Phenoxy Moiety Research Articles

Schiff‐Base Aluminum Complexes as Bifunctional Catalysts for the Selective Ring‐Opening Co‐Polymerization of Cyclohexene Oxide and Succinic Anhydride

AbstractThe ring‐opening copolymerization (ROCOP) of epoxides and cyclic anhydrides is emerging as a powerful method for the synthesis of polyesters with innovative structures and properties. In this work, a series of dialkyl‐aluminum complexes stabilized by Schiff‐base ligands with different functional side arms (pyridine, amine, or phosphine) and different substituents on the phenoxy moieties have been synthetized and tested as catalysts in the ROCOP of cyclohexene oxide (CHO) and succinic anhydride (SA). The selectivity of the catalysts in the ROCOP was significatively depending on the nature of the pendant arm and/ or of the substituents of the ligand framework. The complexes designed to have a dynamic coordination sphere in which the side arms simulate the role of a neutral cocatalyst favored the desired selectivity, giving poly(CHO‐alt‐SA) with narrow dispersity and negligible ether linkage. NMR investigations and DFT calculations rationalized the observed behavior.

Novel phenoxyacetylthiosemicarbazide derivatives as novel ligands in cancer diseases

Numerous epidemiological studies report an increased risk of developing prostate cancer in patients with melanoma and an increased risk of developing melanoma in patients with prostate cancer. Based on our previous studies demonstrating the high anticancer activity of thiosemicarbazides with a phenoxy moiety, we designed nineteen phenoxyacetylthiosemicarbazide derivatives and four of them acting as potential dual-ligands for both cancers. All of the compounds were characterized by their melting points and 1H, 13C NMR and IR spectra. For selected compounds, X-ray investigations were carried out to confirm the synthesis pathway, identify the tautomeric form and intra- and intermolecular interaction in the crystalline state. The conformational preferences and electronic structure of molecules were investigated by theoretical calculation method. Lipophilicity of compounds (log kw) was determined using isocratic reversed phase/high pressure liquid chromatography RP-18. For the obtained compounds, in vitro tests were carried out on four melanoma cell lines (A375, G-361, SK-MEL2, SK-MEL28), four prostate cancer cell lines (PC-3, DU-145, LNCaP, VcaP) and a normal human fibroblast cell line (BJ). The most active compounds turned out to be F6. Cell cycle analysis, apoptosis detection, CellROX staining and mitochondrial membrane potential analysis were performed for the most sensitive cancer cells treated with most active compounds. DSC analysis was additionally performed for selected compounds to determine their purity, compatibility, and thermal stability. The process of prooxidation was proposed as a potential mechanism of anticancer activity.

Terminal Phenoxy Group as a Privileged Moiety of the Drug Scaffold-A Short Review of Most Recent Studies 2013-2022.

The terminal phenoxy group is a moiety of many drugs in use today. Numerous literature reports indicated its crucial importance for biological activity; thus, it is a privileged scaffold in medicinal chemistry. This review focuses on the latest achievements in the field of novel potential agents bearing a terminal phenoxy group in 2013–2022. The article provided information on neurological, anticancer, potential lymphoma agent, anti-HIV, antimicrobial, antiparasitic, analgesic, anti-diabetic as well as larvicidal, cholesterol esterase inhibitors, and antithrombotic or agonistic activities towards the adrenergic receptor. Additionally, for selected agents, the Structure–Activity–Relationship (SAR) is also discussed. Thus, this study may help the readers to better understand the nature of the phenoxy group, which will translate into rational drug design and the development of a more efficient drug. To the best of our knowledge, this is the first review devoted to an in-depth analysis of the various activities of compounds bearing terminal phenoxy moiety.

