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- W2041337283 abstract "A para substitution pattern of the phenyl ring is a characteristic feature of the first reported selective AT2 receptor agonist M024/C21 (1) and all the nonpeptidic AT2 receptor agonists described so far. Two series of compounds structurally related to 1 but with a meta substitution pattern have now been synthesized and biologically evaluated for their affinity to the AT1 and AT2 receptors. A high AT2/AT1 receptor selectivity was obtained with all 41 compounds synthesized, and the majority exhibited Ki ranging from 2 to 100 nM. Five compounds were evaluated for their functional activity at the AT2 receptor, applying a neurite outgrowth assay in NG108-15 cells. Notably, four of the five compounds, with representatives from both series, acted as potent AT2 receptor antagonists. These compounds were found to be considerably more effective than PD 123,319, the standard AT2 receptor antagonist used in most laboratories. No AT2 receptor antagonists were previously reported among the derivatives with a para substitution pattern. Hence, by a minor modification of the agonist 1 it could be transformed into the antagonist, compound 38. These compounds should serve as valuable tools in the assessment of the role of the AT2 receptor in more complex physiological models." @default.
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- W2041337283 date "2012-02-22" @default.
- W2041337283 modified "2023-09-25" @default.
- W2041337283 title "From the First Selective Non-Peptide AT<sub>2</sub> Receptor Agonist to Structurally Related Antagonists" @default.
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- W2041337283 doi "https://doi.org/10.1021/jm2015099" @default.
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