Pyridazine Moieties Research Articles

The anticancer and anti-inflammatory activity screening of pyridazinone-based analogs against human epidermoid skin cancer with detailed mechanistic analyses

3(2H)-Pyridazinone derivatives based on 4-biphenyl, naphtha-2-yl, pyridine, or piperidine moiety were synthesized and characterized using I-R and 1HNMR spectra. The activity and cytotoxicity of some synthesized compounds on the skin epidermoid cancer cell proliferation and progression were investigated. The pyridazine isomer with pyridine revealed a significant decrease in the level of nitric oxide p < 0.01 than the activity of caffeine phenecyl ester. The activity of the three active isomers recorded significant activity for their total antioxidant content that triggers their ability for the scavenging the oxygen free radicals significantly p < 0.01. Moreover, revealing the pharmaceutical activity of the isomers as anti-inflammatory agents, IL-6, IL10, and IL12 have been decreased by variable significant values. Additionally, the active isomers revealed variable actions on the skin cancer cell to induce apoptosis using annexin V-FITC/PI. Pyridine was the highest isomer to induce late apoptosis and necrosis for the skin cancer cells against the use of cisplatin. Importantly, Molecular modeling experiments including docking and dynamic simulations were done for the most active 3 analogs to explore the ligand binding and stability leading to exploring the structure-activity relationship with biological target PARP1 which showed a good binding propensity to pyridazine binding site which supports the in vitro data. In conclusion, the pyridazine moieties with piperdine, naphthayl, and pyridine have pharmacological activities against skin cancer epidermoid by triggering action in inhibition of the proliferation and progression with an up-regulated apoptotic mechanism that evades the emergence of cisplatin resistance among different cancer cells. Communicated by Ramaswamy H. Sarma

Solvent-dependent alignments and halogen-related interactions in inclusion crystals of adamantane-based macrocycle with pyridazine moieties

Six inclusion crystals were formed from crystallization of an adamantane-based macrocycle bearing pyridazine parts in various solvents. In inclusion crystals with cyclic ethers, halogen⋯halogen interactions between the macrocycles were observed.

Synthesis and Preliminary Biological Properties Assessment of Novel 2-S-, 4-, 5-Substituted and Bicyclic Derivatives of 6-Methylpyrimidine-4-ol

: A series of novel 2-S-, 4-, 5-substituted and bicyclic 6-methylpyrimidine-4-ol derivatives including pyrazole, 1,2,4-triazole and pyridazine moieties in the molecule were synthesized by accessible and efficient methods. Thiopyrazolyl derivatives were obtained from 2-mercapto-6-methylpyrimidin-4-ol. 4-Triazolyl and 4-aminotriazolylpyrimidines were synthesized from the quaternary ammonium salt of pyrimidine and 4-chloro-substituted 2-thiomethyl-6-methylpyrimidine, respectively. The reaction of potassium salt of 1-methyl-6-oxo-1,6-dihydropyridazin-3-ole with ethyl 2-chloro-3-oxobutanoate and subsequent treatment with thiourea led to 6-((4-hydroxy-2-mercapto-6-methylpyrimidin-5-yl)oxy)-2- methylpyridazin-3 (2H)-one. The reaction product of the latter with 3-chloropentan-2,4-dione was subjected to heterocyclization, which afforded the target bicyclic derivative of pyrimidine. The synthesized compounds showed a pronounced stimulating action on plants growth. Their growth stimulant activities were in the range of 60-93% compared to heteroauxin.

Light-Enhanced Fluorescence of Multi-Level Cavitands Possessing Pyridazine Upper rim.

