Synthesis and binding to beta-adrenergic receptors of p-aminobenzyl analogues of practolol and atenolol.
The p-aminobenzyl analogues (8a and 8b, respectively) of the cardioselective beta-adrenergic receptor antagonists practolol and atenolol were prepared from the corresponding phenoxymethyloxiranes in 30 and 13% yields, respectively. The dissociation constants for the beta-adrenergic receptor were measured in membrane preparations of rat heart and lung. In membranes from the heart (which contain mostly beta 1-adrenergic receptors), the affinities of the derivatives and parent compounds were similar. By contrast, in membranes from the lung (which contain mostly beta 2-adrenergic receptors), the derivatives were more potent than the parent compounds. Thus, the cardioselectivities of the p-aminobenzyl analogues 8a and 8b were about one-sixth those of the respective parents.
Jones
G S
GS
Section of Medicinal Chemistry, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, MA 02115.
Bylund
D B
DB
Hanson
R N
RN
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000378:metabolism; D000818:Animals; D001262:Atenolol / Q000031:analogs & derivatives*; D008168:Lung / Q000378:metabolism / Q000648:ultrastructure; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D011217:Practolol / Q000031:analogs & derivatives*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D001262:Atenolol; D011217:Practolol