Comparison of the binding affinity of some newly synthesized phenylethanolamine and phenoxypropanolamine compounds at recombinant human β‐ and α1‐adrenoceptor subtypes

  title={Comparison of the binding affinity of some newly synthesized phenylethanolamine and phenoxypropanolamine compounds at recombinant human $\beta$‐ and $\alpha$1‐adrenoceptor subtypes},
  author={Maruf Ahmed and Yoko Hanaoka and T. Kiso and T. Kakita and Y. Ohtsubo and I. Muramatsu and T. Nagatomo},
  journal={Journal of Pharmacy and Pharmacology},
We evaluated six new compounds, SWR‐0065HA ([4‐[2‐[3‐[[(3,4‐dihydro‐4‐oxo‐[1,2,4]‐triazino(4,5‐a)indol)‐lyl]oxy]‐2‐hydroxypropylamino]ethoxy]phenyl]acetic acid methyl ester hydrochloride), SWR‐0098NA ((R*R*‐UE)‐(E)‐[4‐[3‐[(2‐phenyl‐2‐hydroxyethyl)amino]‐1‐butenyl]phenoxy]acetic acid sodium salt), SWR‐0315NA ((E, Z)‐[4[[1‐[2‐[(3‐phenoxy‐2‐hydroxy propyl)]amino]ethyl]‐1‐propenyl]phenoxy]acetic acid sodium), SWR‐0338SA ((E)‐[4‐[5‐[(2‐phenyl‐2‐hydroxyethyl)amino]‐2‐pentene‐3‐yl]phenoxy] acetic acid… Expand


Binding and functional affinity of some newly synthesized phenethylamine and phenoxypropanolamine derivatives for their agonistic activity at recombinant human β3‐adrenoceptor
Thirteen new compounds have been evaluated for their potencies and efficacies asβ3‐adrenoceptor agonists on human β3‐ adrenoceptor expressed in COS‐7 and Chinese hamster ovary (CHO) cells using radio ligand binding assay and cyclic AMP (cAMP) accumulation assay. Expand
Molecular characterization of pharmacological properties and selectivity of SWR-0315NA for beta3-adrenoceptors.
Results indicate that although SWR-0315NA has lower binding selectivity towards beta-AR subtypes, it is a selective agonist with high intrinsic activity for beta(3)-AR as compared with (-)-isoproterenol. Expand
Anti-obesity and anti-diabetic activities of a new beta3 adrenergic receptor agonist, (S)-(Z)-[4-[[1-[2-[(2-hydroxy-3-phenoxypropyl)]amino]ethyl]-1-propenyl] phenoxy] acetic acid ethanedioic acid (SWR-0342SA), in KK-Ay mice.
The results indicated that SWR-0342SA is a selective beta3-AR agonist, and possesses potent anti-di diabetic activity, and that the anti-obesity activity is inferior to theAnti-diabetic activity. Expand
Binding and Functional Affinity of Sarpogrelate, Its Metabolite M-1 and Ketanserin for Human Recombinant Alpha-1-Adrenoceptor Subtypes
The present results indicate that sarpogrelate and M-1 have antagonistic activity to the three α1-AR subtypes, but their affinities are significantly lower than those of ketanserin. Expand
Molecular characterization of pharmacological properties of T-0509 for beta-adrenoceptors.
The results indicate that T-0509 is a relatively specific beta 1-adrenoceptor agonist with a high intrinsic activity as compared with isoproterenol. Expand
Pharmacological subclassification of α1‐adrenoceptors in vascular smooth muscle
1 We examined whether α1‐adrenoceptors in various blood vessels can be divided into subtypes by antagonist affinity or by susceptibility to chloroethylclonidine or nifedipine. 2 Noradrenaline orExpand
Desensitization and resensitization of β1‐ and putative β4‐adrenoceptor mediated responses occur in parallel in a rat model of cardiac failure
It is suggested that CGP 12177A produces its cardiac effects by interacting with a low affinity state of the β1‐ and putative β4‐adrenoceptor use the same signalling pathway. Expand
Beta-adrenoceptors: three-dimensional structures and binding sites for ligands.
This review summarizes current findings on chemical structures of ligands, amino acid sequences, 3D structures and important amino acids of beta-AR subtypes for interacting with ligands obtained from mutagenesis, chimeric studies and molecular modeling techniques. Expand
Overexpression of β1‐adrenoceptors in adult rat ventricular myocytes enhances CGP 12177A cardiostimulation: implications for ‘putative’β4‐adrenoceptor pharmacology
  • Clive J Lewis, H. Gong, Morris J Brown, S. Harding
  • Biology, Medicine
  • British journal of pharmacology
  • 2004
Enhanced cardiostimulation by CGP 12177A (in the presence of propranolol) in rat ventricular myocytes overexpressing β1‐adrenoceptors, mediated by a Gs/cAMP signalling pathway is demonstrated. Expand
A mutation-induced activated state of the beta 2-adrenergic receptor. Extending the ternary complex model.
The experimental findings with the mutant receptor cannot be adequately rationalized within the theoretical framework of the Ternary Complex Model, and an extended version of this model that includes an explicit isomerization of the receptor to an active state closely models all the findings for both the mutant and the wild-type receptors. Expand