Completely different fluorescence behaviour of cavitands based on a same calix[4]resorcinarene compound was observed. While the fluorescence intensity of the parent compound, tetramethyl-cavitand (1) slowly faded as a result of UV-light exposure, the emission of the three-level cavitand with pyridazine moieties at the upper rim (5a) was enhanced by the excitation in the UV-region. The structure of fluorescence emission (characterized by excitation-emission matrices) and the absorption of 5a remained unaltered. The analysis of fluorescence decay curves reveals the presence of two separated components assigned to two individual emitting species. The measured significant increase of the average lifetime and quantum yield is the consequence of the UV-light induced transition between the different states of 5a. These observations can be explained by the structural difference between 5a and 1. As a counterpart of the naked cavitand (1) with methyl substituents at the upper rim only, 5a has three additional moieties benzene, triazole and pyridazine levels. Computational studies proved the existence of two conformational isomers of 5a. Upon ultraviolet light excitation a "dark" to "light" conformational transition occurs between the two isomers. This hypothesis was confirmed by anisotropy decay measurements.

Photochromism of dihydroindolizines. Part 16: Tuning of the photophysical behavior of photochromic dihydroindolizines in solution and in polymeric thin film

In this work, photochromic materials based on the dihydroindolizine (DHI) system were synthesized in multistep reactions using chemical and photochemical methods. Some of the synthesized photochromic dihydroindolizine derivatives were substituted on the fluorene (region A) and pyridazine (region C) moieties in order to provide the appropriate functionality for optimal tuning of the photochromic properties of the system. Irradiation of the photochromic DHIs with polychromatic light led to ring opened colored betaines, which underwent thermal 1,5-electrocyclization. The red to green colored betaines produced after UV irradiation returned back through 1,5-electrocyclization to the corresponding DHIs with different rate constants depending on the substituents in both fluorene and pyridazine regions. The kinetic measurements of the thermal 1,5-electrocyclization under different temperatures that ranged from −10 to 25 °C showed that the half-lives of the colored betaines fall in the second to hours domain. Interestingly, these materials showed a very good photochromic behavior not only in solution but also in the PMMA matrix. Irradiation of a slide prepared by the deep-coating method led to the formation of the colored betaine and the kinetics of the thermally reversible 1,5-electrocyclization and the AFM image of the film has been recorded. Indeed, the chemical and thermal stability of the investigated betaines in polymer (PMMA) will render such species useful for a plethora of new of applications.

ChemInform Abstract: Rod‐Like Conjugated Molecules with Ethynylene Linkage and Pyridazine Moieties: Synthesis and Light Emitting Properties.

AbstractA series of title compounds are prepared using Sonogashira cross‐coupling and condensation reactions.

ChemInform Abstract: Synthesis of Diarylsulfides and Diarylsulfones Containing Pyrazoline, Isoxazoline, Pyrimidine and Condensed Pyridazine Moieties.

ChemInform Abstract: Synthesis of Diarylsulfides and Diarylsulfones Containing Pyrazoline, Isoxazoline, Pyrimidine and Condensed Pyridazine Moieties.

Photochromism of dihydroindolizines: part XIV. Synthesis and photophysical behavior of photochromic dihydroindolizine-tripodal linkers toward anchoring sensitizers to semiconductor nanoparticles

Photochromic dihydroindolizines (DHIs) 4a,5-dihydropyrrolo[1,2-b]pyridazine based tripodal-linker systems with adamantane core and ethyl benzoate tripods as anchoring groups have been successfully synthesized. In addition, new spirocyclopropene precursors have been prepared through both chemical and photochemical processes. The photochromic properties of the newly synthesized DHIs derivatives have been optimized and fine-tuned by the incorporation of various substituents on the fluorene (region A) and pyridazine (region C) moieties. Several alternative routes for the synthesis of the DHIs under investigation have been established. The Sonogashira crosscoupling reaction was utilized for fragment coupling between DHIs and the phenylacetylene tether of the adamantane core. Several reaction conditions of this key reaction were surveyed to obtain optimal yields of a new series of coupling products targeted for anchoring to semiconductor nanoparticles. The chemical structures of the newly synthesized materials were elucidated by both analytical and spectroscopic tools. Irradiation of the photochromic DHIs with polychromatic light resulted in ring opened colored betaines which underwent cycloreversion reactions via thermal 1,5-electrocyclization processes. The kinetic of the thermal 1,5-electrocyclization was studied by using a UV/VIS/NIR spectrophotometer. The kinetic measurements showed the half-lives of the colored betaines to be in the second domain. A pronounced increase in the half-lives of betaines bearing dimethyl-substituted pyridazine was noted compared with non-substituted pyridazine betaines. A strong effect of solvent polarity on the λmax and half-lives of the betaines was observed. The further adjustment of the absorption maxima and the kinetic properties via the manipulation of substituents on the fluorene (region A) and pyridazine moieties (region C) should yield more refined systems for application as supports onto metal-oxide surfaces which remains an active area of our ongoing research. Copyright © 2010 John Wiley & Sons, Ltd.

