1332367-79-9

Upstream product

• 3412-76-8 N,N'-dibenzylethylenediamine dihydrochloride 
• 146462-25-1 methyl 6-(bromomethyl)picolinate 
• 104-71-2 N,N'-bis(benzyliden)ethylendiamine 
• 5453-67-8 2,6-bis(methoxycarbonyl)pyridine 
• 100-52-7 benzaldehyde 
• 140-28-3 N,N'-Dibenzylethylenediamine 
• 39977-44-1 methyl 6-(hydroxymethyl)pyridine-2-carboxylate 

Downstream Products

• 1332367-80-2 6,6'-((ethane-1,2-diylbis(benzylazanediyl))bis(methylene))dipicolinic acid 

Relevant academic research and scientific papers

Rapid Thermodynamically Stable Complex Formation of [nat/111In]In3+, [nat/90Y]Y3+, and [nat/177Lu]Lu3+ with H6dappa

A phosphinate-bearing picolinic acid-based chelating ligand (H6dappa) was synthesized and characterized to assess its potential as a bifunctional chelator (BFC) for inorganic radiopharmaceuticals. Nuclear magnetic resonance (NMR) spectroscopy was employed to investigate the chelator coordination chemistry with a variety of nonradioactive trivalent metal ions (In3+, Lu3+, Y3+, Sc3+, La3+, Bi3+). Density functional theory (DFT) calculations explored the coordination environments of aforementioned metal complexes. The thermodynamic stability of H6dappa with four metal ions (In3+, Lu3+, Y3+, Sc3+) was deeply investigated via potentiometric and spectrophotometric (UV-vis) titrations, employing a combination of acidic in-batch, joint potentiometric/spectrophotometric, and ligand-ligand competition titrations; high stability constants and pM values were calculated for all four metal complexes. Radiolabeling conditions for three clinically relevant radiometal ions were optimized ([111In]In3+, [177Lu]Lu3+, [90Y]Y3+), and the serum stability of [111In][In(dappa)]3- was studied. Through concentration-, time-, temperature-, and pH-dependent labeling experiments, it was determined that H6dappa radiolabels most effectively at near-physiological pH for all radiometal ions. Furthermore, very rapid radiolabeling at ambient temperature was observed, as maximal radiolabeling was achieved in less than 1 min. Molar activities of 29.8 GBq/μmol and 28.2 GBq/μmol were achieved for [111In]In3+ and [177Lu]Lu3+, respectively. For H6dappa, high thermodynamic stability did not correlate with kinetic inertness-lability was observed in serum stability studies, suggesting that its metal complexes might not be suitable as a BFC in radiopharmaceuticals.

Systematic research of H2dedpa derivatives as potent inhibitors of New Delhi Metallo-β-lactamase-1

New Delhi Metallo-β-lactamase-1 (NDM-1), a Zn (II)-dependent enzyme, can catalyze the hydrolysis of almost all β-lactam antibiotics including carbapenems, resulting in bacterial antibiotic resistance, which threatens public health globally. Based on our finding that H2dedpa is as an efficient NDM-1 inhibitor, a series of H2dedpa derivatives was systematically prepared. These compounds exhibited significant activity against NDM-1, with IC50 values 0.06–0.94 μM. In vitro, compounds 6k and 6n could restore the activity of meropenem against Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis possessing either NDM or IMP. In particular, the activity of meropenem against E. coli producing NDM-4 could be improved up to 5333 times when these two compounds were used. Time–kill cell-based assays showed that 99.9% of P. mirabilis were killed when treated with meropenem in combination with compound 6k or 6n. Furthermore, compounds 6k and 6n were nonhemolytic (HC50 > 1280 μg/mL) and showed low toxicity toward mammalian (HeLa) cells. Mechanistic studies indicated that compounds 6k and 6n inhibit NDM-1 by chelating the Zn2+ ion of the enzyme.

BIFUNCTIONAL CHELATING AGENTS

A bifunctional chelating agent of the formula (I): wherein the variables R1, R1 , Q1, Q2 and M are as defined in the description of the present application. Also described is a complex of the above chelating age