alpha.-Adrenergic agents. 2. Synthesis and .alpha.1-agonist activity of 2-aminotetralins
| Autor: | D H Shah, R. F. Hall, Robert G. Pendleton, J. P. Hieble, Robert M. DeMarinis |
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| Rok vydání: | 1982 |
| Předmět: |
Agonist
Chemical Phenomena Tetrahydronaphthalenes Stereochemistry medicine.drug_class Substituent Alpha (ethology) Ear Naphthalenes Alpha-1A adrenergic receptor Chemistry Structure-Activity Relationship chemistry.chemical_compound chemistry Drug Discovery medicine Animals Vasoconstrictor Agents Molecular Medicine Structure–activity relationship Potency Rabbits Receptor Adrenergic alpha-Agonists EC50 |
| Zdroj: | Journal of Medicinal Chemistry. 25:136-141 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00344a009 |
| Popis: | Substituted 2-aminotetralins are potent, selective, direct-acting agonists at postjunctional alpha 1 receptors. Within this series, substituent alterations on the ring, as well as on the nitrogen, change the potency of compounds by over three orders of magnitude (EC50 = 12 to greater than 10 000 nM). It has been demonstrated experimentally that substitution at both the 5 and 8 positions of the aromatic ring produces optimum agonist potency. Removal of either substituent results in a loss of potency and efficacy relative to norepinephrine. Substitution at positions 6 and/or 7 is generally detrimental to activity. Methyl, ethyl, or dimethyl substitution on nitrogen is compatible with high agonist potency, while substitution with larger groups is not. The most potent agonist in this series is 5-(thiomethyl)-8-methoxy-2-aminotetralin, which has an EC50 of 12 nM. |
| Databáze: | OpenAIRE |
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