Corybungines A−K: Isoquinoline alkaloids from Corydalis bungeana with dopamine D2 receptor activity

Eleven undescribed isoquinoline alkaloids corybungines A−K including a protoberberine-type alkaloid, an isoquinoline alkaloid with a unique 6-norprotoberberine skeleton, one 13,14-seco-protoberberine-type alkaloid, two 1a,14-seco-protoberberine-type alkaloids with a 4-(hydroxymethyl)phenoxy moiety and six aporphine alkaloids, together with seven known alkaloids, have been isolated from the whole herb extract of Corydalis bungeana Turcz. Their structures and absolute configurations were elucidated based on an analysis of spectroscopic data and electronic circular dichroism (ECD) spectra. (R)-stephanine displayed high antagonistic activity against the dopamine D2 receptor with an IC50 value of 0.85 ± 0.09 μM in CHO-D2 cells. Additionally, corybungines D, F, H, (R)-roemerine, (R)-vireakine and (R)-tuduranine showed moderate D2 antagonism (IC50 5.20–26.07 μM). The preliminary structure-activity relationships (SARs) of aporphine alkaloids were discussed.

Cyanophenoxy-Substituted Silicon Phthalocyanines for Low Threshold Voltage n-Type Organic Thin-Film Transistors

Silicon phthalocyanines (SiPcs) are a class of n-type or ambipolar organic semiconductors that have been incorporated into organic thin-film transistors (OTFTs), organic light-emitting diodes (OLEDs), and organic photovoltaics (OPVs). Despite a relatively large catalogue of previously reported SiPc materials, fabricated OTFTs with these materials typically have threshold voltages (VT) above 10 V, limiting their usage in commercial devices due to exceedingly high power consumption. Recent studies have suggested that the VT can be reduced in OTFTs prepared from phenoxy-substituted SiPcs by introducing electron-withdrawing groups onto the phenoxy moieties. Herein, we report the synthesis and characterization of three SiPcs with phenoxy axial substituents containing nitrile and fluorine functional groups. These SiPcs, along with 3,5-difluorophenoxy SiPc were evaluated as candidate materials for n-type OTFTs. We found that further increasing the electron-withdrawing character of the pendant phenoxy groups of the SiPc resulted in a significant decrease in average VT with the lowest reported value being 4.8 V, the lowest VT reported for a phenoxy-SiPc-based OTFT exceeding the previous record low of 7.8 V attributed to F10-SiPc. This decrease in VT could be directly correlated to the Hammett parameter of the axial functional groups. Furthermore, it was noted that dewetting occurred when the phenoxy pendant group of the SiPc was substituted at the para position with a nitrile group combined with ortho- or meta-substituted fluorines, which was attributed to interactions at the semiconductor/dielectric interface. Depositing these SiPcs on silane-terminated poly(styrene) brush modified substrates improved long-term stability, demonstrated by a minimal change in surface morphology according to atomic force microscopy (AFM) images.

Design, synthesis, antitrypanosomal activity, DNA/RNA binding and invitro ADME profiling of novel imidazoline-substituted 2-arylbenzimidazoles.

Novel imidazoline benzimidazole derivatives containing diversely substituted phenoxy moieties were synthesized with the aim of evaluating their antitrypanosomal activity, DNA/RNA binding affinity and invitro ADME properties. The presence of the diethylaminoethyl subunit in 18a-18c led to enhanced antitrypanosomal potency, particularly for 18a and 18c, which contain unsubstituted and methoxy-substituted phenoxy moieties. They were found to be>2-fold more potent against African trypanosomes than nifurtimox. Fluorescence and CD spectroscopy, thermal denaturation assays and computational analysis indicated a preference of 18a-18c toward AT-rich DNA and their minor groove binding mode. Replacement of the amidine group with less basic and ionisable nitrogen-containing moieties failed to improve membrane permeability of the investigated compounds. Due to structural diversification, the compounds displayed a range of physico-chemical features resulting in variable invitro ADME properties, leaving space for further optimization of the biological profiles.

