title: Benzazaborinines as Novel Bioisosteric Replacements of Naphthalene: Propranolol as an Example.
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.
authors.affiliation: Neuroscience-Medicinal Chemistry, Janssen Research & Development, Janssen Pharmaceutica N.V. , Turnhoutseweg 30, B-2340 Beerse, Belgium.
authors.forename: Frederik J R
authors.initials: FJ
authors.lastname: Rombouts
authors.affiliation: Villapharma Research S.L. , Parque Tecnológico de Fuente Álamo. Ctra. El Estrecho-Lobosillo, Km. 2.5- Av. Azul 30320 Fuente Álamo de Murcia, Murcia, Spain.
authors.forename: Fulgencio
authors.initials: F
authors.lastname: Tovar
authors.affiliation: Discovery Sciences, Janssen Research & Development, Janssen Pharmaceutica N.V. , Turnhoutseweg 30, B-2340 Beerse, Belgium.
authors.forename: Nigel
authors.initials: N
authors.lastname: Austin
authors.forename: Gary
authors.initials: G
authors.lastname: Tresadern
authors.forename: Andrés A
authors.initials: AA
authors.lastname: Trabanco
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001372:Aza Compounds / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D001555:Benzene Derivatives / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D001889:Borinic Acids / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D016466:CHO Cells; D002460:Cell Line; D003412:Cricetulus; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D011433:Propranolol / Q000031:analogs & derivatives*; D051381:Rats
chemical_list: D000319:Adrenergic beta-Antagonists; D001372:Aza Compounds; D001555:Benzene Derivatives; D001889:Borinic Acids; D011433:Propranolol