Synthesis and evaluation of antiparasitic activities of new 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine derivatives

A series of new 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine derivatives, prepared by two synthetic routes, were in vitro assayed against three Trypanosoma strains, Leishmania donovani, and Plasmodium falciparum K1. Seven out of 17 compounds showed moderate to very good activity against blood stage T. b. rhodesiense, with 10 and 17 exhibiting highest potency (IC50 of 1.0 and 1.1 microM, respectively). Interestingly, the beta-diketone precursors 1-3 had good antitrypanosomal activity toward the insect stage, with IC50 values of 1.0-3.4 microM. Among different compounds with moderate activity against T. cruzi, compound 17 showed the lowest IC50 value of 9.5 microM; thus, the series seemed to act selectively toward the different Trypanosoma parasites. Eight compounds were moderately active against L. donovani, with 2, 3, and 12 being the most promising ones (IC50 values of 2.3-5.2 microM), whereas compound 14 was the only derivative with good activity against P. falciparum (IC50 of 3.7 microM).     

Synthesis and anticonvulsant activity of 4-(2-phenoxyphenyl)semicarbazones

A new series of 4-(2-phenoxyphenyl)semicarbazones were synthesized as potential anticonvulsant agents. Thus, the reaction of 4-(2-phenoxyphenyl)semicarbazide with various benzaldehydes and acetophenones in ethanol yielded the corresponding semicarbazones 6a–k and 7a–i, respectively. Structures of the synthesized compounds were confirmed by spectral data and elemental analysis. All compounds were evaluated for their anticonvulsant activity in pentylenetetrazole (PTZ)-induced kindling model in adult male Wistar rats. The neurotoxicity of active compounds was also assessed using the rotorod method. The results showed that two compounds (6g and 6i) showed greater protection from seizure than sodium valproate at dose of 100 mg/kg. Compounds 6g and 6i showed no neurotoxicity at the maximum dose administered (300 mg/kg).     

Synthesis, analgesic and anti-inflammatory activity of 4-(2-phenoxyphenyl)semicarbazones

A series of 4-(2-phenoxyphenyl)semicarbazones was synthesized and evaluated for their analgesic and anti-inflammatory activities. Several compounds (e. g. 10h, 10i, and 11i) were found to be more potent than the reference drug mefenamic acid in the formalin test. Based on the results of an anti-inflammatory study, 1-(1-(2,5-dimethoxyphenyl)ethylidene)-4-(2-phenoxyphenyl)semicarbazide 11i was the most active compound.     

Synthesis and evaluation of antibacterial and antifungal activities of new (Z)-3-bromo-4-(1,3-diaryl-1H-pyrazol-4-yl)but-3-en-2-ones and 4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-1,3-diaryl-1H-pyrazoles

Bromination of 4-(1, 3-diaryl-1H-pyrazol-4-yl) but-3-en-2-ones, triggered by a combination of potassium bromide and cerium(IV) ammonium nitrate in a biphasic system consisting of water and dichloromethane furnishes the corresponding monobromo compounds 2 directly, instead of the expected dibromo compounds. The α-bromo compounds 2 were utilized as efficient precursors for the synthesis of several bipyrazolyl derivatives, 4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-1, 3-diaryl-1H-pyrazoles (3). All the α-bromoenones 2 and bipyrazoles 3 are new compounds and their identity was established by m.p., spectral and analytical data. The new products 2 and 3 were tested for their in vitro antibacterial activity against Staphylococcus aureus, Bacillus subtilis (Gram positive), Escherichia coli, and Pseudomonas aeruginosa (Gram negative) and antifungal activity against Aspergilus flavus and Aspergillus niger. The antimicrobial activity of the tested compounds is compared with the commercially available antibiotic, ciprofloxacin and antifungal agent, fluconazole.     