Nonlinear optical properties of peripheral symmetrically and non-symmetrically 4-(trifluoromethoxy)phenoxy substituted zinc phthalocyanines

In this work, new non-symmetrical, peripherally substituted metallophthalocyanines, namely 2(3)-[(4-nitrophenyl)ethynyl]-{9,10,16,17,23,24-hexakis-(4-(trifluoromethoxy)phenoxy)-phthalocyaninato}zinc (1b) and 2(3)-[(4-nitrophenyl)ethynyl]-{9(10),16(17),23(24)-tris-(4-(trifluoromethoxy)phenoxy)-phthalocyaninato}zinc (2b) were prepared. Structural elucidation of the novel zinc phthalocyanines was carried out with well-known spectroscopic methods. The solubility of the phthalocyanines was investigated in organic solvents like tetrahydrofuran, dichloromethane, and dimethyl sulfoxide. The effect of concentration on aggregation behavior of the resulting phthalocyanines (1b and 2b) was examined in a wide area ranging from 4 × 10−6 to 14 × 10−6 M in tetrahydrofuran. Aggregation properties of the macrocyclic molecules (1b and 2b) were also investigated in many organic solvents. Based on the data existing in the literature, peripherally octa- and tetra-substituted zinc phthalocyanines (1a and 2a) with 4-(trifluoromethoxy)phenoxy moieties were synthesized. Optical limiting and the third-order nonlinear properties of symmetrically and non-symmetrically substituted phthalocyanines were determined and compared with each other.

O‐Trityl phenoxy‐imino vanadium (III) complexes: synthesis, characterization, and catalysis on ethylene (co)polymerization

Several phenoxy‐imine ligands bearing o‐trityl group in phenoxy moiety RN=CHArOH (Ar = C6H2(CPh3)tBu, R = 2,6‐Me2C6H3 (L1H); 2,6‐iPr2C6H3 (L2H); 3,5‐(CF3)2C6H3 (L3H); 3,5‐(OMe)2C6H3 (L4H); CHPh2 (L5H); CPh3 (L6H)) were synthesized and characterized by1H NMR and 13C NMR spectroscopy. The vanadium complexes based on these ligands LVCl2(THF)2 (1–6) were synthesized via conventional transmetalation reaction in moderate to high yields. Complexes 1–6 were fully characterized by FT‐IR, elemental analyses and the molecular structures of 1, 2·H2O, (2·H2O)2(μ‐Cl)2, 4, and 5 were confirmed by X‐ray crystallographic analysis in which the six‐coordinated vanadium centers are in a typical octahedral geometry. Upon activation with Et2AlCl in toluene, complexes 1–6 showed high activities in ethylene polymerization affording polymers with moderate molecular weight (5.9–11.8 × 104 Da). Moreover, in hexane or CH2Cl2, 1–6/Et2AlCl exhibited enhanced activities. When activated with MAO or MMAO in toluene, these complexes showed relatively low activities but afforded polymers with ultra‐high molecular weight (up to 3.30 × 106 Da). 1–6/Et2AlCl also showed high activities in ethylene/1‐hexene copolymerization at room temperature giving moderate molecular‐weight polymers (6.5–11.4 × 104 Da) with co‐monomer incorporation being of 6.0 ~ 7.8%.

Keteniminium Salts as Key Intermediates for the Efficient Synthesis of 3‐Amino‐Indoles and ‐Benzofurans

AbstractHerein, we describe a high yielding approach towards the synthesis of 3‐amino‐indoles and ‐benzofurans through 6π‐electrocyclization. This was made possible by taking advantage of the high reactivity of keteniminium salts, formed in‐situ by treating with triflic anhydride and 2‐fluoropyridine amides bearing at the α‐position either an aniline or a phenoxy moiety. These mild conditions, on top of furnishing rapidly the 3‐aminobenzoheteroles, allow the tolerance of various functional groups. Control experiments were carried out to highlight that the keteniminium is, indeed, in most cases, the reactive intermediate and conformational preferences of such species were investigated through a DFT study.

