Pyrazolyl Moiety Research Articles

Synthesis and anti H5N1 activities of some novel fused heterocycles bearing pyrazolyl moiety

Ring transformation of the acid hydrazide, derived from 2(3H)-furanone, into triazolopyridazine, triazolothiadiazole, and triazolothiadiazine derivatives, was investigated. The structures of all synthesized compound were demonstrated on the basis of their analytical and spectral data. The antiviral effect of the synthesized compounds against the highly pathogenic avian influenza (HPAI H5N1) was evaluated.

One-pot Synthesis of Novel 2-pyrazolo-3-phenyl-1,3-thiazolidine-4-ones Using DSDABCOC as an Effective Media.

Thiazolidine compounds are known to show interesting pharmacological activity. In particular, they are used as antiseizure, fungicidal, anti-bacterial, antitubercular, antiinflammatory, antiamoebic, anti-diabetic and local anesthetic agents. Some of these compounds have also shown antiparkinsonism, antioxidant, anticonvulsant, hypoglycemic and non-narcotic analgesic activities. On the other hand, pyrazoles have shown antibacterial, antitumor, antiviral, antifungal, anti-tubercular, antiparasitic, anesthetic, anti-diabetic, anti-inflammatory, analgesic and insecticidal activities. In order to improve the pharmacological effects of thiazolidine-4-ones, new pyrazole derivatives have been synthesized. A mixture of pyrazolcarbaldehydes, anilines, thioglycolic acid and DSDABCOC was stirred at room temperature for the required reaction times. The progress of the reaction was monitored by TLC (EtOAc: petroleum ether 1:3). After completion of the reaction as indicated by TLC, the ionic liquid was separated by extraction with 2×15 mL of water. The solid residue was separated by column chromatography. The product was recrystallized from EtOH. The pure products were collected in 82-92% yields. In continuation of our ongoing studies to synthesize heterocyclic and pharmaceutical compounds under mild and practical protocols, we wish to report herein our experimental results on the ultrasound promoted synthesis of 2-pyrazolo-3-phenyl-1,3-thiazolidine-4-ones using various synthesized pyrazolecarbaldehydes, anilines and thioglycolic acid at room temperature. The results illustrated that ionic liquid DSDABCOC certainly improved the yield of the products and reduced the reaction time. In conclusion, we have developed an efficient and simple protocol for the synthesis of novel pyrazolo-1,3-thiazolidine-4-ones using DSDABCOC as an ionic liquid. The easy workup together with the use of inexpensive, reusable and eco-friendly ionic liquid is the notable feature of this novel procedure. To the best of our knowledge, this is the first report of the synthesis of a new library of 1,3-thiazolidine-4-ones bearing a pyrazolyl moiety that enhances the biological activity under solvent-free conditions.

N Donor substituted acetylacetones – versatile ditopic ligands

Abstract Acetylacetone (2,4-pentanedione) derivatives with N donor substituents represent ditopic ligands with coordination sites of distinctly different Pearson hardness. Deprotonation of the acetylacetone (Hacac) moiety leads to O,O′ chelating monoanionic (acac) ligands suitable for coordination to hard cations. The softer N donor site(s) preferably act as nucleophiles towards softer partners. When the organic molecules are employed as linkers and coordinate via either site, they are often selective and allow to synthesize well-ordered heterometallic solids. This review addresses the derivatives of 17 pentanediones with nitrile, pyridyl and pyrazolyl moieties as N donor substituents, with an emphasis on structurally characterized compounds. Depending on the N donor substituents and the cations, O,O′ or N coordination will dominate. The nitrile-substituted compounds essentially behave as acetylacetones; they may easily O,O′ coordinate to a wide range of cations whereas N coordination is limited to AgI, CuI or, in the case of less soft cations, to longer and presumably weaker contacts, e.g. to the more distant sites in Jahn–Teller distorted CuII. In contrast, pyridyl-substituted pentanediones act as N donor ligands, regardless whether their (H)acac site is chelating a cation or not. The still scarcely explored pyrazolyl derivative shows the most complex coordination pattern: it may be deprotonated both at the acetylacetone and the pyrazol site, the latter affording N,N′ bridging ligands. In addition to N donor nucleophilicity, the distance between the alternative coordination sites and their mutual orientation are relevant for crystal engineering applications.

