PMID: 2522990Apr 1, 1989Paper

Topography and conformational preferences of 6,7,8,9-tetrahydro-1-hydroxy-N,N-dipropyl-5H-benzocyclohepten-6- ylamin e. A rationale for the dopaminergic inactivity

Journal of Medicinal Chemistry
A KarlénU Hacksell


In an attempt to rationalize the inability of phenolic benzocycloheptenylamines to activate dopamine (DA) D2 receptors, we have studied the conformational preferences and topography of 6,7,8,9-tetrahydro-1-hydroxy-N,N-dipropyl-5H-benzocyclohepten-6-++ +ylamine (1). Preferred conformations of 1 have been defined by use of experimental (NMR spectroscopic studies) and theoretical (MMP2, AM1, and MNDO calculations) methods. Topographical characteristics were studied by use of molecular graphics. Results from the MMP2 calculations agree with those from the AM1 calculations and the NMR spectroscopic study--1 seems to preferentially adopt chair conformations with a pseudoequatorial C6 substituent. The MNDO calculations, however, produced results that deviate considerably from those of the other theoretical methods. Most likely, pharmacophore conformations of (S)-1 do not present volumes that are part of the DA D2 receptor essential volume. Therefore, it appears that the energy penalty paid by the pharmacophore conformations is responsible for the dopaminergic inactivity of (S)-1. The inactivity of (R)-1 may be due to high energies of pharmacophore conformations and/or to steric factors since these conformations produce large excess vo...Continue Reading

Related Concepts

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Hereditary Sensory Autonomic Neuropathy

Hereditary Sensory Autonomic Neuropathies are a group of inherited neurodegenerative disorders characterized clinically by loss of sensation and autonomic dysfunction. Here is the latest research on these neuropathies.

Glut1 Deficiency

Glut1 deficiency, an autosomal dominant, genetic metabolic disorder associated with a deficiency of GLUT1, the protein that transports glucose across the blood brain barrier, is characterized by mental and motor developmental delays and infantile seizures. Follow the latest research on Glut1 deficiency with this feed.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Nodding Syndrome

Nodding Syndrome is a neurological and epileptiform disorder characterized by psychomotor, mental, and growth retardation. Discover the latest research on Nodding Syndrome here.

LRRK2 & Microtubules

Mutations in the LRRK2 gene are risk-factors for developing Parkinson’s disease (PD). LRRK2 mutations in PD have been shown to enhance its association with microtubules. Here is the latest research.