Synthesis, characterization, and investigation of photochemical properties of tetra-substituted zinc phthalocyanines bearing 4-(3,5-dimethyl-1H-pyrazol-1-yl)phenyl moiety with different linker heteroatoms

A novel 4-((3,5-dimethyl-1H-pyrazol-1-yl)phenylthio)phthalonitrile 3 and corresponding zinc phthalocyanine 5 has been synthesized and characterized. There has been investigated the effect of nature of the linker heteroatom (S or O) on spectroscopic, photophysical and photochemical properties of zinc phthalocyanine 5 and zinc phthalocyanine 6, containing 4-(3,5-dimethyl-1H-pyrazol-1-yl)phenoxy moiety. The zinc phthalocyanines 5 and 6 are highly soluble in common organic solvents. The solvatochromic effects were evaluated by changes in UV–Vis spectra. A correlation between the Q band frequency and the refractive index of 20 organic solvents was examined. The aggregation behavior and photochemical properties (quantum yields singlet oxygen generation and photodegradation) of zinc phthalocyanines were investigated at different concentrations in DMSO, DMF, THF and water-organic solvents mixtures. The water content in the mixture has a crucial effect on the aggregation behavior and the generation of singlet oxygen. In DMSO aggregation of 5 takes place with the addition of any amount of water, whereas for 6 the formation of dimers is observed at a water concentration of more than 10%. However, in THF the formation of aggregates is observed at a water concentration above 30% for 5 and 50% for 6. The synthesized novel phthalocyanines have high quantum yield of singlet oxygen (ΦΔ) values (the range of 0.50–0.70) and can be considered as potential photosensitizers for photodynamic therapy. The highest ΦΔ values were obtained for zinc phthalocyanine 6 containing oxygen linker heteroatom in all solvents.

Imidodiphosphonate Ligands for Enhanced Sensitization and Shielding of Visible and Near-Infrared Lanthanides.

The design of coordination sites around lanthanide ions has a strong impact on the sensitization of their luminescent signal. An imidodiphosphonate anionic binding site is attractive as it can be functionalized with "remote" sensitizer units, such as phenoxy moieties, namely, HtpOp, accompanied by an increased distance of the lanthanide from the ligand high-energy stretching vibrations which quench the luminescence signal, hence providing flexible shielding of the lanthanide. We report the formation and isolation of Ln(tpOp)3 complexes where Ln = Er, Gd, Tb, Dy, Eu, and Yb and the Y(tpOp)3 diamagnetic analogue. The complexes are formed from reaction of KtpOp and the corresponding LnCl3·6H2O salt either by titration and in situ formation or by mixing and isolation. All complexes are seven-coordinated by three tpOp ligand plus one ethanol molecule, except for Yb(tpOp)3 which has no solvent coordinated. Phosphorus NMR shows characteristic shifts to support the coordination of the lanthanide complexes. The complexes display visible and near-infrared luminescence with long lifetimes even for the near-infrared complexes which range from 3.3 μs for Nd(tpOp)3 to 20 μs for Yb(tpOp)3. The ligand shows more efficient sensitization than the imidodiphosphinate analogues for all lanthanide complexes with a notable quantum yield of the Tb(tpOp)3 complex at 45%. We attribute this to the properties of the remote sensitizer unit and its positioning further away from the lanthanide, eliminating quenching of high energy C-H vibrations from the ligand shell. Calculations of the ligand shielding support the photophysical properties of the complexes. These results suggest that these binding sites are promising in the further development of the lanthanide complexes in optoelectronic devices for telecommunications and new light emitting materials.