Electron-density distributions in selected ferrocenyl-pyrazolyl late transition-metal complexes.

57Fe Mössbauer spectroscopy has been used to study electronic dispersions in complexes of Fe, Co, Ni and Pd anchored onto 3-ferrocenyl-5-methylpyrazolylmethylenepyridine and 3-ferrocenylpyrazolylmethylenepyridine ligands. Mössbauer spectroscopy shows that pyrazolyl-derivatizing of ferrocene increases the electron-density at the Fe-centre as well as facilitating the Fe to cyclopentadienyl ring back-donation of electron-density. The coordination of the ferrocenyl-pyrazolyl ligand to transition metals such as Fe, Co, Ni and Pd reduces the electron-density at the Fe-centre of the ferrocenyl moiety while increasing the electron-density at the coordinated metal centre, especially in the Fe complexes. The electron-density change at the coordination metal centre is inversely proportional to the electronegativity of the halide substituent. Furthermore, the type of substituent (Me or H) at position 5 on the pyrazolyl moiety has an influence on the electron density at the ferrocenyl-Fe and the coordinated metal centre. The methyl group as a substituent reduces the π-acceptor ability of the pyrazolyl and therefore increases the electron-density at the ferrocenyl-Fe centre. However, when the substituent is hydrogen, the electron-density at the coordination metal centre increases. Similarly, for other metals (i.e., Co, Ni and Pd) the electron density at the ferrocenyl-Fe is also significantly reduced upon coordination of the ligand to the metal. Additionally, Mössbauer experiments reveal a trivalent Fe species in the synthesized complexes which is not discerned by X-ray and elemental analysis. The species has been identified as the oxidative product [Fe(iii)X4]- where X = Cl or Br. The study also highlights and cautions on the possibility of photo-oxidation processes involving both ferrocene and the coordinating Fe-halides under standard lighting conditions with possible contributions from aerated solvents.

Photoluminescent properties of three lanthanide compounds of formulae LnCl3(diphenyl((5-phenyl-1H-pyrazol-3-yl)methyl)phosphine oxide)2, Ln = Sm, Eu and Tb: X-ray structural, emission and vibrational spectroscopies, DFT and thermogravimetric studies

Abstract The synthesis and properties of a new sensitizing bidentate ligand, diphenyl((5-phenyl-1H-pyrazol-3-yl)methyl)phosphine oxide, 2, capable of demonstrating the emissive properties of lanthanide elements, is described. Two ligands are attached to LnCl3 moieties, Ln = Sm, Eu and Tb, resulting in complexes of formulae LnCl3(2)2. These complexes were structurally characterized by single-crystal X-ray crystallography and have geometries that are pentagonal bipyramidal with the two bidentate ligands in a cisoid conformation on the equatorial plane and the three chloride ligands in a mer-configuration. The coordination bond distances decrease from Sm to Tb paralleling the decrease in lanthanide ionic radii. The photoluminescent properties of these complexes were examined and, one of them, TbCl3(2)2, was assessed a ΦF of ca. 1.00. DFT calculations were conducted to understand the mechanism of proton transfer in ligand 2 for a hydrogen atom hopping between nitrogen atoms on the pyrazolyl moiety and, to assess aspects of the coordination sphere of the lanthanide complexes.

Design, Synthesis and Bioactivities of Novel 1,4-Pentadien-3-one Derivatives Containing a Substituted Pyrazolyl Moiety.

In this study, in order to find novel biologically active penta-1,4-dien-3-one derivatives, a series of penta-1,4-dien-3-one compounds containing a substituted pyrazole subunit were designed and synthesized. Their structures were characterized by 1H-NMR, 13C-NMR and elemental analysis. The preliminary bioassays displayed that most of the title compounds showed significant antiproliferative activity against HepG2 cell lines. Especially, compounds 7a–m, o, r, s, u, w, y and z were active against HepG2 cells with IC50 values of 0.10–5.05 μM, which were superior to that of the contrast sorafenib (IC50 = 16.20 μM).

