41337-81-9Relevant articles and documents
The effect of pyridinecarboxylate chelating groups on the stability and electronic relaxation of gadolinium complexes
Chatterton, Nicholas,Gateau, Christelle,Mazzanti, Marinella,Pecaut, Jacques,Borel, Alain,Helm, Lothar,Merbach, Andre
, p. 1129 - 1135 (2005)
The ligand N,N′-bis[(6-carboxy-2-pyridylmethyl]ethylenediamine-N, N′-diacetic acid (H4bpeda) was synthesised using an improved procedure which requires a reduced number of steps and leads to a higher yield with respect to the published procedure. It was obtained in three steps from diethylpyridine-2,6-dicarboxylate and commercially available ethylenediamine-N,N′-diacetic acid with a total yield of ～20%. The crystal structure of the hexa-protonated form of the ligand which was determined by X-ray diffraction shows that the four carboxylates and the two amines are protonated. The crystal structure of the polynuclear complex [Gd(bpeda)(H 2O)2]3[Gd(H2O)6] 2Cl3 (2), isolated by slow evaporation of a 1 : 1 mixture of GdCl3 and H4bpeda at pH ～ 1, was determined by X-ray diffraction. In complex 2 three [Gd(bpeda)(H2O)2] units, containing a Gd(III) ion ten-coordinated by the octadentate bpeda and two water molecules, are connected in a pentametallic structure by two hexa-aquo Gd3+ cations through four carboxylato bridges. The protonation constants (pKa1 = 2.9(1), pKa2 = 3.5(1), pKa3 = 5.2(2), and pKa4 = 8.5(1)) and the stability constants of the complexes formed between Gd(III) and Ca(II) ions and H4 bpeda (logβGdL = 15.1(3); logβCaL = 9.4(1)) were determined by potentiometric titration. The unexpected decrease in the stability of the gadolinium complex and of the calcium complex of the octadentate ligand bpeda4- with respect to the hexadentate ligand edta4- has been interpreted in terms of an overall lower contribution to stability of the metal-nitrogen interactions. The EPR spectra display very broad lines (apparent ΔHpp ～800-1200 G at X-band and 90-110 G at Q-band depending on the temperature), indicating a rapid transverse electron spin relaxation. At X-band, Gd(bpeda) is among the fastest relaxing Gd3+ complexes to date suggesting that the presence of pyridinecarboxylate chelating groups in itself does not lead to slow electron relaxation. The Royal Society of Chemistry 2005.
NOVEL 5 OR 8-SUBSTITUTED IMIDAZO [1, 5-a] PYRIDINES AS INDOLEAMINE AND/OR TRYPTOPHANE 2, 3-DIOXYGENASES
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Paragraph 0135, (2016/10/31)
Disclosed herein are 5 or 8-substituted imidazo[l,5-a]pyridines and pharmaceutical compositions comprising at least one such 5 or 8-substituted imidazo[l,5-a]pyridines, processes for the preparation thereof, and the use thereof in therapy. Disclosed herein are certain 5 or 8- substituted imidazo[l,5-a]pyridines that can be useful for inhibiting indoleamine 2,3- dioxygenase and/or tryptophane 2,3-dioxygenase and for treating diseases or disorders mediated thereby.
Picolinic acid based acyclic bifunctional chelating agent and its methionine conjugate as potential SPECT imaging agents: Syntheses and preclinical evaluation
Kadiyala, K. Ganesh,Tyagi, Tulika,Kakkar, Dipti,Chadha, Nidhi,Chuttani, Krishna,Roy, Bal Gangadhar,Thirumal, Meganathan,Mishra, Anil K.,Datta, Anupama
, p. 33963 - 33973 (2015/04/27)
Bifunctional chelate, 6,6′-(2-aminoethylazanediyl)bis(methylene)dipicolinic acid (H2pentapa-en-NH2), has been synthesized and labeled with 99mTc with a specific activity of 135-140 MBq μmol-1 in >95% yield. The in vitro stability of the labeled chelate in both PBS and human serum shows only -1 uptake in other organs. The target specificity of the chelate towards tumor was introduced by conjugating two molecules of methionine. The conjugated probe H2pentapa-en-met2 was synthesized in >85% yield and labeled with 99mTc in 96.2% radiochemical yield with a specific activity of 110-125 MBq μmol-1. The conjugate probe exhibited high serum stability (>94% at 24 h). The in vivo blood kinetic studies of radiocomplexes of H2pentapa-en-NH2 and its methionine conjugated derivative exhibited fast clearance with t1/2(F) = 32 ± 0.14 min, t1/2(S) = 4 h 20 min ± 0.21 min and t1/2(F) = 27 ± 0.3 min, t1/2(S) = 4 h 01 min ± 0.11 min, respectively. In vivo scintigraphy and ex vivo biodistribution studies in EAT tumor bearing mice demonstrated a high retention of H2pentapa-en-met2 at the site of the tumor with tumor to muscle ratio of 6.52 at 1 h, indicating the high specificity of 99mTc-pentapa-en-met2 toward tumors.
Development of metal-chelating inhibitors for the Class II fructose 1,6-bisphosphate (FBP) aldolase
Labbe, Genevieve,Krismanich, Anthony P.,De Groot, Sarah,Rasmusson, Timothy,Shang, Muhong,Brown, Matthew D.R.,Dmitrienko, Gary I.,Guillemette, J. Guy
scheme or table, p. 49 - 58 (2012/09/21)
It has long been suggested that the essential and ubiquitous enzyme fructose 1,6-bisphosphate (FBP) aldolase could be a good drug target against bacteria and fungi, since lower organisms possess a metal-dependant (Class II) FBP aldolase, as opposed to higher organisms which possess a Schiff-base forming (Class I) FBP aldolase. We have tested the capacity of derivatives of the metal-chelating compound dipicolinic acid (DPA), as well a thiol-containing compound, to inhibit purified recombinant Class II FBP aldolases from Mycobacterium tuberculosis, Pseudomonas aeruginosa, Bacillus cereus, Bacillus anthracis, and from the Rice Blast causative agent Magnaporthe grisea. The aldolase from M. tuberculosis was the most sensitive to the metal-chelating inhibitors, with an IC50 of 5.2 μM with 2,3- dimercaptopropanesulfonate (DMPS) and 28 μM with DPA. DMPS and the synthesized inhibitor 6-(phosphonomethyl)picolinic acid inhibited the enzyme in a time-dependent, competitive fashion, with second order rate constants of 273 and 270 M- 1 s- 1 respectively for the binding of these compounds to the M. tuberculosis aldolase's active site in the presence of the substrate FBP (KM 27.9 μM). The most potent first generation inhibitors were modeled into the active site of the M. tuberculosis aldolase structure, with results indicating that the metal chelators tested cannot bind the catalytic zinc in a bidentate fashion while it remains in its catalytic location, and that most enzyme-ligand interactions involve the phosphate binding pocket residues.