Comparative study of multi-functional luminogens with 1,3,5-triazine as the core and phenothiazine or phenoxy donors as the peripheral moieties for non-doped/doped fluorescent and red phosphorescent OLEDs

A series of three-armed fluorescent emitters based on a 1,3,5-triazine acceptor as the central core and phenothiazine or phenoxy moieties as the different peripheral units, are designed and synthesized. All of them exhibit aggregation-induced emission enhancement and thermally activated delayed fluorescence. Photoluminescence quantum yields exceeded 37 and 67% for non-doped and doped solid-state samples respectively. The compounds were found to be capable of transporting both holes and electrons. The highest mobility values of more than 1 × 10−4 cm2V−1s−1 were obtained for the compound having three phenothiazine moieties at electric field of more than 1 × 106 Vcm−1. Additionally, three types of organic light emitting diodes based on these materials were fabricated. The device containing non-doped emission layer with the compound containing single phenothiazine moiety as the emitter gave maximum external quantum efficiency of 5.4%. The device with doped emission layer containing 5% solid solution of the compound having three phenothiazine moieties in an appropriate host gave maximum external quantum efficiency of 9.9%. The phosphorescent device hosted by the compound with single phenothiazine unit exhibited maximum external quantum efficiency of 10.3% and a low-efficiency roll-offs of 1% at 1000 cd/m2.

Ecotoxicity of ammonium chlorophenoxyacetate derivatives towards aquatic organisms: Unexpected enhanced toxicity upon oxygen by sulfur replacement

Phenoxyacetate herbicides, such as 2,4-D and MCPA, having a high toxicity to non-target organisms are commonly used for controlling broadleaf weeds in agriculture. However, novel and environmentally friendly analogs are constantly sought after. For this purpose, various substituents at the phenyl group have been tested to find the optimal balance between the potent herbicidal activity and safety for non-target species. In this work, we investigated the influence of the oxygen by sulfur replacement in the phenoxy moiety of ammonium chlorophenoxyacetates on the toxicity towards aquatic organisms, such as bacteria (Vibrio fischeri), water flea (Daphnia magna) and freshwater fish (Pimephales promelas) by determining experimental (Microtox® test – V. fischeri) and predicted (ACD Lab Percepta software – D. magna, P. promelas) EC50/LC50 values. The achieved results showed that in contrary to the literature observations, where O-compounds were more toxic than their S-analogs (urea/thiourea), the O/S replacement in chlorophenoxyacetate significantly increased ecotoxicity of the S-analogs (up to 11 times). Moreover, one- and two-substituted phenoxyacetates in the form of ammonium salts were less toxic to V. fischeri than the commercially available phenoxy herbicides in the acid form. The logP/logD values were also calculated to understand hydro/lipophilic nature of the investigated compounds and differences in their toxicity.

Variations in the Solid‐State Emissions of Clothespin‐Shaped Binuclear trans‐Bis(salicylaldiminato)platinum(II) with Halogen Functionalities

The syntheses, aggregation motifs and solid‐state emissions of clothespin‐shaped binuclear trans‐bis(salicylaldiminato)platinum(II) complexes 1–4 bearing halogen atoms (X) at the para positions of phenoxy moieties are described and compared with those of the non‐substituted analog 5. Crystalline (±)‐4 (X = I, polymorph B) obtained by recrystallization from benzene exhibits intense phosphorescent emission under UV irradiation at ambient temperature, while crystals of (±)‐1 (X = F), (±)‐2 (X = Cl), (±)‐3 (X = Br) and (±)‐4 (X = I, polymorph A), obtained from poor solvents including hexanes, are less emissive under the same conditions. The emission intensities of these crystals increase in the order of (±)‐4 (B) > (±)‐5 > (±)‐1–3, (±)‐4 (A). XRD analysis shows that the less emissive crystals (±)‐1–3 and (±)‐4 (polymorph A) form specific aggregates in which (R)‐ and (S)‐units with “A”‐shaped conformations are aligned in an alternating, shuttlecock‐like interpenetrating manner as a result of one‐dimensional infinite X⋯π interactions. The emissive polymorph 4 (B) exhibits a significantly different non‐interpenetrating alignment of “A”‐shaped conformational units, which are firmly bound as a result of a two‐dimensional constraint network consisting of I⋯I and Pt⋯Pt interactions. The present variations in solid‐state emission are therefore explained on the basis of the constraint dimensionality of the packing units of each complex.