Palladium‐Catalyzed Cross‐Coupling Reactions on Pyridazine Moieties

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis and Copper(I) Complexation of 3,6-Di(2-pyridyl)pyridazine and 2,2′-Bipyridine Ligands Functionalized with a Dangling Iridium(III) Complex

The combination of multiple metal complexes into single heterometallic architectures is of interest to study energy and electron transfer processes. In this contribution, the synthesis and characterization of iridium(iii) complexes with pendant dipyridyl–pyridazine and bipyridine moieties are reported. The successful coupling of an amino-functional mixed ligand IrIII complex was performed by a carbamate linkage using carbonyl-diimidazole-activated ligands. Characterization by 1H NMR spectroscopy, MALDI-TOFMS, and elemental analysis proved the purity of the synthesized complexes. Further, the complexation of these ligands with copper(i) ions and the effect of complexation on the phosphorescence of the IrIII complex are discussed, whereby model complexation studies were performed to further understand the observed quenching behaviour.

Palladium-Catalysed Cross-Coupling Reactions on Pyridazine Moieties

This Account focuses on the palladium-catalysed cross-coupling reactions of pyridazines. The pyridazine moiety is of significant importance in the pharmaceutical as well as the agrochemical field. Synthetic transformations on this moiety, to yield several diverse analogues for a wide array of applications, have received a considerable boost with the advent of palladium-catalysed cross-coupling reactions. These reactions facilitate the direct introduction of suitable groups on the pyridazine nucleus via carbon-carbon or carbon-heteroatom bond formations. This Account presents a brief account of the inherent advantages of palladium chemistry on this moiety followed by seminal work and subsequent developments on this topic.

Synthesis and characterization of poly(arylene ether)s containing 6‐(4‐hydroxyphenyl)pyridazin‐3(2H)‐one or 6‐(4‐hydroxyphenyl)pyridazine moieties

AbstractA series of novel soluble pyridazinone‐ or pyridazine‐containing poly(arylene ether)s were prepared by a polycondensation reaction. The pyridazinone monomer, 6‐(4‐hydroxyphenyl)pyridazin‐3(2H)‐one (1), was synthesized from the corresponding acetophenone and glyoxylic acid in a simple one‐pot reaction. The pyridazinone monomer was successfully copolymerized with bisphenol A (BPA) or 1,2‐dihydro‐4‐(4‐hydroxyphenyl)phthalazin‐1(2H)‐one (DHPZ) and bis(4‐fluorophenyl)sulfone to form high‐molecular‐weight polymers. The copolymers had inherent viscosities of 0.5–0.9 dL/g. The glass‐transition temperatures (Tg's) of the copolymers synthesized with BPA increased with increasing content of the pyridazinone monomer. The Tg's of the copolymers synthesized from DHPZ with different pyridazinone contents were similar to those of the two homopolymers. The homopolymers showed Tg's from 202 to 291 °C by differential scanning calorimetry. The 5% weight loss temperatures in nitrogen measured by thermogravimetric analysis were in the range of 411–500 °C. 4‐(6‐Chloropyridazin‐3‐yl)phenol (2) was synthesized from 1 via a simple one‐pot reaction. 2 was copolymerized with 4,4′‐isopropylidenediphenol and bis(4‐fluorophenyl)sulfone to form high‐Tg polymers. The copolymers with less than 80 mol % pyridazinone or chloropyridazine monomers were soluble in chlorinated solvents such as chloroform. The copolymers with higher pyridazinone contents and homopolymers were not soluble in chlorinated solvents but were still soluble in dipolar aprotic solvents such as N‐methylpyrrolidinone. The soluble polymers could be cast into flexible films from solution. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3328–3335, 2006

