Synthesis and fungicidal activity of tubulin polymerisation promoters. Part 2: Pyridazines

Lamberth, Clemens; Trah, Stephan; Wendeborn, Sebastian; Dumeunier, Raphaël; Courbot, Mikaël; Godwin, Jeremy; Schneiter, Philippe

doi:10.1016/j.bmc.2012.03.035

Cited by 41 publications

(27 citation statements)

References 24 publications

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“…Among these classes of compounds are certain triazolopyrimidines, typified by 2 , 10 as well as some structurally related phenylpyrimidines, 16 pyridopyridazines, 18 and pyridazines. 15 The first examples of these synthetic small molecule MT-stabilizing agents were members of the triazolopyrimidines discovered as antifungal agents. 25 Since then, improved analogues, as well as related scaffolds, have been reported that appear to share similar MT-stabilizing properties, antimitotic activity, and structure–activity relationships.…”

Section: Discussionmentioning

confidence: 99%

“…25 Since then, improved analogues, as well as related scaffolds, have been reported that appear to share similar MT-stabilizing properties, antimitotic activity, and structure–activity relationships. 10,15,16,18,26,27 Interestingly, radioligand binding studies suggested that the mode of action of these heterocyclic MT-stabilizing agents may be rather unique. 28,29 Whereas 2 was found not to compete for the taxane/epothilone binding site on β-tubulin, this compound did affect vinblastine binding to β-tubulin.…”

Section: Discussionmentioning

confidence: 99%

“…7 was prepared as described in Lamberth et al 15 Reverse-phase HPLC purification of the crude product afforded the title compound. 1 H NMR (500 MHz; CDCl 3 ) δ 6.83 (d, J = 3.8 Hz, 1H), 6.73–6.70 (m, 3H), 2.71 (s, 3H) ppm.…”

Section: Methodsmentioning

confidence: 99%

“…Phthalimide derivative 5 (13) and pyridazines 6 (14) and 7 (15) (Figure 1) were synthesized as previously described. The synthesis of 2 (Figure 1) and related triazolopyrimidines ( 8 – 19 , Scheme 1) and phenylpyrimidines ( 20 – 25 , Scheme 1), which included a series of new analogues ( 10 , 13 – 17 , 19 , 24 , and 25 ), was accomplished following the general synthetic approach depicted in Scheme 1.…”

Section: Chemistrymentioning

confidence: 99%

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Brain-Penetrant, Orally Bioavailable Microtubule-Stabilizing Small Molecules Are Potential Candidate Therapeutics for Alzheimer’s Disease and Related Tauopathies

et al. 2014

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Microtubule (MT) stabilizing drugs hold promise as potential treatments for Alzheimer’s disease (AD) and related tauopathies. However, thus far epothilone D has been the only brain-penetrant MT-stabilizer to be evaluated in tau transgenic mice and in AD patients. Furthermore, this natural product exhibits potential deficiencies as a drug candidate, including an intravenous route of administration and the inhibition of the P-glycoprotein (Pgp) transporter. Thus, the identification of alternative CNS-active MT-stabilizing agents that lack these potential limitations is of interest. Toward this objective, we have evaluated representative compounds from known classes of non-naturally occurring MT-stabilizing small molecules. This led to the identification of selected triazolopyrimidines and phenylpyrimidines that are orally bioavailable and brain-penetrant without disruption of Pgp function. Pharmacodynamic studies confirmed that representative compounds from these series enhance MT-stabilization in the brains of wild-type mice. Thus, these classes of MT-stabilizers hold promise for the development of orally active, CNS-directed MT-stabilizing therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

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Brain-Penetrant, Orally Bioavailable Microtubule-Stabilizing Small Molecules Are Potential Candidate Therapeutics for Alzheimer’s Disease and Related Tauopathies

et al. 2014

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“…[1][2][3] Analogously, agricultural science takes advantage of their high biological activity, and pyridazines whose substitution patterns have been modified display powerful fungicide properties. [4][5][6] Furthermore, simple pyridazines rate high as halogen-free flame retardants. [7] Pyridazines have also been used as ligands in coordination chemistry.…”