Synthesis, characterization and photovoltaic behaviours of peripheral and non-peripheral tetra-[4-(4-octylpiperazin-1-yl)phenoxy] substituted zinc(II), cobalt(II), copper(II) and indium(III) phthalocyanines

The synthesis of zinc(II), cobalt(II), copper(II) and indium(III)(OAc) phthalocyanines carrying four 4-(4-octylpiperazin-1-yl)phenoxy moieties in peripheral/non-peripheral positions were performed by the cyclotetramerization of compounds 4-[4-(4-octylpiperazin-1-yl)phenoxy]phthalonitrile or 3-[4-(4-octylpiperazin-1-yl)phenoxy]phthalonitrile with respective metal salts. The novel phthalonitriles and phthalocyanines were characterized by elemental and spectroscopic analysis, including 1H NMR, 13C NMR, FT-IR, UV–Vis spectral and MALDI-TOF mass data. To clarify the influence of the position of substituent group and the variety of the central metal atom on the photovoltaic performance, bulk heterojunction devices by using phthalocyanines with different blend ratio, as donor was fabricated and characterized.

Phenoxyimine Ligands Bearing Nitrogen-Containing Second Coordination Spheres for Zinc Catalyzed Stereoselective Ring-Opening Polymerization of rac-Lactide

A series of zinc (Zn1–Zn6) and aluminum (Al6) complexes supported by phenoxyimine ligands (L1–L6) bearing nitrogen-containing second coordination spheres were synthesized and investigated for ring-opening polymerization (ROP) of rac-lactide (rac-LA). The ligands L1–L4 and L6 bearing sterically opened nitrogen donors resulted in dynamic NNO-chelates associated with facile nitrogen–metal coordination interactions. The bulky ligand L5 resulted in L2Zn-type complex Zn5 by disproportionation. The zinc complexes exhibited catalytic activities in ROP of cyclic monomers, including rac-LA, e-caprolactone (CL), δ-valerolactone (VL), and trimethylene carbonate (TMC). The zinc complex Zn6 bearing a bulky triphenylsilyl substituent at the 3-position of the phenoxy moiety exhibited good stereochemical control during the ROP of rac-LA to produce highly heterotactic PLAs at ambient temperature (Pr = 0.90) as well as low temperature (−30 °C, Pr = 0.94) with narrow molecular weight distributions (Mw/Mn < 1.2). The aluminum...

Multitarget 1,4-Dioxane Compounds Combining Favorable D2-like and 5-HT1A Receptor Interactions with Potential for the Treatment of Parkinson's Disease or Schizophrenia.

The effect of methoxy and hydroxy substitutions in different positions of the phenoxy moiety of the N-((6,6-diphenyl-1,4-dioxan-2-yl)methyl)-2-phenoxyethan-1-amine scaffold on the affinity/activity for D2-like, 5-HT1A, and α1-adrenoceptor subtypes was evaluated. Multitarget compounds with suitable combinations of dopaminergic and serotoninergic profiles were discovered. In particular, the 2-methoxy derivative 3 showed a multitarget combination of 5-HT1A/D4 agonism and D2/D3/5-HT2A antagonism, which may be a favorable profile for the treatment of schizophrenia. Interestingly, the 3-hydroxy derivative 8 behaved as a partial agonist at D2 and as a potent full agonist at D3 and D4 subtypes. In addition to its potent 5-HT1A receptor agonism, such a dopaminergic profile makes 8 a potential multitarget compound for the treatment of Parkinson's disease (PD). Indeed, the activation of 5-HT1A receptors might be helpful in reducing dyskinetic side effects associated with dopaminergic stimulation.

