In:
Journal of Pharmacy and Pharmacology, Oxford University Press (OUP), Vol. 57, No. 1 ( 2010-02-18), p. 75-81
Abstract:
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 ethanedioic acid), SWR-0342SA ((S)-(Z)-[4-[[1-[2-[(2-hydroxy-3-phenoxypropyl)] amino] ethyl] -1-propenyl]phenoxy] acetic acid ethanedioic acid) and SWR-0345HA ((E)-2-methyl-3-[4-[2-(2-phenyl-2-hydroxyethylamino)ethoxy]phenyl] -2-propenoic acid ethyl ester hydrochloride) for their potencies as selective ligands at human β-adrenoceptors expressed in COS-7 cells and compared the binding affinities for human α1-adrenoceptors expressed in Chinese hamster ovary (CHO) cells using a radioligand-binding assay. Phenoxypropanolamine derivatives SWR-0315NA and SWR-0342SA showed higher binding affinities for β-adrenoceptor subtypes; SWR-0065HA, however, showed a higher affinity for only β2-adrenoceptors, accounting for 3-fold and 6-fold selectivity against β1- and β3-adrenoceptors. Compounds SWR-0315NA and SWR-0342SA did not show any binding selectivity for any of the subtypes. However, functionally these two compounds are selective for β3-adrenoceptors. Among the phenylethanolamine derivatives, SWR-0338SA and SWR-0345HA showed 9-fold and 16-fold higher binding selectivity for β3-adrenoceptors against β1-adrenoceptors, respectively, whereas they both showed a 7-fold higher binding selectivity for β3-adrenoceptors against β2-adrenoceptors. SWR-0098NA did not show any significant binding affinity for any of the β-adrenoceptor subtypes. These compounds, except for SWR-0098NA, were not found to possess any significant binding affinity for α1-adrenoceptor subtypes over that for β-adrenoceptor subtypes. However, SWR-0098NA has about a 3-fold to 22-fold higher binding selectivity for α1-adrenoceptor subtypes against β-adrenoceptor subtypes, making it difficult for use in a β-adrenoceptor receptor study. Compounds SWR-0315NA and SWR-0342SA have similar binding potency for α1-adrenoceptors as adrenaline (epinephrine), proving the finding of this manuscript that this phenoxypropanolamine group of β-adrenoceptor ligands could also be used as α1-adrenoceptor ligands. Functional assays have to be performed to confirm their agonistic activity.
Type of Medium:
Online Resource
ISSN:
0022-3573
,
2042-7158
DOI:
10.1211/0022357055074
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2010
detail.hit.zdb_id:
2041988-0
detail.hit.zdb_id:
2050532-2
SSG:
15,3
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