210366-15-7

Usage

Uses

Used in Pharmaceutical Industry:
2-Pyridinecarboxylic acid, 1,6-dihydro-6-oxo-1-(phenylMethoxy)is used as a pharmaceutical candidate for its potential therapeutic applications in the treatment of various diseases. Its unique structure and pharmacological properties make it a promising compound for drug development and discovery.
Used in Organic Synthesis:
2-Pyridinecarboxylic acid, 1,6-dihydro-6-oxo-1-(phenylMethoxy)is used as a key intermediate in organic synthesis, particularly for the synthesis of other pyridine-based compounds with potential applications in various fields, such as pharmaceuticals, agrochemicals, and materials science.
Used in Drug Development:
2-Pyridinecarboxylic acid, 1,6-dihydro-6-oxo-1-(phenylMethoxy)is used as a starting material or building block in drug development, where its unique structure and properties can be exploited to design and synthesize novel therapeutic agents with improved efficacy, selectivity, and safety profiles.

Upstream product

• 210366-13-5 methyl 1-(benzyloxy)-6-oxo-1,6-dihydropyridine-2-carboxylate 
• 100-44-7 benzyl chloride 
• 94781-89-2 1,2-dihydro-1-hydroxy-2-oxopyridine-6-carboxylic acid 
• 19621-92-2 6-Hydroxypicolinic acid 
• 210366-10-2 methyl-1-hydroxy-6-oxo-1,6-dihydropyridine-2-carboxylate 
• 1094194-45-2 6-carboxy-1,2-HOPO 
• 94781-88-1 6-bromopyridine-2-carboxylic acid-1-N-oxide 
• 21190-87-4 6-bromo-pyridine-2-carboxylic acid 
• 100-39-0 benzyl bromide 
• 19621-92-2 2-oxo-1,2-dihydropyridine-6-carboxylic acid 

Downstream Products

• 210366-17-9 1-(benzyloxy)-6-oxo-1,6-dihydropyridine-2-carboxylic acid chloride 
• 770738-07-3 1-(benzyloxy)-6-(2-thioxothiazolidine-3-carbonyl)pyridin-2(1H)-one 
• 910106-57-9 5LIO-1,2-HOPOBn 
• 460986-08-7 3,4,3-LI-(1,2-HOPOBn) 
• 460986-10-1 3,4,3-LI-(1,2-Me-3,2-HOPO)Bn 
• 1297532-40-1 TAM(o-phen-1,2-HOPO)2(Bn)4 
• 1297532-42-3 TAM(o-phen-1,2-HOPO)2 
• 210366-13-5 methyl 1-(benzyloxy)-6-oxo-1,6-dihydropyridine-2-carboxylate 

Relevant academic research and scientific papers

Alternative chelator for 89Zr radiopharmaceuticals: Radiolabeling and evaluation of 3,4,3-(LI-1,2-HOPO)

Zirconium-89 is an effective radionuclide for antibody-based positron emission tomography (PET) imaging because its physical half-life (78.41 h) matches the biological half-life of IgG antibodies. Desferrioxamine (DFO) is currently the preferred chelator for 89Zr4+; however, accumulation of 89Zr in the bones of mice suggests that 89Zr4+ is released from DFO in vivo. An improved chelator for 89Zr4+ could eliminate the release of osteophilic 89Zr4+ and lead to a safer PET tracer with reduced background radiation dose. Herein, we present an octadentate chelator 3,4,3-(LI-1,2-HOPO) (or HOPO) as a potentially superior alternative to DFO. The HOPO ligand formed a 1:1 Zr-HOPO complex that was evaluated experimentally and theoretically. The stability of 89Zr-HOPO matched or surpassed that of 89Zr-DFO in every experiment. In healthy mice, 89Zr-HOPO cleared the body rapidly with no signs of demetalation. Ultimately, HOPO has the potential to replace DFO as the chelator of choice for 89Zr-based PET imaging agents.

IRON(III) AND GALLIUM(III) METAL ORGANIC POLYHEDRA, METHODS OF MAKING SAME, AND USES THEREOF

Compounds may have at least two structural units, which may be referred to as ligands. Each structural unit includes at least one spacer group and two or more donor groups. Compounds may have two or more iron(III) cations, one or more of which may be a hi

Synthesis and iron chelating properties of hydroxypyridinone and hydroxypyranone hexadentate ligands

Chelation therapy has become an important therapeutic approach for some diseases. In attempt to identify clinically useful chelators, four hexadentate ligands were synthesized by conjugating the corresponding bidentate ligands (3-hydroxypyridin-4-one (3,4-HOPO), 3-hydroxypyridin-2-one (3,2-HOPO), 1-hydroxypyridin-2-one (1,2-HOPO), and 3-hydroxypyran-4-one) each with a free amino group to a tripodal acid. Their pKa values and affinities for iron(iii) were investigated. The pFe3+ values of the hexadentate pyridinones 1 (3,4-HOPO), 3 (3,2-HOPO) and 4 (1,2-HOPO), and the pyranone 2 was found to follow the sequence 1 > 4 ? 3 > 2, which is different to the pFe3+ value sequence of the corresponding bidentate forms (3,4-HOPO ? 3,2-HOPO > 1,2-HOPO > 3-hydroxypyranone). Hexadentate 3,4-HOPOs and 1,2-HOPOs have the greatest potential as iron scavenging agents.

