2,3-Dihydro-2-oxo-1H-benzimidazole-1-carboxamides with Selective Affinity for the 5-HT4Receptor:  Synthesis and Structure−Affinity and Structure−Activity Relationships of a New Series of Partial Agonist and Antagonist Derivatives

1999 ◽  
Vol 42 (15) ◽  
pp. 2870-2880 ◽  
Author(s):  
Inés Tapia ◽  
Luisa Alonso-Cires ◽  
Pedro Luis López-Tudanca ◽  
Ramón Mosquera ◽  
Luis Labeaga ◽  
...  
Keyword(s):  
Partial Agonist ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Agonist And Antagonist

scholarly journals The Discovery of Novel Selective D1 Dopaminergic Agonists: A-68930, A-77636, A-86929, and ABT-413

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Yvonne Connolly Martin
Keyword(s):  
Medicinal Chemistry ◽  
Partial Agonist ◽  
Skf 38393 ◽  
The Novel ◽  
Bioactive Conformation ◽  
Dopaminergic Agonists ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
A 68930

The novel selective D1 dopaminergic full agonists A-68930, A-77636 were discovered by the synthesis of molecules to probe the bioactive conformation of the partial agonist SKF-38393, by the use of this information to add D1 affinity and selectivity to a screening hit, and by traditional medicinal chemistry exploration of structure-activity relationships. The subsequent design of A-86929 and ABT-413 capitalized on these results, recently disclosed agonists, and traditional medicinal chemistry.

Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators: An Update in Structure-Activity Relationships

2018 ◽  
Vol 25 (20) ◽  
pp. 2353-2384 ◽  
Author(s):  
Carlo Mustazza ◽  
Stefano Pieretti ◽  
Francesca Marzoli
Keyword(s):  
Partial Agonist ◽  
Orphanin Fq ◽  
Structure Activity Relationships ◽  
Airway Constriction ◽  
Structure Activity ◽  
Antinociceptive Effects ◽  
Μ Opioid Receptor ◽  
Receptor Modulators ◽  
G Protein Coupled ◽  
Higher Doses

Nociceptin /Orphanin FQ Peptide” receptor (NOPr) is a G-protein-coupled receptor with the nociceptin/orphanin FQ peptide (N/OFQ) as endogenous agonist. It is expressed in the nervous system as well as in some non-neural tissues. Its activation has pronociceptive effect at the supraspinal level, whereas at the spinal level it produces nociceptive effects at low doses and antinociceptive effects at higher doses. NOPr is also involved in mood and blood pressure regulation, immunoregulation, airway constriction, feeding, urination, bowel motility, learning and memory. Selective NOPr agonists have been tested clinically as anxiolytics and antitussives, and the antagonists as analgesics, antidepressants and in the treatment of alcohol addiction. Two NOPr radioligands have also been tested in humans as neuroimaging agents. Furthermore, the partial agonist peptide SER100 and N/OFQ have been used in clinical trials, respectively for congestive heart failure and overactive bladder. The evidence of interactions between NOP and μ-opioid receptor (MOPr) receptors has been exploited in the use of mixed NOPr/MOPr modulators as analgesics and in the treatment of drug addiction. These drugs are devoid of typical opioid liabilities. In this review, we outline the latest advances in the structure-activity relationships (SAR) of NOPr agonists and antagonists, with emphasis on affinity, activity, selectivity and pharmacokinetic features.

scholarly journals Structure–Activity Relationships of 7-Substituted Dimethyltyrosine-Tetrahydroisoquinoline Opioid Peptidomimetics

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4302 ◽  
Author(s):  
Deanna Montgomery ◽  
Jessica P. Anand ◽  
Mason A. Baber ◽  
Jack J. Twarozynski ◽  
Joshua G. Hartman ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Partial Agonist ◽  
Kappa Opioid Receptor ◽  
Structure Activity Relationships ◽  
Opioid Ligands ◽  
Structure Activity ◽  
The Creation ◽  
Agonist Ligands ◽  
Potential Therapeutics

The opioid receptors modulate a variety of biological functions, including pain, mood, and reward. As a result, opioid ligands are being explored as potential therapeutics for a variety of indications. Multifunctional opioid ligands, which act simultaneously at more than one type of opioid receptor, show promise for use in the treatment of addiction, pain, and other conditions. Previously, we reported the creation of bifunctional kappa opioid receptor (KOR) agonist/mu opioid receptor (MOR) partial agonist ligands from the classically delta opioid receptor (DOR) antagonist selective dimethyltyrosine-tetrahydroisoquinoline (Dmt-Tiq) scaffold through the addition of a 7-benzyl pendant on the tetrahydroisoquinoline ring. This study further explores the structure–activity relationships surrounding 7-position pendants on the Dmt-Tiq scaffold. Some analogues maintain a KOR agonist/MOR partial agonist profile, which is being explored in the development of a treatment for cocaine addiction. Others display a MOR agonist/DOR antagonist profile, which has potential to be used in the creation of a less addictive pain medication. Ultimately, we report the synthesis and in vitro evaluation of novel opioid ligands with a variety of multifunctional profiles.

The synthesis, reactivity, and pharmacological properties of some substituted NN -dimethyl-2-halogeno-2-phenylethylamines, and related compounds

1965 ◽  
Vol 163 (990) ◽  
pp. 116-135 ◽  
Keyword(s):  
Receptor Binding ◽  
Phenyl Group ◽  
Hydroxyl Group ◽  
Pharmacological Properties ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Agonist And Antagonist ◽  
The Many ◽  
Related Compounds ◽  
Alcoholic Hydroxyl

With the object of clarifying ideas about the adrenaline α -receptor and antagonism to catecholamines, a series of compounds mentioned in the title, with 3-, 4-, or 3,4-substituents in the phenyl group, has been synthesized; the compounds were isolated as their hydrohalides and subjected to both physicochemical and pharmacological investigations. The anti-adrenaline, anti-noradrenaline, and anti-histamine activities of many of the compounds are reported. Differences in properties of this class of halogenoethylamines from those previously observed of the many members of the ‘Dibenamine' ( NN -dibenzyl-2-chloroethylamine hydrochloride) class are confirmed. Structure-activity relationships for the anti-adrenaline compounds are fully discussed : it is concluded that Belleau’s theory of the adrenaline α -receptor (Belleau 1958), successful as it is in explaining the behaviour of the ‘Dibenamine’ group, is not fully adequate to explain the behaviour of the present compounds. A development of the theory is proposed in which the importance of similar geometry for agonist and antagonist, and of the site in the receptor binding the alcoholic hydroxyl group of the agonist is emphasized. The anti-histamine properties of some of the compounds are briefly considered.

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