Synthesis of pyridazinyl ligands for multimetallic complexes

A family of ligands based upon the linking of two or three bis-(2-pyridyl)pyridazine (dppz) moieties via the 4- or 4,5-positions of the pyridazine rings has been synthesised using an inverse electron demand Diels–Alder pathway. Thus, reaction of 3,6-di(2-pyridyl)-1,2,4,5-tetrazine (dptz) with a series of dienes (1,4-divinylbenzene, 1,5-cyclooctadiene, norbornadiene, 1,5-hexadiene or 1,4-cyclohexadiene), diketones (1,4-diacetylbenzene), or trienes (trans,trans,cis-1,5,9-cyclododecatriene or trans,trans,trans-1,5,9-cyclododecatriene) has been studied and seven ligands isolated, namely 4,4′-(1,4-phenylene)bis(3,6-dipyridin-2-ylpyridazine) (L1), 5,6,11,12-tetrahydro-1,4,7,10-tetrapyridin-2-ylcycloocta[1,2-d:5,6-d′]dipyridazine (L2), 5,10-methano-1,4,6,9-tetrapyridin-2-ylpyridazino[4,5-g]phthalazine (L3), 4,4′-ethane-1,2-diylbis(3,6-dipyridin-2-ylpyridazine) (L4), 1,4,6,9-tetrapyridin-2-ylpyridazino[4,5-g]phthalazine (L5), cyclododeca[1,2-d:5,6-d′]dipyridazine-(11Z)-5,6,11,12,15,16-hexahydro-1,4,7,10-tetrapyridin-2-yl (L6) and 5,6,11,12,17,18-hexahydro-1,4,7,10,13,16-hexapyridin-2-ylcyclododeca[1,2-d:5,6-d′:9,10-d″]tripyridazine (L7). Compounds L1, L2 and L4 have been characterised by single crystal X-ray diffraction revealing the formation of molecular stacking in the solid-state via π–π interactions between dppz moieties. The potential of these ligands to form multimetallic complexes has been demonstrated by the successful synthesis and structural characterisation of {[Cu4(L1)(NO3)6(MeO)2(MeOH)2]}, {[Cu4(L1)(NO3)6(MeO)2(EtOH)2]}, {[Cd(NO3)(EtOH)3][Cd(NO3)3(L2)]} and {[Cd(NO3)2]2(L5)3}.

Dimetallic complexes of a structurally versatile pyridazine-containing Schiff-base macrocyclic ligand with pendant pyridine arms

