In vitro pharmacologic activity of congener derivatives and model conjugates of propranolol and practolol

Khan, Mohammad Saghir; Marr-Leisy, D.; Rosenkranz, Roberto P.; Huffman, Brian B.; Verlander, Michael S.; Goodman, Murray; Melmon, Kenneth L.

doi:10.1016/0006-2952(87)90147-x

Cited by 4 publications

(1 citation statement)

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“…In the late 1970s, Murray Goodman and co-workers at the University of California, San Diego, derivatized β-adrenergic receptor agonists and other biogenic amines for attachment to peptides as drug carriers , . Isoproterenol 10 (Figure ) was the first analogue of a biogenic amine (norepinephrine 9 ) successfully derivatized this way.…”

Section: Biogenic Amine Receptor Ligands and Origins Of The Functiona...mentioning

confidence: 99%

Functionalized Congener Approach to the Design of Ligands for G Protein-Coupled Receptors (GPCRs)

Jacobson

2009

Bioconjugate Chem.

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Functionalized congeners, in which a chemically functionalized chain is incorporated at an insensitive site on a pharmacophore, have been designed from the agonist and antagonist ligands of various G protein-coupled receptors (GPCRs). These chain extensions enable a conjugation strategy for detecting and characterizing GPCR structure and function and pharmacological modulation. The focus in many studies of functionalized congeners has been on two families of GPCRs: those responding to extracellular purines and pyrimidines-i.e., adenosine receptors (ARs) and P2Y nucleotide receptors. Functionalized congeners of small-molecule as ligands for other GPCRs and non-G protein coupled receptors have also been designed. For example, among biogenic amine neurotransmitter receptors, muscarinic acetylcholine receptor antagonists and adrenergic receptor ligands have been studied with a functionalized congener approach. Adenosine A 1 , A 2A , and A 3 receptor functionalized congeners have yielded macromolecular conjugates, irreversibly binding AR ligands for receptor inactivation and crosslinking, radioactive probes that use prosthetic groups, immobilized ligands for affinity chromatography, and dual-acting ligands that function as binary drugs. Poly(amidoamine) dendrimers have served as nanocarriers for covalently conjugated AR functionalized congeners. Rational methods of ligand design derived from molecular modeling and templates have been included in these studies. Thus, the design of novel ligands, both small molecules and macromolecular conjugates, for studying the chemical and biological properties of GPCRs have been developed with this approach, has provided researchers with a strategy that is more versatile than the classical medicinal chemical approaches.

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Section: Biogenic Amine Receptor Ligands and Origins Of The Functiona...mentioning

confidence: 99%