BIOMAT Database Logo BIOMAT Database Logo

Conformationally defined adrenergic agents. 1. Design and synthesis of novel alpha 2 selective adrenergic agents: electrostatic repulsion based conformational prototypes. 1985

J F DeBernardis, and D J Kerkman, and M Winn, and E N Bush, and D L Arendsen, and W J McClellan, and J J Kyncl, and F Z Basha

A previous report of the adrenergic selectivity of 2- and 6-fluoronorepinephrine prompted us to formulate a hypothesis that accounted for this selectivity on the basis of a conformational preference induced by electrostatic repulsion between the aromatic fluorine atom and the side-chain hydroxyl group. A series of nitrogen-substituted catechol (aminomethyl)benzocyclobutenes, indanes, tetralins, and benzocycloheptenes were prepared, and when their radioligand binding affinities were determined, it was found that the overall pattern of binding affinity results supported the electrostatic repulsion hypothesis. The radioligand binding assay also revealed several highly alpha 2 selective adrenergic agents among these compounds, with the binding selectivity maximizing for compounds having nitrogen substituted with a group no larger than methyl and having a five-membered carbocyclic ring (i.e., 16, 17, and 19).

UI MeSH Term Description Entries
D008297 Male Males
D008968 Molecular Conformation The characteristic three-dimensional shape of a molecule. Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D009038 Motion Physical motion, i.e., a change in position of a body or subject as a result of an external force. It is distinguished from MOVEMENT, a process resulting from biological activity. Motions
D011869 Radioligand Assay Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders). Protein-Binding Radioassay,Radioreceptor Assay,Assay, Radioligand,Assay, Radioreceptor,Assays, Radioligand,Assays, Radioreceptor,Protein Binding Radioassay,Protein-Binding Radioassays,Radioassay, Protein-Binding,Radioassays, Protein-Binding,Radioligand Assays,Radioreceptor Assays
D011942 Receptors, Adrenergic, alpha One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation. Adrenergic alpha-Receptor,Adrenergic alpha-Receptors,Receptors, alpha-Adrenergic,alpha-Adrenergic Receptor,alpha-Adrenergic Receptors,Receptor, Adrenergic, alpha,Adrenergic alpha Receptor,Adrenergic alpha Receptors,Receptor, alpha-Adrenergic,Receptors, alpha Adrenergic,alpha Adrenergic Receptor,alpha Adrenergic Receptors,alpha-Receptor, Adrenergic,alpha-Receptors, Adrenergic
D002627 Chemistry, Physical The study of CHEMICAL PHENOMENA and processes in terms of the underlying PHYSICAL PHENOMENA and processes. Physical Chemistry,Chemistries, Physical,Physical Chemistries
D004560 Electricity The physical effects involving the presence of electric charges at rest and in motion.
D000316 Adrenergic alpha-Agonists Drugs that selectively bind to and activate alpha adrenergic receptors. Adrenergic alpha-Receptor Agonists,alpha-Adrenergic Receptor Agonists,Adrenergic alpha-Agonist,Adrenergic alpha-Receptor Agonist,Receptor Agonists, Adrenergic alpha,Receptor Agonists, alpha-Adrenergic,alpha-Adrenergic Agonist,alpha-Adrenergic Agonists,alpha-Adrenergic Receptor Agonist,Adrenergic alpha Agonist,Adrenergic alpha Agonists,Adrenergic alpha Receptor Agonist,Adrenergic alpha Receptor Agonists,Agonist, Adrenergic alpha-Receptor,Agonist, alpha-Adrenergic,Agonist, alpha-Adrenergic Receptor,Agonists, Adrenergic alpha-Receptor,Agonists, alpha-Adrenergic,Agonists, alpha-Adrenergic Receptor,Receptor Agonist, alpha-Adrenergic,Receptor Agonists, alpha Adrenergic,alpha Adrenergic Agonist,alpha Adrenergic Agonists,alpha Adrenergic Receptor Agonist,alpha Adrenergic Receptor Agonists,alpha-Agonist, Adrenergic,alpha-Agonists, Adrenergic,alpha-Receptor Agonist, Adrenergic,alpha-Receptor Agonists, Adrenergic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