Synthesis of monosubstituted 1,2,4,5-tetrazines – 3-amino-1,2,4,5-tetrazines

The substitution of pyrazolyl moiety in 3-(3,5-dimethyl-1H-pyrazol-1-yl)-1,2,4,5-tetrazine with N-nucleophiles provided a series of highnitrogen tetrazine derivatives, including 2-nitro-1-(1,2,4,5-tetrazin-3-yl)guanidine, N-(1H-tetrazol-5-yl)-1,2,4,5-tetrazin-3-amine, N-(1,2,4,5-tetrazin-3-yl)-1,2,4,5-tetrazin-3-amine, N,N'-di(1,2,4,5-tetrazin-3-yl)-1,2,4,5-tetrazine-3,6-diamine, N-(1,2,4,5-tetrazin-3-yl)-[1, 2, 4]triazolo[4,3-b][1, 2, 4, 5]tetrazin-6-amine, and tritetrazinylamine. The thermal stability of these new compounds was evaluated by differential scanning calorimetry and their energetic characteristics were calculated.

Monoanionic, Bis(pyrazolyl)methylborate [(Ph3B)CH(3,5-(CH3)2Pz)2)]- as a Supporting Ligand for Copper(I)-ethylene, cis-2-Butene, and Carbonyl Complexes.

The monoanionic bidentate ligand [(Ph3B)CH(3,5-(CH3)2Pz)2)]- has been prepared from lithium bis(pyrazolyl)methanide and triphenylborane. This useful new ligand is closely related to the well-established bis(pyrazolyl)borate and bis(pyrazolyl)methane ligands but has key differences to both analogues as well. The ethylene, cis-2-butene, and carbon monoxide adducts [(Ph3B)CH(3,5-(CH3)2Pz)2]Cu(L) (where L = C2H4, cis-CH3HC═CHCH3, and CO) have been prepared from [(Ph3B)CH(3,5-(CH3)2Pz)2)]Li(THF), copper(I) triflate, and the corresponding coligand. These complexes have been characterized by NMR spectroscopy and X-ray crystallography. In all cases the bis(pyrazolyl) moiety is bound in κ2N fashion with the BPh3 group rotated to sit over the metal center, sometimes coordinating to the metal via phenyl carbons as in [(Ph3B)CH(3,5-(CH3)2Pz)2)]Li(THF) and [(Ph3B)CH(3,5-(CH3)2Pz)2]Cu(CO) or simply hovering above the metal site as in [(Ph3B)CH(3,5-(CH3)2Pz)2)]Cu(C2H4) and [(Ph3B)CH(3,5-(CH3)2Pz)2)]Cu(cis-CH3HC═CHCH3). The 13C and 1H resonances of the ethylene carbon and protons of [(Ph3B)CH(3,5-(CH3)2Pz)2)]Cu(C2H4) appear at δ 81.0 and 3.71 ppm in CD2Cl2, respectively. The characteristic CO frequency for [(Ph3B)CH(3,5-(CH3)2Pz)2]Cu(CO) has been observed at υ̅ 2092 cm-1 by infrared spectroscopy and is lower than that of free CO suggesting moderate M → CO π-back-donation. A detailed analysis of these complexes has been presented herein.

The silver(I) complex [HB{3-(CF3),5-(CH3)Pz}3]AgNCCH3 supported by a partially fluorinated scorpionate ligand.

Tris(pyrazolyl)borates are used extensively in metal coordination chemistry and belong to a class of ligands generally referred to as scorpionates. The steric and electronic properties of these ligands can be modified quite easily by varying the substituents on the 3-, 4-, and 5-positions of the pyrazolyl moieties on the B atom. Fluorinated tris(pyrazolyl)borates are useful in the stabilization of rare silver(I) complexes. The silver(I) adduct (acetonitrile-κN){tris[5-methyl-3-(trifluoromethyl)pyrazol-1-yl-κN2]hydroborato}silver(I), [Ag(C15H13BF9N6)(CH3CN)] or [HB{3-(CF3),5-(CH3)Pz}3]AgNCCH3, was obtained by treating [HB{3-(CF3),5-(CH3)Pz}3]Na with CF3SO3Ag in the presence of acetonitrile, and was isolated in 85% yield. Single-crystal X-ray diffraction analysis reveals that the AgI center has a pseudo-tetrahedral all-nitrogen coordination sphere, and is supported by a tris(pyrazolyl)borate ligand that binds to the AgI center in a κ3-fashion.

Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of new 1-phenylpyrazolo[3,4-d]pyrimidine derivatives

A new group of 1-phenylpyrazolo[3,4-d]pyrimidine derivatives 14a–d–21 were synthesized from 2-(6-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)acetohydrazide (12). All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, anti-inflammatory activity and ulcerogenic liability. All the target compounds were more potential in inhibiting COX-2 than COX-1. Compounds having pyrazolyl moiety in a hybrid structure with pyrazolo[3,4-d]pyrimidine scaffold (14a–d, 16 and 17) showed higher edema inhibition percentage activities (34–68%) and the 5-aminopyrazole derivative (14c, ED50 = 87.9 μmol/kg) was the most potent one > celecoxib (ED50 = 91.9 μmol/kg). While, the in vivo potent compounds (14a–d, 16, 17 and 21) caused variable ulceration effect (ulcer index = 0.33–4.0) comparable to that of celecoxib (ulcer index = 0.33), the pyrazol-3-one derivative (16) and the acetohydrazide (21) were the least ulcerogenic derivatives showing the same ulcerogenic potential of celecoxib.

Novel pyrazole derivatives with oxa/thiadiazolyl, pyrazolyl moieties and pyrazolo[4,3-d]-pyrimidine derivatives as potential antimicrobial and anticancer agents

A series of [4-amino-3-(4-chlorophenyl)-1H-pyrazol-5-yl](3,5-dimethyl-1H-pyrazol-1-yl)-methanone and 6-amino-3-(4-chlorophenyl)-5-methyl-1,6-dihydro-7H-pyrazolo[4,3-d]-pyrimidin-7-one have been synthesized from ethyl 4-amino-3-(4-chlorophenyl)-pyrazol-5-carboxylate. The newly synthesized compounds were characterized by IR, 1H NMR, 13CNMR, Mass spectra and Elemental analysis. The compounds were evaluated for their in vitro antimicrobial and anticancer activity. Among the synthesized compounds, compounds 7a,b and 15 exhibited higher anticancer activity than the doxorubicin as reference drug. Most of the newly synthesized compounds have good to excellent antimicrobial activity.

Synthesis, structure, antibacterial studies and DFT calculations of arene ruthenium, Cp∗Rh, Cp∗Ir and tricarbonylrhenium metal complexes containing 2-chloro-3-(3-(2-pyridyl)pyrazolyl)quinoxaline ligand

The ligand [2-chloro-3-(3-(2-pyridyl)pyrazolyl)quinoxaline] (L) have been prepared from 2,3-dichloroquinoxaline and 3-(2-pyridyl)-1H-pyrazole. The reaction of N,N′-bidentate chelating ligand (L) and the corresponding metal precursors [(arene)Ru(μ-Cl)Cl]2 {arene=p-cymene, benzene, hexamethylbenzene (HMB)}, [Cp∗M(μ-Cl)Cl]2 {Cp∗=pentamethylcyclopentadiene; M=Rh, Ir}, [CpRuCl(PPh3)2] {Cp=cyclopentadiene; PPh3=triphenylphosphine} and [Re(CO)5Br] leads to the formation of mononuclear metal complexes having the general formula [(arene)Ru(L)Cl]+ where, arene=p-cymene (1), C6H6 (2), C6Me6 (3), [Cp∗M(L)Cl]+ where, M=Rh (4), Ir (5), [CpRu(L)PPh3]+ (6) and [Re(L)(CO)3Br] (7). All these platinum group metal complexes were synthesized and isolated with PF6 counter anions except complex (6) whereas the complex (7) was isolated as a neutral complex. All these metal complexes were fully characterized by FT-IR, 1H NMR, UV–Vis and mass spectroscopic and analytical techniques. Moreover, the complexes (1–7) were determined by the single-crystal X-ray diffraction analysis. Single crystal X-ray data confirms that the coordination occurs to the N-atoms of the pyridyl and pyrazolyl moieties of the ligand. Agar well diffusion method reveals that complexes (1, 2, 4 and 5) are having good antibacterial activity against the three different bacteria, pathogenic test organisms Staphylococcus aureus subsp. aureus, Staphylococcus epidermidis and Escherichia coli. The electronic transitions and absorption band of the complexes calculated by using time-dependent DFT method are in good agreement with the experimental results.

