Benzazaborinines as Novel Bioisosteric Replacements of Naphthalene: Propranolol as an Example

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.