Section: Introductionmentioning

confidence: 99%

Pyridazine‐Based Ligands and Their Coordinating Ability towards First‐Row Transition Metals

et al. 2010

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Tridentate pyridazine ligands with two different substituents at the 3-and 6-positions (pyridyl hydrazone at the 3-position and tolyl 3 tol or tert-butyl 3 tBu at the 6-position) were prepared in high yields from 3,6-disubstituted pyridazine hydrazines and pyridine aldehyde by Schiff base condensation. This provides a facile entry into a novel class of heterocyclic molecules exhibiting interesting coordinating abilities. They react with first-row transition metal nitrates to yield complexes of the type [ tol form complexes of the ML 2 type, whereas with ligand 3 tBu exclusively complexes of the ML type are formed,

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Probing the variations of synthesis, antimicrobial activity, and optical properties of new lanthanide and transition metal complexes of salicylaldehyde‐dipropylenetriamine ligand

Ebqa'ai,

Reed,

Seni

et al. 2024

Applied Organom Chemis

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Due to their notable antimicrobial activity and optical properties, Schiff base ligands, along with their lanthanide and transition metal complexes, have seen extensive use in various applications. However, despite their potential, a comprehensive investigation into lanthanide and transition metal complexes using the same Schiff base ligand has not been reported to date. In this study, coordination compounds of lanthanide and transition metal ions were synthesized from the Schiff base ligand salicylaldehyde‐dipropylenetriamine. These complexes were characterized by elemental analysis, 1H and 13C NMR, mass spectroscopy, Fourier‐transform infrared spectroscopy ultraviolet–visible spectroscopy (UV–Vis), fluorescence spectroscopy, molar conductivity measurements, and thermogravimetric studies. Furthermore, the molecular structure of the Co (II) complex was determined by means of X‐ray crystallography. Thermogravimetric studies illustrated endothermic and non‐spontaneous degradation pathways of the complexes. UV–Vis spectra showed a new absorption band attributed to the ligand‐to‐metal charge transfer peak supporting the complexation between the ligand and metals. The lanthanide complexes exhibited distinctive luminescence emissions in the Sm (III), Tb (III), and Eu (III) complexes. This observation suggests that the ligand possesses the capability to absorb and efficiently transfer energy to the metal center of these lanthanide ions, thereby resulting in their characteristic luminescent properties. Additionally, antimicrobial investigations revealed that transition metal complexes generally exhibited antimicrobial activity against both gram‐positive and gram‐negative bacterial strains compared to lanthanide metal complexes, in most cases. However, it is noteworthy that the Dy (III) complex displayed the lowest minimum inhibitory concentration and minimum biocidal concentration values of 16 μg/ml against Staphylococcus epidermidis, indicating its potential as a candidate for the treatment of this pathogenic bacterium. The main purpose of this article is to investigate the variations in the synthesis and characterization of lanthanide and transition metal complexes utilizing the same Schiff base ligand suitable for applications in the pharmaceutical industry and optical material sciences.

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Synthesis and fungicidal activity of tubulin polymerisation promoters. Part 2: Pyridazines

Cited by 41 publications

References 24 publications

Brain-Penetrant, Orally Bioavailable Microtubule-Stabilizing Small Molecules Are Potential Candidate Therapeutics for Alzheimer’s Disease and Related Tauopathies

Brain-Penetrant, Orally Bioavailable Microtubule-Stabilizing Small Molecules Are Potential Candidate Therapeutics for Alzheimer’s Disease and Related Tauopathies

Pyridazine‐Based Ligands and Their Coordinating Ability towards First‐Row Transition Metals

Probing the variations of synthesis, antimicrobial activity, and optical properties of new lanthanide and transition metal complexes of salicylaldehyde‐dipropylenetriamine ligand

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