Comparative Electrochemistry and Electrochromic Application of Novel Binuclear Double‐Decker Rare Earth Metal Phthalocyanines Bearing 4-(hydroxyethyl)phenoxy Moieties

In the present work, novel double-decker samarium(III), europium(III), and ytterbium (III) phthalocyanines (SmPc2, EuPc2, and YbPc2) bearing 4-(hydroxyethyl)phenoxy moieties have been synthesized and their electrochemical redox, spectroelectrochemical, and electrocolorimetric properties of the complexes have been inquired comparatively in two different non-aqueous solution. All complexes were observed to expose a series of usually reversible phthalocyanine ring-based one-electron reduction and oxidation processes. The effect of the size of rare earth metal ion was clearly reflected as the modest shift in half-wave potentials. Enriched electron transfer processes of the complexes and the interaction between the electrochemically generated anionic and cationic species caused distinct spectral and color changes, identified with in-situ spectroelectrochemical and in-situ electrocolorimetric measurements in solution medium. Spectroelectrochemical and electrocolorimetric measurements of the complexes were also performed in the solid state as the Langmuir-Blodgett film on an indium tin oxide glass in order to understand their technological applicability in electrochromic devices as color changing material. Comparative evaluation of these measurements suggested that Langmuir-Blodgett films of SmPc2 and EuPc illustrate highly reversible distinct color change from green to purple with satisfying electrochromic performance for electrochromic device applications.

Effect of gold nanoparticles shape and size on the photophysicochemical behaviour of symmetric and asymmetric zinc phthalocyanines

Glutathione (GSH) capped Au nanotriangles (AuNTs–GSH) and nanospheres (AuNSs–GSH) are covalently linked to symmetric Zn phthalocyanine (ZnPc) substituted with phenoxy propanoic acid substituents only (complex 1) and two asymmetric ZnPc, each containing one phenoxy propanoic acid and three benzothiazole phenoxy moieties (complex 2), and one phenoxy propanoic acid and no other ligands (complex 3). The photophysicochemical behaviour of Pc complexes and their conjugates were studied. All conjugates displayed improved triplet and singlet oxygen quantum yields with decreases in fluorescence quantum yields compared to their respective Pc complexes. The conjugates of asymmetric complexes 2 and 3, afforded much higher triplet and singlet oxygen quantum yields compared to the symmetric complex 1, and could serve as good candidates for photodynamic therapy.

Synthesis, Nematicidal Activity, and 3D‐QSAR of Novel 1,3,4‐Oxadiazole/ Thiadiazole Thioether Derivatives

AbstractForty one novel 1,3,4‐oxadiazole/thiadiazole thioether derivatives containing phenoxy moiety were designed and synthesized. Bioassay demonstrated that some of them showed remarkable activities against Tylenchulus semipenetrans in vitro and in vivo. Compounds 20, 21, 35 and 39 showed excellent lethal activities after treatment for 48 h in vitro, with LC50 values of 13.4 ± 1.8, 11.7 ± 2.5, 13.7 ± 2.4 and 13.3 ± 1.1 mg·L–1, respectively, which were obviously superior to fosthiazate (49.1 ± 2.8 mg·L–1) and avermectin (26.6 ± 2.3 mg·L–1). Compound 21 can effectively control the citrus nematode disease caused by T. semipenetrans at 200 mg·L–1 in vivo with (68 ± 3)% inhibitory effect, which was even better than that of avermectin ((63 ± 2)%). The CoMFA and CoMSIA models of three‐dimensional quantitative structure‐activity relationships (3D‐QSARs) were established. The compound 33 was designed based on the 3D‐QSAR models with more vigorous nematicidal activities in vitro (LC50 = 9.8 ± 1.4 mg·L–1) and in vivo ((70 ± 5)%). These results demonstrated that compound 33 can be considered as a potential nematicide.