Medicinal Chemistry Profiling of Monocyclic 1,2‐Azaborines

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...

Full description

Saved in:
Bibliographic Details
Published in:ChemMedChem 2017-03, Vol.12 (5), p.358-361
Main Authors: Zhao, Peng, Nettleton, David O., Karki, Rajeshri G., Zécri, Frédéric J., Liu, Shih‐Yuan
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
azaborines
Binding Sites
BN heterocycle
Boron Compounds - chemistry
Boron Compounds - metabolism
Boron Compounds - pharmacokinetics
CDK2 inhibitors
Chemistry, Pharmaceutical
Cyclin-Dependent Kinase 2 - antagonists & inhibitors
Cyclin-Dependent Kinase 2 - metabolism
drug discovery
Half-Life
Hydrogen Bonding
Male
Molecular Dynamics Simulation
Pharmaceutical industry
Protein Kinase Inhibitors - chemistry
Protein Kinase Inhibitors - metabolism
Protein Structure, Tertiary
Rats
Rats, Sprague-Dawley
Solubility
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. BOR‐ing? NO! Monocyclic 1,2‐azaborines can serve as a novel pharmacophore with improved in vitro aqueous solubility, improved bioactivity, and better in vivo oral availability than their carbonaceous analogues.
ISSN:1860-7179
1860-7187
DOI:10.1002/cmdc.201700047