Development of an Affinity Ligand for Purification of α2-Adrenoceptors from Human Platelet Membranes

R. M. DeMarinis; A. J. Krog; D. H. Shah; J. Lafferty; K. G. Holden; J. P. Hieble; W. D. Matthews; J. W. Regan; R. J. Lefkowitz; M. G. Caron

doi:10.1021/jm00373a018

Development of an Affinity Ligand for Purification of α₂-Adrenoceptors from Human Platelet Membranes

R. M. DeMarinis
, A. J. Krog
, D. H. Shah
, J. Lafferty
, K. G. Holden
, J. P. Hieble
, W. D. Matthews
, J. W. Regan
, R. J. Lefkowitz
, M. G. Caron

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Human platelets contain α₂-adrenoceptors which are negatively coupled to the enzyme adenylate cyclase. In order to better understand the interaction of this subtype of α receptor with this key enzyme, we have initiated a program to isolate and characterize the a2-adrenoceptor. This report describes the synthesis and biological characterization of a series of molecules that were prepared as affinity ligands for this purpose. The best of these is 9-(allyloxy)-6-chloro-3-methyl-2, 3,4, 5-tetrahydro-1H-3-benzazepine (SK&F 101253). This compound is an α₂-adrenoceptor antagonist, which was obtained by synthetic modification of 6-chloro-3-methyl-2, 3,4, 5-tetrahydro-lH-3-benzazepine (SK&F 86466), a novel antagonist with high affinity for the α₂-receptor.

Original language	English (US)
Pages (from-to)	918-921
Number of pages	4
Journal	Journal of Medicinal Chemistry
Volume	27
Issue number	7
DOIs	https://doi.org/10.1021/jm00373a018
State	Published - Oct 1984
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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@article{794def465e534d67a3d1bac81812d750,

title = "Development of an Affinity Ligand for Purification of α2-Adrenoceptors from Human Platelet Membranes",

abstract = "Human platelets contain α2-adrenoceptors which are negatively coupled to the enzyme adenylate cyclase. In order to better understand the interaction of this subtype of α receptor with this key enzyme, we have initiated a program to isolate and characterize the a2-adrenoceptor. This report describes the synthesis and biological characterization of a series of molecules that were prepared as affinity ligands for this purpose. The best of these is 9-(allyloxy)-6-chloro-3-methyl-2, 3,4, 5-tetrahydro-1H-3-benzazepine (SK\&F 101253). This compound is an α2-adrenoceptor antagonist, which was obtained by synthetic modification of 6-chloro-3-methyl-2, 3,4, 5-tetrahydro-lH-3-benzazepine (SK\&F 86466), a novel antagonist with high affinity for the α2-receptor.",

author = "DeMarinis, \{R. M.\} and Krog, \{A. J.\} and Shah, \{D. H.\} and J. Lafferty and Holden, \{K. G.\} and Hieble, \{J. P.\} and Matthews, \{W. D.\} and Regan, \{J. W.\} and Lefkowitz, \{R. J.\} and Caron, \{M. G.\}",

year = "1984",

month = oct,

doi = "10.1021/jm00373a018",

language = "English (US)",

volume = "27",

pages = "918--921",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "7",

}

TY - JOUR

T1 - Development of an Affinity Ligand for Purification of α2-Adrenoceptors from Human Platelet Membranes

AU - DeMarinis, R. M.

AU - Krog, A. J.

AU - Shah, D. H.

AU - Lafferty, J.

AU - Holden, K. G.

AU - Hieble, J. P.

AU - Matthews, W. D.

AU - Regan, J. W.

AU - Lefkowitz, R. J.

AU - Caron, M. G.

PY - 1984/10

Y1 - 1984/10

N2 - Human platelets contain α2-adrenoceptors which are negatively coupled to the enzyme adenylate cyclase. In order to better understand the interaction of this subtype of α receptor with this key enzyme, we have initiated a program to isolate and characterize the a2-adrenoceptor. This report describes the synthesis and biological characterization of a series of molecules that were prepared as affinity ligands for this purpose. The best of these is 9-(allyloxy)-6-chloro-3-methyl-2, 3,4, 5-tetrahydro-1H-3-benzazepine (SK&F 101253). This compound is an α2-adrenoceptor antagonist, which was obtained by synthetic modification of 6-chloro-3-methyl-2, 3,4, 5-tetrahydro-lH-3-benzazepine (SK&F 86466), a novel antagonist with high affinity for the α2-receptor.

AB - Human platelets contain α2-adrenoceptors which are negatively coupled to the enzyme adenylate cyclase. In order to better understand the interaction of this subtype of α receptor with this key enzyme, we have initiated a program to isolate and characterize the a2-adrenoceptor. This report describes the synthesis and biological characterization of a series of molecules that were prepared as affinity ligands for this purpose. The best of these is 9-(allyloxy)-6-chloro-3-methyl-2, 3,4, 5-tetrahydro-1H-3-benzazepine (SK&F 101253). This compound is an α2-adrenoceptor antagonist, which was obtained by synthetic modification of 6-chloro-3-methyl-2, 3,4, 5-tetrahydro-lH-3-benzazepine (SK&F 86466), a novel antagonist with high affinity for the α2-receptor.

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SN - 0022-2623

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EP - 921

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 7

ER -

Development of an Affinity Ligand for Purification of α₂-Adrenoceptors from Human Platelet Membranes

Abstract

ASJC Scopus subject areas

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