- Title
- A novel structural framework for α1A/D-adrenoceptor selective antagonists identified using subtype selective pharmacophores
- Creator
- Stoddart, Emily S.; Senadheera, Sevvandi; MacDougall, Iain J. A.; Griffith, Renate; Finch, Angela M.
- Relation
- PLoS ONE Vol. 6, Issue 5
- Publisher Link
- http://dx.doi.org/10.1371/journal.pone.0019695
- Publisher
- Public Library of Science
- Resource Type
- journal article
- Date
- 2011
- Description
- In this study four and five-feature pharmacophores for selective antagonists at each of the three α₁-adrenoceptor (AR) subtypes were used to identify novel α₁-AR subtype selective compounds in the National Cancer Institute and Tripos LeadQuest databases. 12 compounds were selected, based on diversity of structure, predicted high affinity and selectivity at the α1D- subtype compared to α1A- and α1B-ARs. 9 out of 12 of the tested compounds displayed affinity at the α1A and α1D -AR subtypes and 6 displayed affinity at all three α₁-AR subtypes, no α1B-AR selective compounds were identified. 8 of the 9 compounds with α₁-AR affinity were antagonists and one compound displayed partial agonist characteristics. This virtual screening has successfully identified an α1A/D-AR selective antagonist, with low µM affinity with a novel structural scaffold of a an isoquinoline fused three-ring system and good lead-like qualities ideal for further drug development.
- Subject
- pharmacophores; antagonists; database searching
- Identifier
- http://hdl.handle.net/1959.13/1042852
- Identifier
- uon:14134
- Identifier
- ISSN:1932-6203
- Language
- eng
- Full Text
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