Synthesis, characterization and in vitro antimicrobial evaluation of some novel hydrazone derivatives bearing pyrimidinyl and pyrazolyl moieties as a promising heterocycles

In the present investigation, ten new 2-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-1-(4,6-dimethylpyrimidin-2-yl)hydrazine (3a–j) having pyrimidinyl and pyrazolyl moieties were synthesized. Structures of all compounds were confirmed by their spectral and elemental data. Most of the tested compounds were found to be significantly more effective against bacterial strains Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa than the reference drug ciprofloxacin. All the newly synthesized compounds were found to be more potent antifungal agents than reference drug against Candida albicans, whereas except 3e all other compounds also shown good activity against Saccharomyces cerevisiae.

N-Donor Competition in Iron Bis(chelate) Bis(pyrazolyl)pyridinylmethane Complexes

Abstract We report on the synthesis and structural characterisation of the bis(chelate) bis(pyrazolyl) pyridinylmethane iron(II) complexes [Fe{HC(Pz)2(Py)}2][CF3CO2]2, [Fe{HC(3-iPrPz)(5- iPrPz)(Py)}2][CF3SO3]2 and [Fe{HC(3-iPrPz)(5-iPrPz)(Py)}2][FeBr4]Br·2C4H8O. During the synthesis of the latter ones, an isomerisation of the ligand is observed: the pyrazolyl substituent formally moves from the 3 to the 5 position. Since the donor competition between pyrazolyl and pyridinyl moieties is important for the coordination properties, we also studied the donor properties by density functional theory and natural bond orbital analysis (NBO). As a result, the pyridinyl donor is generally weaker than the pyrazolyl donor, but the pyrazolyl donor is heavily influenced by the alkyl substitution pattern. To confirm the low-spin state of the complexes, magnetic susceptibility measurements have been performed

A Versatile Protocol for the Synthesis of Pyrazolyl‐Substituted Pyridinium and Guanidinium Salts from Pyridone and Urea Derivatives

AbstractThe trication (pyr3P2)3+ (1+, pyr = 3,5‐dimethylpyrazolyl) is used as a convenient pyrazolyl‐transfer reagent to convert 2‐pyridones, 4‐pyridones, and urea derivatives to pyrazolyl‐substituted pyridinium or guanidinium triflate salts. This conversion represents a new, efficient, and highly functional‐group‐compatible approach that yields the desired products conveniently and in high yields. Typically, this reaction proceeds by exchange of the carbonyl oxygen atom of the substrate for a pyrazolyl moiety. However, for the structurally related 3‐hydroxypyridines, a different reaction pathway occurs to give tripyridyl phosphites. The outcome of the reaction can be explained by the lactam–lactim tautomerism of the substrate and is discussed in detail. All reaction products were fully characterized by elemental analysis and multinuclear NMR, IR, and Raman spectroscopy, and the structural arrangements of most of the products were confirmed by X‐ray crystallography analysis.

Synthesis, Characterization and Antitumor Activity of Novel Ferrocene-Based Amides Bearing Pyrazolyl Moiety

A series of novel ferrocene-based amides bearing pyrazolyl moiety (4a–4q) were synthesized in good yields and their antitumor activities were evaluated. Their structures were characterized by 1H NMR, 13C NMR and elemental analysis. The crystal structures of compounds 4i and 4q were confirmed by X-ray crystallographic analysis. Further biological results demonstrated that most of the compounds reported herein exhibited potent antitumor activities against Smmc7721 and SGC7901 cancer cell lines. Among them, compound 4o is the most potent one with an IC50 value of 9.84 μg/mL against SGC7901 cell line, providing us a template for further development.

