169237-39-2

Upstream product

• 130879-43-5 3-methoxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxylic acid ethyl ester 
• 100-39-0 benzyl bromide 
• 500372-11-2 ethyl 3-hydroxy-2-oxo-1,2-dihydropyridine-4-carboxylate 
• 21472-88-8 5-hydroxy-6-oxo-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid ethyl ester 
• 84719-32-4 3-Hydroxy-2(1H)-pyridinone 
• 134469-06-0 thiazolidine-2-thione 
• 169237-38-1 3-benzyloxy-4-carboxy-1-methyl-2(1H)-pyridinone 
• 1025989-29-0 benzyl 3-(benzyloxy)-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxylate 
• 169237-37-0 4-carboxy-1-methyl-3-hydroxy-2(1H)-pyridinone 
• 19365-01-6 1-methyl-3-hydroxy-2(1H)-pyridinone 
• 96-53-7 2-mercaptothiazoline 

Downstream Products

• 169237-40-5 C₄₈H₅₁N₇O₉ 
• 186834-26-4 C₆₆H₇₂N₁₀O₁₂ 
• 1027954-03-5 C₆₇H₇₄N₁₀O₁₂ 
• 186834-20-8 C₃₁H₃₂N₄O₆ 
• 460986-09-8 3,4,3-LI-Bis(Me-3,2-HOPOBn) 
• 848490-02-8 3-benzyloxy-1-methyl-2-oxo-1,2-dihydro-pyridine-4-carboxylic acid (3-amino-propyl)-amide 
• 593247-69-9 TREN-1-Me-3,2-HOPO-TAM₂, benzyl protected 
• 460986-10-1 3,4,3-LI-(1,2-Me-3,2-HOPO)Bn 
• 518046-69-0 1-Bn-6-Me-3,2-HOPO-thiazolide 
• 186834-11-7 3-benzyloxy-1-methyl-4(1-propylcarbamoyl)-2(1H)-pyridinone 
• 186834-28-6 N,N-Bis(3-benzyloxy-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)carboxamido-ethyl-N-(2-aminoethyl)amine (Bn-TREN-Bis-Me-3,2-HOPO) 
• 872462-31-2 (4-(3-(bis-(2-((3-benzyloxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carbonyl)-amino)-ethyl)-amino)-2-((3-benzyloxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carbonyl)-amino)-propyl)-phenoxy)-acetic acid 
• 872462-35-6 5-[bis-(2-{[3-benzyloxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carbonyl]amino}ethyl)amino]-4-{[3-benzyloxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carbonyl]amino}pentanecarboxylic acid 
• 872465-08-2 6-(bis-(2-((3-benzyloxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carbonyl)-amino)-ethyl)-amino)-5-((3-benzyloxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carbonyl)-amino)-hexylcarbamic acid tert-butylester 

Relevant academic research and scientific papers

RADIO-PHARMACEUTICAL COMPLEXES

The invention provides a method for the formation of a tissue-targeting thorium complex, said method comprising; a) forming an octadentate chelator comprising four hydroxypyridinone (HOPO) moieties, substituted in the N-position with a methyl group, and a

RADIO-PHARMACEUTICAL COMPLEXES

The invention provides a method for the formation of a tissue-targeting thorium complex, said method comprising; a) forming an octadentate chelator comprising four hydroxypyridinone (HOPO) moieties, substituted in the N-position with a methyl group, and a

Alpha-emitting complexes

The present invention provides a tissue-targeting complex comprising a tissue targeting moiety, an octadentate hydroxypyridinone-containing ligand and the ion of an alpha-emitting thorium radionuclide. The invention additionally provides therapeutic methods employing such complexes, methods of their production and use, and kits and pharmaceutical compositions comprising such complexes.

An efficient chelator for complexation of thorium-227

We present the synthesis and characterization of a highly efficient thorium chelator, derived from the octadentate hydroxypyridinone class of compounds. The chelator forms extremely stable complexes with fast formation rates in the presence of Th-227 (ambient temperature, 20?min). In addition, mouse biodistribution data are provided which indicate rapid hepatobiliary excretion route of the chelator which, together with low bone uptake, supports the stability of the complex in vivo. The carboxylic acid group may be readily activated for conjugation through the ?-amino groups of lysine residues in biomolecules such as antibodies. This chelator is a critical component of a new class of Targeted Thorium Conjugates (TTCs) currently under development in the field of oncology.

RADIO-PHARMACEUTICAL COMPLEXES

The invention provides a method for the formation of a tissue-targeting thorium complex, said method comprising; a) forming an octadentate chelator comprising four hydroxypyridinone (HOPO) moieties, substituted in the N-position with a C l-C s

ALPHA-EMITTING COMPLEXES

The present invention provides a tissue-targeting complex comprising a tissue targeting moiety, an octadentate hydroxypyridinone-containing ligand and the ion of an alpha-emitting thorium radionuclide. The invention additionally provides therapeutic methods employing such complexes, methods of their production and use, and kits and pharmaceutical compositions comprising such complexes.

Specific sequestering agents for the actinides. 28. Synthesis and initial evaluation of multidentate 4-carbamoyl-3-hydroxy-1-methyl-2(1H)-pyridinone ligands for in vivo plutonium(IV) chelation

A new family of chelating agents based on 4-(substituted-carbamoyl)-3- hydroxy-2-pyridinones is reported. These have optional terminal substituents on the nitrogens, and the hydroxypyridonate (HOPO) rings are attached to molecular backbones through amide linkages. A very important feature of the methyl-substituted ligand derivatives (Me-3,2-HOPOs) is that, similarly to the catechoylamide complexes of the siderophore enterobactin and its analogs, these HOPO derivatives form strong hydrogen bonds between the amide proton and the adjacent oxygen of the phenolate in the metal complex; this enhances the stability of the complex. This rigidity helps to explain the great affinity of the Me-3,2-HOPO ligands for plutonium(IV), as observed here under physiological conditions. All 13 compounds studied significantly enhanced Pu excretion from mice compared with Pu-injected controls. Eight of the ligands studied promoted significantly more Pu excretion than an equal molar amount of CaNa3-DTPA (the compound in present clinical use). Five injected and two orally administered Me-3,2-HOPO ligands promoted as much or slightly more Pu excretion than an equal molar amount of the octadentate 3,4,3-LI(1,2-HOPO), the previously most effective in vivo ligand. Surprisingly, although plutonium has an eight-coordination requirement, tetra- and hexadentate Me- 3,2-HOPO ligands were essentially as effective as the one octadentate ligand studied. These observations suggest that even the tetradentate Me-3,2-HOPO ligands compete with mammalian transferrin for Pu(IV). For the three most promising compounds, there is no acute toxicity seen up to the highest dose administered, which was 1000 μmol/kg. One compound, the hexadentate TREN- (Me-3,2-HOPO), is particularly effective, either injected or orally, and an exceptionally good in vivo chelator of several actinides in addition to Pu(IV). Three of these compounds studied have low toxicity and are relatively simple and inexpensive to prepare. They are promising therapeutic agents.