regions of the rat brain, with a KD value of 1.4 (0.8–1.8) nM. The maximal number of binding sites was 310 fmol/mg of protein in the striatum. Below concentrations of 3 nM, the nonspecific binding was <15%. Three adenosine analogues displaced all specific binding of [3H]SCH 58261 with the following estimated Ki values (nM): 2‐hex‐1‐ynyl‐5′‐N‐ethylcarboxamidoadenosine, 3.9 (1.8–8.4); CGS 21680, 130 (42–405); N6‐cyclohexyladenosine, 9,985 (3,169–31,462). The binding of low concentrations of SCH 58261 was not influenced by either GTP (100 µM) or Mg2+ (10 mM). The present results show that in its tritium‐labeled form, SCH 58261 appears to be a good radioligand for autoradiographic studies, because it does not suffer from some of the problems encountered with the currently used agonist radioligand [3H]CGS 21680.

show abstract

Synthesis of the tritium labeled SCH 58261, a new non-xanthine A2A adenosine receptor antagonist

Cited by 17 publications

References 7 publications

Characterization of human A_2A adenosine receptors with the antagonist radioligand [³H]‐SCH 58261

Characterization of human A_2A adenosine receptors with the antagonist radioligand [³H]‐SCH 58261

Design, Synthesis, and Biological Evaluation of a Second Generation of Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as Potent and Selective A_2A Adenosine Receptor Antagonists

[³H]SCH 58261, a Selective Adenosine A_2A Receptor Antagonist, Is a Useful Ligand in Autoradiographic Studies

Contact Info

Product

Resources

About

Synthesis of the tritium labeled SCH 58261, a new non-xanthine A2A adenosine receptor antagonist

Cited by 17 publications

References 7 publications

Characterization of human A2A adenosine receptors with the antagonist radioligand [3H]‐SCH 58261

Characterization of human A2A adenosine receptors with the antagonist radioligand [3H]‐SCH 58261

Design, Synthesis, and Biological Evaluation of a Second Generation of Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as Potent and Selective A2A Adenosine Receptor Antagonists

[3H]SCH 58261, a Selective Adenosine A2A Receptor Antagonist, Is a Useful Ligand in Autoradiographic Studies

Contact Info

Product

Resources

About

Characterization of human A_2A adenosine receptors with the antagonist radioligand [³H]‐SCH 58261

Characterization of human A_2A adenosine receptors with the antagonist radioligand [³H]‐SCH 58261

Design, Synthesis, and Biological Evaluation of a Second Generation of Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as Potent and Selective A_2A Adenosine Receptor Antagonists

[³H]SCH 58261, a Selective Adenosine A_2A Receptor Antagonist, Is a Useful Ligand in Autoradiographic Studies