Synthesis and bioactivity of propranolol analogues with a rigid skeleton. I.
The synthesis of two kinds of propranolol analogues, A and B, with a rigid skeleton was investigated. The compounds were designed to help identify the conformation involved in beta-adrenergic receptor-propranolol interaction. The key intermediate, 2-hydroxy.2,3-dihydronaphtho[1,8-bc]pyran (5), was obtained starting from acenaphthenone (1). On sequential dehydration, hydroboration, and oxidation, 5 gave 2,3-dihydronaphtho[1,8-bc]pyran-3-one (8), which was converted to compound A. Compound 5 was also derived to 2-formyl-2,3-dihydronaphtho[1,8-bc]pyran (13) via the 2-vinyl compound (12). Condensation of nitromethane with 13 followed by reduction and alkylation produced the desired compound B. The beta-blocking activities of A and B were examined.
Miki
Y
Y
Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Japan.
Hachiken
H
H
Noguchi
K
K
Ohta
M
M
Nakano
A
A
Takahashi
K
K
Takemura
S
S
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis; D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008968:Molecular Conformation; D009200:Myocardial Contraction / Q000187:drug effects; D011433:Propranolol / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D011433:Propranolol