The significance of 2-furyl ring substitution with a 2-(para-substituted) aryl group in a new series of pyrazolo-triazolo-pyrimidines as potent and highly selective hA3 adenosine receptors antagonists: new insights into structure-affinity relationship and receptor-antagonist recognition
Among the heterocyclic structures identified as potent human A3 (hA3) adenosine receptor’s antagonists, we have demonstrated that the new pyrazolo-triazolo-pyrimidines, bearing an aryl group in replacement of the C2-furyl ring, not only confer a good pharmacological profile (with significantly enhan...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Journal Article |
| Published: |
ACS Publications
2010
|
| Subjects: | |
| Online Access: | http://hdl.handle.net/20.500.11937/36735 |
| _version_ | 1848754853012045824 |
|---|---|
| author | Cheong, S. Dolzhenko, A. Kachler, S. Paoletta, S. Federico, S. Cacciari, B. Dolzhenko, Anton Klotz, K. Moro, S. Spalluto, G. Pastorin, G. |
| author_facet | Cheong, S. Dolzhenko, A. Kachler, S. Paoletta, S. Federico, S. Cacciari, B. Dolzhenko, Anton Klotz, K. Moro, S. Spalluto, G. Pastorin, G. |
| author_sort | Cheong, S. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Among the heterocyclic structures identified as potent human A3 (hA3) adenosine receptor’s antagonists, we have demonstrated that the new pyrazolo-triazolo-pyrimidines, bearing an aryl group in replacement of the C2-furyl ring, not only confer a good pharmacological profile (with significantly enhanced selectivity against other adenosine receptor subytpes) but also overcome the metabolic transformation of the furan ring into toxic intermediates. All the synthesized [2-(para-substituted) phenyl]-pyrazolo-triazolo-pyrimidines showed affinity at the hA3 receptor in the low nanomolar range. The most potent derivative of the series presented better affinity and excellent selectivity (compound 31, Ki hA3 = 0.108 nM; hA1/hA3 = 5200; hA2A/hA3 = 7200), in comparison to the C2-furyl counterpart. A receptor-driven molecular modeling investigation, based on a recently proposed model of A3 receptor derived from the crystallographic structure of human A2A receptor, has been carried out in order to support the experimental binding data and to justify the enhanced selectivity against the other receptor subtypes |
| first_indexed | 2025-11-14T08:47:00Z |
| format | Journal Article |
| id | curtin-20.500.11937-36735 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:47:00Z |
| publishDate | 2010 |
| publisher | ACS Publications |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-367352017-09-13T16:07:21Z The significance of 2-furyl ring substitution with a 2-(para-substituted) aryl group in a new series of pyrazolo-triazolo-pyrimidines as potent and highly selective hA3 adenosine receptors antagonists: new insights into structure-affinity relationship and receptor-antagonist recognition Cheong, S. Dolzhenko, A. Kachler, S. Paoletta, S. Federico, S. Cacciari, B. Dolzhenko, Anton Klotz, K. Moro, S. Spalluto, G. Pastorin, G. drug-receptor interactions triazoles adenosine receptor antagonists molecular modeling pyrimidines pyrazoles Among the heterocyclic structures identified as potent human A3 (hA3) adenosine receptor’s antagonists, we have demonstrated that the new pyrazolo-triazolo-pyrimidines, bearing an aryl group in replacement of the C2-furyl ring, not only confer a good pharmacological profile (with significantly enhanced selectivity against other adenosine receptor subytpes) but also overcome the metabolic transformation of the furan ring into toxic intermediates. All the synthesized [2-(para-substituted) phenyl]-pyrazolo-triazolo-pyrimidines showed affinity at the hA3 receptor in the low nanomolar range. The most potent derivative of the series presented better affinity and excellent selectivity (compound 31, Ki hA3 = 0.108 nM; hA1/hA3 = 5200; hA2A/hA3 = 7200), in comparison to the C2-furyl counterpart. A receptor-driven molecular modeling investigation, based on a recently proposed model of A3 receptor derived from the crystallographic structure of human A2A receptor, has been carried out in order to support the experimental binding data and to justify the enhanced selectivity against the other receptor subtypes 2010 Journal Article http://hdl.handle.net/20.500.11937/36735 10.1021/jm100049f ACS Publications restricted |
| spellingShingle | drug-receptor interactions triazoles adenosine receptor antagonists molecular modeling pyrimidines pyrazoles Cheong, S. Dolzhenko, A. Kachler, S. Paoletta, S. Federico, S. Cacciari, B. Dolzhenko, Anton Klotz, K. Moro, S. Spalluto, G. Pastorin, G. The significance of 2-furyl ring substitution with a 2-(para-substituted) aryl group in a new series of pyrazolo-triazolo-pyrimidines as potent and highly selective hA3 adenosine receptors antagonists: new insights into structure-affinity relationship and receptor-antagonist recognition |
| title | The significance of 2-furyl ring substitution with a 2-(para-substituted) aryl group in a new series of pyrazolo-triazolo-pyrimidines as potent and highly selective hA3 adenosine receptors antagonists: new insights into structure-affinity relationship and receptor-antagonist recognition |
| title_full | The significance of 2-furyl ring substitution with a 2-(para-substituted) aryl group in a new series of pyrazolo-triazolo-pyrimidines as potent and highly selective hA3 adenosine receptors antagonists: new insights into structure-affinity relationship and receptor-antagonist recognition |
| title_fullStr | The significance of 2-furyl ring substitution with a 2-(para-substituted) aryl group in a new series of pyrazolo-triazolo-pyrimidines as potent and highly selective hA3 adenosine receptors antagonists: new insights into structure-affinity relationship and receptor-antagonist recognition |
| title_full_unstemmed | The significance of 2-furyl ring substitution with a 2-(para-substituted) aryl group in a new series of pyrazolo-triazolo-pyrimidines as potent and highly selective hA3 adenosine receptors antagonists: new insights into structure-affinity relationship and receptor-antagonist recognition |
| title_short | The significance of 2-furyl ring substitution with a 2-(para-substituted) aryl group in a new series of pyrazolo-triazolo-pyrimidines as potent and highly selective hA3 adenosine receptors antagonists: new insights into structure-affinity relationship and receptor-antagonist recognition |
| title_sort | significance of 2-furyl ring substitution with a 2-(para-substituted) aryl group in a new series of pyrazolo-triazolo-pyrimidines as potent and highly selective ha3 adenosine receptors antagonists: new insights into structure-affinity relationship and receptor-antagonist recognition |
| topic | drug-receptor interactions triazoles adenosine receptor antagonists molecular modeling pyrimidines pyrazoles |
| url | http://hdl.handle.net/20.500.11937/36735 |