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

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• 作者：Frederik J. R. Rombouts ; Fulgencio Tovar ; Nigel Austin ; Gary Tresadern ; Andr茅s A. Trabanco
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：December 10, 2015
• 年：2015
• 卷：58
• 期：23
• 页码：9287-9295
• 全文大小：367K
• ISSN：1520-4804

文摘

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鈥搕ox 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.