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. 2017 Mar 7;12(5):358-361.
doi: 10.1002/cmdc.201700047. Epub 2017 Feb 21.

Medicinal Chemistry Profiling of Monocyclic 1,2-Azaborines

Peng Zhao  1 , David O Nettleton  2 , Rajeshri G Karki  2 , Frédéric J Zécri  2 , Shih-Yuan Liu  1
Affiliations

Medicinal Chemistry Profiling of Monocyclic 1,2-Azaborines

Peng Zhao et al. ChemMedChem. .

Abstract

The first examples of biologically active monocyclic 1,2-azaborines have been synthesized and demonstrated to exhibit not only improved in vitro aqueous solubility in comparison with their corresponding carbonaceous analogues, but in the context of a CDK2 inhibitor, also improved biological activity and better in vivo oral bioavailability. This proof-of-concept study establishes the viability of monocyclic 1,2-azaborines as a novel pharmacophore with distinct pharmacological profiles that can help address challenges associated with solubility in drug development research.

Keywords: BN heterocycle; CDK2 inhibitors; azaborines; drug discovery; solubility.

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Figures

Figure 1
Figure 1
Modeled binding mode of BN-3 (green) in the ATP binding site of CDK2 (white). Hydrogen bonding interactions are shown as black dotted lines. Boron in BN-3 is in magenta color.
Scheme 1
Scheme 1
BN/CC isosterism in the context of biologically active biphenyl carboxamides.
Scheme 2
Scheme 2
Effect of BN/CC isosterism on biological activity. Numbers are IC50 values.
See this image and copyright information in PMC

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