Related Publications

J F DeBernardis, and D J Kerkman, and M Winn, and E N Bush, and D L Arendsen, and W J McClellan, and J J Kyncl, and F Z Basha
2-Amino- and 2-guanidino-1,2,3,4-tetrahydro-1,4-epoxynaphthalenes as conformationally defined analogues of alpha-adrenergic agents.
June 1987, Journal of medicinal chemistry,
J F DeBernardis, and D J Kerkman, and M Winn, and E N Bush, and D L Arendsen, and W J McClellan, and J J Kyncl, and F Z Basha
Conformational preferences of dopamine analogues for inhibition of norepinephrine N-methyltransferase. Conformationally defined adrenergic agents.
September 1982, Life sciences,
J F DeBernardis, and D J Kerkman, and M Winn, and E N Bush, and D L Arendsen, and W J McClellan, and J J Kyncl, and F Z Basha
alpha-Adrenergic agents. 2. Synthesis and alpha 1-agonist activity of 2-aminotetralins.
February 1982, Journal of medicinal chemistry,
J F DeBernardis, and D J Kerkman, and M Winn, and E N Bush, and D L Arendsen, and W J McClellan, and J J Kyncl, and F Z Basha
Conformational preferences of amphetamine analogues for inhibition of phenylethanolamine N-methyltransferase. Conformationally defined adrenergic agents. 5.
September 1981, Molecular pharmacology,
J F DeBernardis, and D J Kerkman, and M Winn, and E N Bush, and D L Arendsen, and W J McClellan, and J J Kyncl, and F Z Basha
Design and synthesis of conformationally constrained hydroxylated 4-phenyl-2-aryl chromenopyridines as novel and selective topoisomerase II-targeted antiproliferative agents.
October 2015, Bioorganic & medicinal chemistry,
J F DeBernardis, and D J Kerkman, and M Winn, and E N Bush, and D L Arendsen, and W J McClellan, and J J Kyncl, and F Z Basha
Medetomidine analogs as alpha 2-adrenergic ligands. 2. Design, synthesis, and biological activity of conformationally restricted naphthalene derivatives of medetomidine.
July 1996, Journal of medicinal chemistry,
J F DeBernardis, and D J Kerkman, and M Winn, and E N Bush, and D L Arendsen, and W J McClellan, and J J Kyncl, and F Z Basha
Conformationally defined adrenergic agents I: potentiation of levarterenol in rat vas deferens by endo- and exo- 2- aminobenzobicyclo[2.2.2]octenes, conformationally defined analogs of amphetamine.
June 1976, Journal of pharmaceutical sciences,
J F DeBernardis, and D J Kerkman, and M Winn, and E N Bush, and D L Arendsen, and W J McClellan, and J J Kyncl, and F Z Basha
Selective alpha 1-adrenergic antagonists: therapeutically relevant antihypertensive agents.
January 1984, The American journal of cardiology,
J F DeBernardis, and D J Kerkman, and M Winn, and E N Bush, and D L Arendsen, and W J McClellan, and J J Kyncl, and F Z Basha
Conformationally defined adrenergic agents. II. The effect of endo- and exo-2-aminobenzobicyclo-[2.2.2] octene, conformationally defined amphetamine analogs, on the uptake and release of central catecholamines.
September 1977, The Journal of pharmacology and experimental therapeutics,
J F DeBernardis, and D J Kerkman, and M Winn, and E N Bush, and D L Arendsen, and W J McClellan, and J J Kyncl, and F Z Basha
Conformationally based design of macrocycles as antitumor agents.
July 2008, Current opinion in drug discovery & development,
Copied contents to your clipboard!