Synthesis of a selective alpha-2A adrenoceptor antagonist, BRL 48962, and its characterization at cloned human alpha-adrenoceptors.
The chiral synthesis of the potent and selective alpha-2A antagonist, BRL 48962, is described. Evaluation of BRL 48962 at cloned human alpha-adrenoceptors indicates that this antagonist has a selectivity in the order of 30-fold for the alpha-2A subtype.
Beeley
L J
LJ
Department of Medicinal Chemistry, SmithKline Beecham Pharmaceuticals, Great Burgh, Epsom, Surrey, U.K.
Berge
J M
JM
Chapman
H
H
Hieble
P
P
Kelly
J
J
Naselsky
D P
DP
Rockell
C M
CM
Young
P W
PW
D000273:Adipose Tissue / Q000378:metabolism; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D016466:CHO Cells; D002540:Cerebral Cortex / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D054833:Isoindoles; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011817:Rabbits; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D018341:Receptors, Adrenergic, alpha-2; D011994:Recombinant Proteins; C072125:BRL 44408