Synthesis of n-chloroquinolines and n-ethynylquinolines (n=2, 4, 8): homo and heterocoupling reactions

Rodriguez, Jose Gonzalo Gonzalez; Rı́os, Cristóbal de los; Lafuente, Alfredo Liñán

doi:10.1016/j.tet.2005.07.043

Cited by 25 publications

(17 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To a 10 mL round bottom flask, charged freshly prepared solutions of 1 M sodium ascorbate (0.26 mL, 0.051 mmol) and CuSO 4 ·5H 2 O (0.15 mL, 0.031 mmol), TBTA (5.41 mg, 0.01 mmol) in THF/H 2 O (3:1, 4 mL) was added 3-ethynylquinoline (78.1 mg, 0.51 mmol) 42 and azide 15 (175.0 mg, 0.51 mmol). The reaction mixture was stirred for 16 h at room temperature before it was diluted with H 2 O (2 mL) and extracted with EtOAc (3 × 3 mL).…”

Section: Experimental Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Using click chemistry toward novel 1,2,3-triazole-linked dopamine D3 receptor ligands

Keck

Banala

Slack

et al. 2015

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

The dopamine D3 receptor (D3R) is a target of pharmacotherapeutic interest in a variety of neurological disorders including schizophrenia, Parkinson's disease, restless leg syndrome, and drug addiction. A common molecular template used in the development of D3R-selective antagonists and partial agonists incorporates a butylamide linker between two pharmacophores, a phenylpiperazine moiety and an extended aryl ring system. The series of compounds described herein incorporates a change to that chemical template, replacing the amide functional group in the linker chain with a 1,2,3-triazole group. Although the amide linker in the 4-phenylpiperazine class of D3R ligands has been previously deemed critical for high D3R affinity and selectivity, the 1,2,3-triazole moiety serves as a suitable bioisosteric replacement and maintains desired D3R-binding functionality of the compounds. Additionally, using mouse liver microsomes to evaluate CYP450-mediated phase I metabolism, we determined that novel 1,2,3-triazole-containing compounds modestly improves metabolic stability compared to amide-containing analogues. The 1,2,3-triazole moiety allows for the modular attachment of chemical subunit libraries using copper-catalyzed azide-alkyne cycloaddition click chemistry, increasing the range of chemical entities that can be designed, synthesized, and developed toward D3R-selective therapeutic agents.

show abstract

Section: Experimental Methodsmentioning

confidence: 99%

“…41 Therefore, while the coupling of azide 15 with 3-ethynylquinoline in the absence of TBTA did not provide the triazole 17b , the addition of the polytriazole to the same reaction conditions cleanly yielded the desired 17b . 42 …”

Section: Chemistrymentioning

confidence: 99%

Using click chemistry toward novel 1,2,3-triazole-linked dopamine D3 receptor ligands

Keck

Banala

Slack

et al. 2015

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…We prepared the 3-ethynyl derivative starting from 3-bromoquinoline 9 which was subjected to a literature-known Sonogashira coupling to give 10 in excellent yield. 42 Deprotection was then accomplished by a method developed by us earlier 43 employing solid potassium hydroxide and potassium phosphate in toluene to give 3-ethynylquinoline 11 in almost quantitative yield. Next we tried several methylation conditions.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, characterization and palladium complex formation of pyridinium- and quinolinium-3-acetylides: mesomeric betaines or betaine-stabilized carbenes?

et al. 2015

View full text Add to dashboard Cite

“…All reagents were purchased as reagent grade from commercial suppliers and used without further purification unless otherwise indicated. 2-Ethynylquinoline, 16 2-azidoethyl-4-methylbenzenesulfonate, 17 1-azidopropanol, 18 and 4-(2-azidoethyl)morpholine 15i were synthesized according to previously reported literature protocols. Safety Precautions in Handling of Azides: Some azides are hazardous, and to avoid injury, follow safe laboratory practices, wear appropriate protective equipment and use appropriate shielding equipment.…”

Section: Methodsmentioning

confidence: 99%

Multifunctional quinoline-triazole derivatives as potential modulators of amyloid-β peptide aggregation

Jones

Dyrager

Hoarau

et al. 2016

Journal of Inorganic Biochemistry

View full text Add to dashboard Cite

Metal ion dyshomeostasis is hypothesized to play a role in the toxicity and aggregation of the amyloid beta (Aβ) peptide, contributing to Alzheimer's disease (AD) pathology. We report on the synthesis and metal complexation ability of three bidentate quinoline-triazole derivatives 3-(4-(quinolin-2-yl)-1H-1,2,3-triazol-1-yl)propan-1-ol (QOH), 4-(2-(4-(quinolin-2-yl)-1H-1,2,3-triazol-1-yl)ethyl)morpholine (QMorph), and 4-(2-(4-(quinolin-2-yl)-1H-1,2,3-triazol-1-yl)ethyl)thiomorpholine (QTMorph). We further study the utility of these ligands to modulate Aβ peptide aggregation processes in the presence and absence of Cu 2+ ions. Ligand-peptide interactions were first investigated using both 2-D 1 H-15 N SOFAST-HMQC NMR spectroscopy and molecular modeling techniques, indicating interactions with E3 and several residues in the hydrophobic region of Aβ. Native gel electrophoresis with western blotting along with transmission electron microscopy provided information on the ability of each ligand to modulate Aβ aggregation. While the ligands alone did not modify Aβ peptide aggregation at the 24 hour timepoint, signifying relatively weak ligand-peptide interactions, the ligands did modify the aggregation profile of the peptide in the presence of stoichiometric and suprastoichiometric Cu. Interestingly, the thioether derivative QTMorph exhibited the most pronounced effect on peptide aggregation in the presence of Cu. Overall, the quinoline-triazole ligand series were shown to interact with the hydrophobic region of the Aβ peptide, and modulate Cu-Aβ aggregation process.

show abstract

Synthesis of n-chloroquinolines and n-ethynylquinolines (n=2, 4, 8): homo and heterocoupling reactions

Cited by 25 publications

References 31 publications

Using click chemistry toward novel 1,2,3-triazole-linked dopamine D3 receptor ligands

Using click chemistry toward novel 1,2,3-triazole-linked dopamine D3 receptor ligands

Synthesis, characterization and palladium complex formation of pyridinium- and quinolinium-3-acetylides: mesomeric betaines or betaine-stabilized carbenes?

Multifunctional quinoline-triazole derivatives as potential modulators of amyloid-β peptide aggregation

Contact Info

Product

Resources

About