17811-62-0Relevant academic research and scientific papers
Iminodiacetic Acid as a Novel Metal-Binding Pharmacophore for New Delhi Metallo-β-lactamase Inhibitor Development
Chen, Allie Y.,Thomas, Caitlyn A.,Thomas, Pei W.,Yang, Kundi,Cheng, Zishuo,Fast, Walter,Crowder, Michael W.,Cohen, Seth M.
, p. 1272 - 1282 (2020/05/25)
The fungal natural product aspergillomarasmine A (AMA) has been identified as a noncompetitive inhibitor of New Delhi metallo-β-lactamase-1 (NDM-1) that inhibits by removing ZnII from the active-site. The nonselective metal-chelating properties and difficult synthesis and derivatization of AMA have hindered the development of this scaffold into a potent and selective inhibitor of NDM-1. Iminodiacetic acid (IDA) has been identified as the metal-binding pharmacophore (MBP) core of AMA that can be leveraged for inhibitor development. Herein, we report the use of IDA for fragment-based drug discovery (FBDD) of NDM-1 inhibitors. IDA (IC50=120 μM) was developed into inhibitor 23 f (IC50=8.6 μM, Ki=2.6 μM), which formed a ternary complex with NDM-1, as evidenced by protein thermal-shift and native-state electrospray ionization mass spectrometry (ESI-MS) experiments. Combining mechanistic analysis with inhibitor derivatization, the use of IDA as an alternative AMA scaffold for NDM-1 inhibitor development is detailed.
Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for imaging of unstable atherosclerotic plaques
Hakimzadeh, Nazanin,Pinas, Victorine A.,Molenaar, Ger,De Waard, Vivian,Lutgens, Esther,Van Eck-Smit, Berthe L. F.,De Bruin, Kora,Piek, Jan J.,Eersels, Jos L. H.,Booij, Jan,Verberne, Hein J.,Windhorst, Albert D.
, (2017/12/08)
Molecular imaging of matrix metalloproteinases (MMPs) may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9) with high selectivity and
New Heterocyclic Product Space for the Castagnoli-Cushman Three-Component Reaction
Dar'In, Dmitry,Bakulina, Olga,Chizhova, Maria,Krasavin, Mikhail
supporting information, p. 3930 - 3933 (2015/08/18)
Significant expansion of heterocyclic product space accessible by the Castagnoli-Cushman reaction (CCR) has been achieved via the use of glutaric anhydride analogues containing endocyclic substitutions with oxygen, nitrogen, and sulfur. Incorporation of these heteroatoms in the anhydride's backbone results in enhanced reactivity and generally lower temperatures that are required for the reactions to go to completion. These findings are particularly significant in light of the CCR recently recognized as an efficient tool for lead-oriented synthesis.
Sulphonamide-based small molecule VLA-4 antagonists
Stasiak, Marcin,Mehlin, Christopher,Boni, Erica,Vaisar, Tomas,Little, Thomas,Kim, Hwa-Ok,Qabar, Maher
, p. 3875 - 3878 (2007/10/03)
The discovery of a sulphonamide by-product with VLA-4 antagonistic activity led to a series of potent, small molecule VLA-4 antagonists. Synthesis, SAR and in vivo evaluation of the selected compound will be presented.
