alpha.2-Adrenergic agonists/antagonists: the synthesis and structure-activity relationships of a series of indolin-2-yl and tetrahydroquinolin-2-yl imidazolines
| Autor: | Susan J. Ward, Marla J. Silbernagel, Daniel Luttinger, Mark H. Perrone, Dean R. Haubrich, Dennis J. Hlasta |
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| Rok vydání: | 1987 |
| Předmět: |
Male
Agonist Indoles Stereochemistry medicine.drug_class Pain Imidazoline receptor Alpha (ethology) Clonidine Mice Structure-Activity Relationship chemistry.chemical_compound Vas Deferens Drug Discovery medicine Animals Adrenergic alpha-Antagonists Chemistry Imidazoles Antagonist Brain Nociceptors Biological activity Prazosin Rats Indoline Quinolines Molecular Medicine Adrenergic alpha-Agonists Idazoxan medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 30:1555-1562 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00392a005 |
| Popis: | The synthesis and alpha 2-adrenergic activity of a series of indolin-2-yl and tetrahydroquinolin-2-yl imidazolines are described. The indolin-2-yl imidazoline 4b was found to possess potent alpha 2-adrenergic agonist and antagonist activity. The modification of the substituents on the indoline ring of 4b has led to the separation of these activities. Substitution on the aromatic ring of 4b with halogen or increasing the size of the N-alkyl substituent of 4b gave alpha 2-adrenergic antagonists without agonist activity. The N-allylindoline 4d is more potent than idazoxan in vitro and is equipotent in vivo, but is less receptor selective (alpha 2 vs. alpha 1) than idazoxan. The cis-1,3-dimethylindolin-2-yl imidazoline 6a is an alpha 2-adrenergic agonist equal in potency to clonidine in vitro, while the trans-1,3-dimethylindolin-2-yl imidazoline 6b is a moderately potent alpha 2-adrenergic antagonist. |
| Databáze: | OpenAIRE |
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