Abstract
Two benzazaborinine analogues of propranolol were synthesized and extensively profiled in vitro and in vivo. These analogues showed potency and physicochemical and in vitro ADME-tox profiles comparable to propranolol. In addition, both benzazaborinine analogues showed excellent bioavailability and brain penetration following subcutaneous administration in a pharmacokinetic study in rats. These studies unveil the potential of aromatic azaborinines as bioisosteric replacements of naphthalene in drug discovery programs.
MeSH terms
-
Adrenergic beta-Antagonists / chemistry*
-
Adrenergic beta-Antagonists / pharmacokinetics
-
Adrenergic beta-Antagonists / pharmacology
-
Animals
-
Aza Compounds / chemistry*
-
Aza Compounds / pharmacokinetics
-
Aza Compounds / pharmacology
-
Benzene Derivatives / chemistry*
-
Benzene Derivatives / pharmacokinetics
-
Benzene Derivatives / pharmacology
-
Biological Availability
-
Borinic Acids / chemistry*
-
Borinic Acids / pharmacokinetics
-
Borinic Acids / pharmacology
-
Brain / metabolism
-
CHO Cells
-
Cell Line
-
Cricetulus
-
Drug Design
-
Drug Stability
-
Humans
-
Mice
-
Models, Molecular
-
Propranolol / analogs & derivatives*
-
Rats
Substances
-
Adrenergic beta-Antagonists
-
Aza Compounds
-
Benzene Derivatives
-
Borinic Acids
-
Propranolol