Drug design via pharmacophore identification. Dopaminergic activity of 3H-benz[e]indol-8-amines and their mode of interaction with the dopamine receptor

Journal of Medicinal Chemistry
1986.0

Abstract

The design and synthesis of a series of 3H-benz[e]indol-8-amines are described. Two of the compounds are potent, orally active dopaminergic agents as established by their ability to induce contralateral turning in rats with unilateral 6-hydroxydopamine-induced lesions of the nigrostriatal pathway, to induce ambulation in rats rendered akinetic by bilateral injections of 6-hydroxydopamine into the anterolateral hypothalamus, and to antagonize reserpine-induced catalepsy in mice. The dopamine agonist activity of the 3H-benz[e]indol-8-amines establishes that a pyrrolo ring and a phenolic hydroxyl group can interact similarly with the dopamine receptor and provides evidence for the existence of a hydrogen-bond acceptor nucleus on the dopamine receptor macromolecule that is involved in the behavioral manifestations of dopamine agonists.

Knowledge Graph

Similar Paper

Drug design via pharmacophore identification. Dopaminergic activity of 3H-benz[e]indol-8-amines and their mode of interaction with the dopamine receptor
Journal of Medicinal Chemistry 1986.0
Resorcinol congeners of dopamine derived from benzocycloheptene and indan
Journal of Medicinal Chemistry 1984.0
Synthesis, Resolution, and Preliminary Evaluation of trans-2-Amino-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H-indenes and Related Derivatives as Dopamine Receptors Ligands
Journal of Medicinal Chemistry 1996.0
3-Phenylpiperidines. Central dopamine-autoreceptor stimulating activity
Journal of Medicinal Chemistry 1981.0
Dopaminergic activity of substituted 6-chloro-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines
Journal of Medicinal Chemistry 1982.0
Further Definition of the D<sub>1</sub> Dopamine Receptor Pharmacophore:  Synthesis of trans-6,6a,7,8,9,13b-Hexahydro-5H-benzo[d]naphth[2,1-b]azepines as Rigid Analogues of β-Phenyldopamine
Journal of Medicinal Chemistry 1997.0
Structure–Activity Relationship Study ofN<sup>6</sup>-(2-(4-(1H-Indol-5-yl)piperazin-1-yl)ethyl)-N<sup>6</sup>-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine Analogues: Development of Highly Selective D3 Dopamine Receptor Agonists along with a Highly Potent D2/D3 Agonist and Their Pharmacological Characterization
Journal of Medicinal Chemistry 2012.0
Facile synthesis of octahydrobenzo[h]isoquinolines: Novel and highly potent D1 dopamine agonists
Bioorganic &amp; Medicinal Chemistry 2010.0
Absolute stereochemistry and dopaminergic activity of enantiomers of 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
Journal of Medicinal Chemistry 1982.0
6-(Phenylthio)-substituted 2,3,4,5-tetrahydro-1H-3-benzazepines, a novel class of dopamine receptor antagonists and neuroleptics
Journal of Medicinal Chemistry 1980.0