COMPOSITIONS FOR THERAPEUTICS, TARGETED PET IMAGING AND METHODS OF THEIR USE

Described herein is a chelator for radiolabels (e.g., 89Zr) for targeted PET imaging that is an alternative to DFO. In certain embodiments, the chelator for 89Zr is the ligand, 3,4,3-(LI-1,2- HOPO) ("HOPO"), which exhibits equal or superior stability compared to DFO in chemical and biological assays across a period of several days in vivo. As shown in FIG. 1, the HOPO is an octadentate chelator that stabilizes chelation of radiolabels (e.g., 89Zr). A bifunctional ligand comprising p-SCN-Bn-HOPO is shown in FIG. 4 and FIG. 5. Such a bifunctional ligand can eliminate (e.g., 89Zr) loss from the chelate in vivo and reduce uptake in bone and non-target tissue. Therefore, the bifunctional HOPO ligand can facilitate safer and improved PET imaging with radiolabeled antibodies.

New insights into structure and luminescence of EuIII and SmIII complexes of the 3,4,3-LI(1,2-HOPO) ligand

We report the preparation and new insight into photophysical properties of luminescent hydroxypyridonate complexes [MIIIL]- (M = Eu or Sm) of the versatile 3,4,3-LI(1,2-HOPO) ligand (L). We report the crystal structure of this ligand

LUMINESCENT 1-HYDROXY-2-PYRIDINONE CHELATES OF LANTHANIDES

The present invention provides luminescent complexes between a lanthanide ion and an organic ligand which contains 1,2-hydroxypyridinone units. The complexes of the invention are stable in aqueous solutions and are useful as molecular probes, for example in medical diagnostics and bioanalytical assay systems. The invention also provides methods of using the complexes of the invention.

2-HYDROXY-1-OXO 1,2 DIHYDRO ISOQUINOLINE CHELATING AGENTS

The invention provides a new class of strongly chelating multidentate ligands based on a 2-hydroxy-1-oxo-1,2-dihydro-isoquinoline-3-carboxylic acid scaffold (hereafter 1,2-HOIQO) in combination with polyamine backbones. The extremely stable bidentate 1,2- HOIQO moiety can be synthesized by standard synthetic methodology on a large scale. An advantageous feature is the possibility to introduce a wide range of substituents on the benzene ring by standard transformations (like electrophilic aromatic substitutions). This allows, for example, for the tuning of chemical, photophysical, and solubility properties, as well as the attachment of functional moieties, relevant for sensing and imaging applications (e.g. DNA, proteins, antibodies, fluorophores, etc.). The combination of the 1,2-HOIQO chelators with polyamine backbones provides very strongly binding ligands for a variety of metals including first-row transition metals, lanthanides, actinides, etc. Metal complexes of this kind are expected to be useful in a number of applications (e.g. luminescence, MRI, actinide sequestering, metal chelation therapy, metal radioisotope labeling, etc.).

Hydroxypyridonate and hydroxypyrimidinone chelating agents

The present invention provides hydroxypyridinone and hydroxypyrimidone chelating agents. Also provides are Gd(III) complexes of these agents, which are useful as contrast enhancing agents for magnetic resonance imaging. The invention also provides methods of preparing the compounds of the invention, as well as methods of using the compounds in magnetic resonance imaging applications.

Synthesis and initial evaluation for in vivo chelation of Pu(IV) of a mixed octadentate spermine-based ligand containing 4-carbamoyl-3-hydroxy-1-methyl-2(1H)-pyridinone and 6-carbamoyl-1-hydroxy-2(1H)-pyridinone

An improved synthesis for a series of 1-hydroxy-2(1H)-pyridinone-based octadentate ligands is reported. The mixed chelate, octadentate ligand, 3,4,3-LI(1,2-Me-3,2-HOPO), was designed, synthesized, and tested for in vivo chelation of Pu in a mouse model. This ligand incorporates both 1,2-HOPO and Me-3,2-HOPO metal chelating units; the latter has higher affinity toward actinide ions than does 1,2-HOPO at physiological pH. Injected or administered orally to fasted or normally fed mice at the standard clinical dose 30 μmol/kg, both 3,4,3-LI(1,2-HOPO) and 3,4,3-LI(1,2-Me-3,2-HOPO) remove significantly more Pu than injected CaNa3DTPA. Injected doses of 0.1 μmol/kg of these HOPO ligands are as effective as 30 μmol/kg of injected CaNa3-DTPA. Ten daily injections of 30 μmol/kg of a HOPO ligand did not induce detectable acute toxicity in mice. The mixed HOPO ligand is somewhat more effective than 3,4,3-LI(1,2-HOPO) when given orally, and the enhanced reduction of liver Pu by the mixed ligand is statistically significant. Thus, both octadentate HOPO ligands meet the criterion of low toxicity at doses that are more effective than the standard dose of CaNa3DTPA. Their improved effectiveness at low dose along with great oral activity (despite low gastrointestinal absorption) implies that new treatment regimens can be developed using the HOPO ligands alone or as adjuncts to CaNa3DTPA therapy, which will greatly exceed the amount of Pu excretion that is achievable with CaNa3DTPA alone.

Synthesis of 3,4,3 LI 1,2 HOPO labelled with 14C

3,4,3 LI 1,2 HOPO 1 or LIHOPO (1,5,10,14-tetra (1-hydroxy-2-pyridone-6-oyl)-1,5,10,14-tetraazatetradecane.) is a decorporation agent used against actinides. It was synthesised labelled with carbon 14 with a view to metabolism studies. [6,9-14C]-LIHOPO 2 was obtained in two radioactive steps through a very convenient synthesis in 50% radioactive yield from commercially available [1,4-14C]-spermine, hydrochloride and 1-benzyloxy-6-oxo-1,6-dihydropyridine-2-carbonyl chloride 7. The synthesis of 7 is also described.