Structure-Activity Relationship of Diacylhydrazine Derivatives Fluoride-Containing Pyrazolyl Moiety

In search of novel bioactive compounds, 19 compounds were designed and synthesized by introducing the fluoropyrazolyl pharmacophore into the diacylhydrazine scaffold by Zhang et al. and others. The herbicidal activities of these compounds were evaluated. The bioassay results showed that most of them exhibited higher herbicidal activities against dicotyledonous weeds (Abutilon theophrasti, Amaranthus ascedense and Amaranthus retroflexus) than monocotyledonous weeds. The quantum study of diacylhydrazine derivatives fluoridecontaining pyrazolyl moiety was calculated by Gaussian 03 program. The study found the correlation between the herbicidal activity of these compounds and structural parameters and filter the main factors to affect the biological activity and the influence to biological activity from the changes in the molecular structure was explained, the mechanism and sites of action of compound was also discussed.

New pyrazolyl and thienyl aminohydantoins as potent BACE1 inhibitors: Exploring the S2′ region

The proteolytic enzyme β-secretase (BACE1) plays a central role in the synthesis of the pathogenic β-amyloid in Alzheimer's disease. SAR studies of the S2' region of the BACE1 ligand binding pocket with pyrazolyl and thienyl P2' side chains are reported. These analogs exhibit low nanomolar potency for BACE1, and demonstrate >50- to 100-fold selectivity for the structurally related aspartyl proteases BACE2 and cathepsin D. Small groups attached at the nitrogen of the P2' pyrazolyl moiety, together with the P3 pyrimidine nucleus projecting into the S3 region of the binding pocket, are critical components to ligand's potency and selectivity. P2' thiophene side chain analogs are highly potent BACE1 inhibitors with excellent selectivity against cathepsin D, but only modest selectivity against BACE2. The cell-based activity of these new analogs tracked well with their increased molecular binding with EC(50) values of 0.07-0.2 μM in the ELISA assay for the most potent analogs.

ChemInform Abstract: Synthesis and Photodynamic Activities of Pyrazolyl and Cyclopropyl Derivatives of Purpurin‐18 Methyl Ester and Purpurin‐18‐N‐butylimide.

AbstractNew purpurin‐18 methyl ester and purpurin‐18‐N‐butylimide derivatives incorporating cyclopropyl or pyrazolyl moieties are synthesized.

Mononuclear non-heme iron(III) complexes of linear and tripodal tridentate ligands as functional models for catechol dioxygenases: Effect of N-alkyl substitution on regioselectivity and reaction rate

Catechol dioxygenases are responsible for the last step in the biodegradation of aromatic molecules in the environment. The iron(II) active site in the extradiol-cleaving enzymes cleaves the C–C bond adjacent to the hydroxyl group, while the iron(III) active site in the intradiol-cleaving enzymes cleaves the C–C bond in between two hydroxyl groups. A series of mononuclear iron(III) complexes of the type [Fe(L)Cl3], where L is the linear N-alkyl substituted bis(pyrid-2-ylmethyl)amine, N-alkyl substituted N-(pyrid-2-ylmethyl)ethylenediamine, linear tridentate 3N ligands containing imidazolyl moieties and tripodal ligands containing pyrazolyl moieties have been isolated and studied as structural and functional models for catechol dioxygenase enzymes. All the complexes catalyse the cleavage of catechols using molecular oxygen to afford both intra- and extradiol cleavage products. The rate of oxygenation depends on the solvent and the Lewis acidity of iron(III) center as modified by the sterically demanding N-alkyl groups. Also, our studies reveal that stereo-electronic factors like the Lewis acidity of the iron(III) center and the steric demand of ligands, as regulated by the N-alkyl substituents, determine the regioselectivity and the rate of dioxygenation. In sharp contrast to all these complexes, the pyrazole-containing tripodal ligand complexes yield mainly the oxidized product benzoquinone. The steric demand of coordinated ligand donors and the Lewis acidity of the iron(III) center, as regulated by the N-alkyl subtituents on the central and terminal N-atoms, determine the catechol cleavage yields and the rate of dioxygenation. Especially, the sterically demanding and weakly coordinating -CH2N(R1)(R2) arm enhances the extradiol-to-intradiol product selectivity.