41337-81-9Relevant academic research and scientific papers
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.
Conversion of molecular information by luminescent nanointerface self-assembled from amphiphilic Tb(III) complexes
Liu, Jing,Morikawa, Masa-Aki,Kimizuka, Nobuo
, p. 17370 - 17374 (2011)
A novel amphiphilic Tb3+ complex (TbL+) having anionic bis(pyridine) arms and a hydrophobic alkyl chain is developed. It spontaneously self-assembles in water and gives stable vesicles that show sensitized luminescence of Tb3+ ions at neutral pH. This TbL + complex is designed to show coordinative unsaturation, i.e., water molecules occupy some of the first coordination spheres and are replaceable upon binding of phosphate ions. These features render TbL+ self-assembling receptor molecules which show increase in the luminescence intensity upon binding of nucleotides. Upon addition of adenosine triphosphate (ATP), significant amplification of luminescent intensity was observed. On the other hand, ADP showed moderately increased luminescence and almost no enhancement was observed for AMP. Very interestingly, the increase in luminescence intensity observed for ATP and ADP showed sigmoidal dependence on the concentration of added nucleotides. It indicates positive cooperative binding of these nucleotides to TbL+ complexes preorganized on the vesicle surface. Self-assembly of amphiphilic Tb3+ receptor complexes provides nanointerfaces which selectively convert and amplify molecular information of high energy phosphates linked by phosphoanhydride bonds into luminescence intensity changes.
NOVEL 5 OR 8-SUBSTITUTED IMIDAZO [1, 5-a] PYRIDINES AS INDOLEAMINE AND/OR TRYPTOPHANE 2, 3-DIOXYGENASES
-
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.
Amphiphilic Tb (III) complex and its preparation method for the preparation of fluorescent nano-fibers and method and application
-
Paragraph 0049-0051; 0053, (2017/02/02)
The invention relates to an amphiphilic Tb (III) complex, a preparation method thereof and a preparation method and application of fluorescent nano-fibers. By virtue of characteristics of a rigid framework, biocompatibility and self-assembling of cholesterol molecules, the amphiphilic Tb (III) complex containing a cholesterol structural unit and bi-picolinic acid is designed and prepared, the supermolecule fluorescent nano-fibers based on the amphiphilic Tb (III) complex are assembled, and action mechanisms of the fluorescent nano-fibers and aurintricarboxylic acid are researched; by virtue of synergetic complexing between aurintricarboxylic acid and ions of Tb (III) and an energy transfer process, aurintricarboxylic acid is efficiently sensed. Related reaction conditions are mild and easy to achieve, the preparation method of the fluorescent nano-fibers is simple, convenient and easy to operate, the prepared fluorescent nano-fibers are uniform in size, the sensitivity for detecting aurintricarboxylic acid is high, the selectivity is good, and the fluorescent nano-fibers are hopeful for being used for researching the pharmaceutical process of aurintricarboxylic acid.
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 an in vivo active, dual EP1 and EP3 selective antagonist based on a novel acyl sulfonamide bioisostere
Downey, Jason D.,Saleh, Sam A.,Bridges, Thomas M.,Morrison, Ryan D.,Scott Daniels,Lindsley, Craig W.,Breyer, Richard M.
, p. 37 - 41 (2013/02/23)
Recent preclinical studies demonstrate a role for the prostaglandin E 2 (PGE2) subtype 1 (EP1) receptor in mediating, at least in part, the pathophysiology of hypertension and diabetes mellitus. A series of amide and N-acylsulfonamid
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.
Synthesis and binding properties of guanidinium biscarboxylates
Spaeth, Andreas,Gonschor, Janina,Koenig, Burkhard
experimental part, p. 1289 - 1308 (2012/06/15)
The ammonium ion binding site of the enzyme glutaminase HisF inspired us to design guanidinium biscarboxylates as potential self-organized ionophores in molecular recognition. The syntheses of the title compounds based on aliphatic and aromatic building b
Selection and development of the manufacturing route for EP1 antagonist GSK269984B
Whiting, Matthew,Harwood, Kathy,Hossner, Frank,Turner, Peter G.,Wilkinson, Mark C.
experimental part, p. 820 - 831 (2011/03/19)
A potential manufacturing route for the EP1 antagonist GSK269984B was developed. Four synthetic approaches were examined, and a successful realisation of each is presented. The rationale supporting selection of the preferred route is discussed.
Discovery of sodium 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (GSK269984A) an EP1 receptor antagonist for the treatment of inflammatory pain
Hall, Adrian,Billinton, Andy,Brown, Susan H.,Chowdhury, Anita,Clayton, Nicholas M.,Giblin, Gerard M.P.,Gibson, Mairi,Goldsmith, Paul A.,Hurst, David N.,Naylor, Alan,Peet, Caroline F.,Scoccitti, Tiziana,Wilson, Alexander W.,Winchester, Wendy
scheme or table, p. 2599 - 2603 (2010/05/19)
We describe the medicinal chemistry programme that led to the identification of the EP1 receptor antagonist GSK269984A (8h). GSK269984A was designed to overcome development issues encountered with previous EP1 antagonists such as GW8
