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 b...
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| Veröffentlicht in: | Journal of medicinal chemistry 2015-12, Vol.58 (23), p.9287-9295 |
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| container_end_page | 9295 |
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| container_issue | 23 |
| container_start_page | 9287 |
| container_title | Journal of medicinal chemistry |
| container_volume | 58 |
| creator | Rombouts, Frederik J. R Tovar, Fulgencio Austin, Nigel Tresadern, Gary Trabanco, Andrés A |
| description | 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. |
| doi_str_mv | 10.1021/acs.jmedchem.5b01088 |
| format | Article |
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| ispartof | Journal of medicinal chemistry, 2015-12, Vol.58 (23), p.9287-9295 |
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| source | ACS Publications; MEDLINE |
| subjects | 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 Cell Line CHO Cells Cricetulus Drug Design Drug Stability Humans Mice Models, Molecular Propranolol - analogs & derivatives Rats |
| title | Benzazaborinines as Novel Bioisosteric Replacements of Naphthalene: Propranolol as an Example |
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