The new [2 + 2] Schiff-base macrocyclic ligand L2, containing pyridazine head units and pyridine pendant arms, was synthesised as [Ba(II)2L2(ClO4)4(OH2)] 1 from the barium(II) ion templated condensation reaction of 3,6-diformylpyridazine and N1-(2-aminoethyl)-N1-(methylene-2-pyridyl)-ethane-1,2-diamine. Subsequent transmetallation reactions of 1 with copper(II), iron(II) and manganese(II) perchlorates led to the formation of [Cu(II)2L2](ClO4)4.2MeCN 2, [Fe(II)2L2(MeCN)2](ClO4)4 3 and two manganese complexes, 4 and 5, with the same formula, [Mn(II)2L2(MeCN)(OH2)](ClO4)4, but slightly different crystal structures, respectively. Single-crystal X-ray structural analyses reveal the variety of structures which can be supported by L2 in order to meet the coordination environment preferences of the incorporated metal ions. The barium(II) ions in 1 have an irregular ten-coordinate geometry whereas the copper(II) ions in 2 have a square pyramidal geometry and the iron(II) ions in 3 have an octahedral geometry, while in 4 and 5 every manganese(II) ion is seven-coordinate and the environment can be best described as distorted pentagonal bipyramidal. In 1, 4 and 5 the pyridazine moieties bridge the metal centres [Ba(1)...Ba(2) 4.9557(3)A 1; Mn(1)...Mn(2) 4.520(1)A 4; Mn(1)[dot dot dot]Mn(2) 4.3707(8)A 5] but this is not observed in the copper(II) and iron(II) complexes, 2 and 3, in which the metal ions are well separated [Cu(1)...Cu(2) 5.9378(6)A 2; Fe(1)...Fe(2) 5.7407(12)A 3]. In the cyclic voltammogram of [Cu2(II)L2](ClO4)4.2MeCN 2 in MeCN vs. Ag/AgCl two separate reversible one-electron transfer steps are observed [E(1/2)=0.04 V, DeltaE= 0.12 V and E(1/2)= 0.20 V, DeltaE=0.12 V; K(c)=510; in this system E(1/2)(Fc+/Fc)=0.42 V and DeltaE(Fc+/Fc)=0.08 V]. The other complexes cannot be reversibly reduced/oxidised.

Cover Picture: Coordination Algorithms Control Molecular Architecture: [CuI4(L2)4]4+ Grid Complex Versus [MII2(L2)2X4]y+ Side‐By‐Side Complexes (M=Mn, Co, Ni, Zn; X=Solvent or Anion) and [FeII(L2)3][Cl3FeIIIOFeIIICl3] (Chem. Eur. J. 16/2003)

AbstractThe cover picture shows how differing coordination algorithms control the molecular architecture of complexes of the pyridazine‐containing, two‐armed, acyclic Schiff base ligand L2 (left, prepared from one equivalent of 3,6‐diformylpyridazine and two equivalents of d‐anisidine). Two very different complexes of L2 self‐assemble from tetrahedral copper(I) versus octahedral zinc(II), nickel(II), and cobalt(II) controlled 1 : 1 reactions with L2. In both cases the metal ions are bridged by the pyridazine moieties in L2, but in the case of the tetrahedral copper(II) the result is a tetrametallic [2×2] grid complex ([CuI4(L2)4]4+: top right), whilst in the case of the octahedral metal(II) ions dimetallic side‐by‐side complexes, [MII2(L2)2(X)4]y+ (M = Mn, Co, Ni, Zn; X = solvent or anion), are formed (bottom right). The cover image was kindly generated by M. Crawford (University of Otago) with Strata Studio Pro (Strata). More details are given by S. Brooker and co‐workers on p. 3772 ff.

Synthesis and characterization of new aromatic poly(ether ketone)s

AbstractA general method for the preparation of aromatic poly(ether ketone)s containing amide, amide‐imide, cyano, oxadiazole, and pyridazine moieties has been developed. Polymerization is based on a ketone‐activated halide displacement from amide‐, amide‐, imide‐, cyano‐, oxadiazole‐, or pyridazine‐containing bis(4‐fluorobenzoyl) moieties by bisphenoxides in a polar aprotic solvent. The bis(4‐fluorobenzoyl) moieties were prepared by reaction of 4‐fluorobenzoyl chloride with diphenoxy monomers containing amide, amide‐imide, cyano, oxadiazole, or pyridazine groups under modified Friedel–Crafts conditions in methylene chloride. All of the polyether ketones prepared were amorphous and exhibited Tgs ranging from 134 to 218°C. In addition, films of the aromatic polyether ketones displayed good thermal stability and flexibility. The dielectric constants of the films were characterized as a function of relative humidity (RH). © 1995 John Wiley &amp; Sons, Inc.