Synthetic Approaches to the Bifunctional Chelators for Radio­nuclides Based On Pyridine-Containing Azacrown Compounds

Abstract

Synthetic ways to introduce functional groups (CO2Me, CO2H, OCH2CO2H, OCH2C≡CH, CH2OH, CH2Cl, CH2N3) into the pyridine ring of pyridine-containing azacrown compounds are described. These groups were introduced at position-4 of the pyridine ring, while keeping the macrocyclic carboxylate groups available for metal chelation. The derivatives were obtained by macrocyclization reaction of 4-substituted, trimethyl pyridine-2,4,6-tricarboxylate or by modification of methyl ester group in pyridine fragment of macrocycles. Obtained derivatives can be applied for preparing radiotherapeutic agents by conjugation to different vector biomolecules for targeted drug delivery to cancer cells without damaging healthy tissue.

Expanding the Paradigm of Structure-Based Drug Design: Molecular Dynamics Simulations Support the Development of New Pyridine-Based Protein Kinase C-Targeted Agonists

“…We obtained the amide 6a (62% yield) by microwave irradiating the bis-methyl ester 3 with the commercially available 3-(trifluoromethyl)benzylamine in MeOH, adapting a method reported by Zubenko et al on related compounds. 41 For the 3-heptyl derivative, we synthesized 3-heptanamine ( SI2 , Scheme S1 ) via reductive amination of 3-heptanone ( SI1 , Scheme S1 ) as described by Kapoor et al 42 The synthesis of the bis-3-heptyl derivative 6b required a stronger basic environment as the same conditions applied for the bis-3-(trifluoromethyl)benzyl derivative 6a generated only the monosubstituted product in low yield. We first pretreated 3-heptanamine ( SI2 ) with NaH and then reacted it with the bis-methyl ester 3 in THF under microwave irradiation to obtain the bis-3-heptyl amide 6b in 36% yield.…”

Insights into Actinium Complexes with Tetraacetates─AcBATA versus AcDOTA: Thermodynamic, Structural, and Labeling Properties

“…Moreover, the H 4 BATA ligand can be bifunctionalized via the benzene group, decreasing the influence of the biomolecule due to the distancing from the cation-coordinating sites. Earlier, we have developed a strategy for the synthesis of the bifunctional derivative of similar pyridine azacrown ether . The ligand has been bound with nanoparticles via the group associated with pyridine, and the final conjugate was successfully labeled. , …”

“…Earlier, we have developed a strategy for the synthesis of the bifunctional derivative of similar pyridine azacrown ether. 55 The ligand has been bound with nanoparticles via the group associated with pyridine, and the final conjugate was successfully labeled. 56,57 Taken together, H 4 BATA is a superior candidate for further conjugation with antibodies and for the application in radioimmunotherapy by a 225 Ac radionuclide.…”

Synthesis of new acyclic chelators H4aPyta and H6aPyha and their complexes with Cu2+, Ga3+, Y3+, and Bi3+

“…This was demonstrated earlier with a pyridine-containing macrocyclic and acyclic analogs. [37][38][39][40] Since the ligands H 4 aPyta and H 6 aPyha have not been previously described, detailed investigations are required. For radiopharmaceutical applications, the conditions and timing of radioactive labeling and its effectiveness, stability in the presence of competing ions and serum proteins, as well as biological stability are important.…”