Synthesis, antibacterial, and antifungal activities of biolabile (E)-1-(4-morpholinophenyl)-3-aryl-prop-2-en-1-ones

Abstract  A collection of biolabile (E)-1-(4-morpholinophenyl)-3-aryl-prop-2-en-1-ones 8–13 are synthesized, characterized by melting point, elemental analysis, mass spectroscopy (MS), Fourier-transform infrared (FT-IR), and ¹H and ¹³C nuclear magnetic resonance (NMR) spectroscopic data and evaluated for their in vitro antibacterial and antifungal activities. Compounds 8–13 exerted a wide range of antibacterial activities against all tested Gram-positive and Gram-negative bacterial strains. All the compounds 8–13 were more active against Pseudomonas. Of the synthesized compounds, compounds 9 and 11 exhibited a wide range of antibacterial activities against Staphylococcus aureus, β-Heamolytic streptococcus, Escherichia coli, Klebsiella pneumonia, and Pseudomonas. Compounds 10, 12, and 13 exerted strong antifungal activities against all tested fungal strains, namely Aspergillus flavus, Mucor, Rhizopus, and Microsporum gypsuem. Graphical Abstract        

Synthesis and antimicrobial activities of some new 5-((3-(aryl)-1-phenyl-1H-pyrazol-4-yl)methylene)-3-phenylthiazolidine-2,4-diones

A series of nine new compounds of 5-((3-(aryl)-1-phenyl-1H-pyrazol-4-yl)methylene)-3-phenylthiazolidine-2,4-diones was synthesized by Knoevenagel condensation of various 3-(aryl)-1-phenyl-1H-pyrazole-4-carbaldehydes with 3-phenylthiazolidine-2,4-dione in ethanol in the presence of piperidine as a catalyst. The reaction afforded the desired products in good yields. All the nine compounds were screened for their in vitro antibacterial (Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli) and antifungal (Aspergillus niger and A. flavus) activity. Biological activities of these compounds were compared with those of commercially available antibiotics, ciprofloxacin and antifungal agent fluconazole. Two compounds 3e and 3i were found to be most effective against S. aureus and B. subtilis. Out of the nine compounds tested for antifungal activity, five, 3c–f and 3h showed more than 50% inhibition against the A. flavus, whereas the three compounds 3a, 3d and 3f showed more than 50% inhibition against A. niger.     

Syntheses and antifungal activities of 1-[4-phenyl-2-(phenylthio or acyloxy)-n-butyl]-1H-imidazole derivatives]

The title compounds (4b, d-f, h-j) were prepared from 1-[4-(p-substituted phenyl)-2-chloro-n-butyl]-1H-imidazoles and the corresponding thiophenols or mercaptopyridines. Acyloxy compounds (5a-e) were prepared from alcohol (2b) and the corresponding acyl chlorides. In the antifungal activity test, p-tolyl compounds (4e, f) showed as good activity as butoconazole (4c).     

Synthesis and antifungal activity of new N-(1-phenyl-4-carbetoxypyrazol-5-yl)-, N-(indazol-3-yl)- and N-(indazol-5-yl)-2-iodobenzamides

N-(1-Phenyl-4-carbetoxypyrazol-5-yl)-, N-(indazol-3-yl)- and N-(indazol-5-yl)-2-iodobenzamides 6, with a Benodanil-like structure, were synthesized by refluxing in acetic acid the corresponding benzotriazinones 5 with potassium iodide for 1 h in order to study the role on the antifungal activity of the N-substitution with an aromatic heterocyclic system on benzamide moiety. Among the tested iododerivatives, compounds 6d,f,g,h possess interesting activities toward some phytopathogenic fungal strains.     

3-(4-phenoxyphenyl)pyrazoles: a novel class of sodium channel blockers

A series of 3-(4-phenoxyphenyl)-1H-pyrazoles were synthesized and characterized as potent state-dependent sodium channel blockers. A limited SAR study was carried out to delineate the chemical requirements for potency. The results indicate that the distal phenyl group is critical for activity but will tolerate lipophilic (+pi) electronegative (+sigma) substituents at the ortho and/or para position. Substitution at the pyrazole nitrogen with a H-bond donor improves potency. Compound 18 showed robust activity in the rat Chung neuropathy paradigm.     

Synthesis of 3-[2-(2,3-dihydro-5-phenyl-4-substituted-3H-1,2,4- triazole-3-thione-2-yl)-acetylamino]-2-methyl-4(3H)-quinazolinones and their pharmacological activities

Some 2-methyl-3-triazole-substituted-4(3H)-quinazolinones 3a-f were prepared and tested for their H1- and H2-antihistaminic activities. In addition these compounds are central nervous system depressants and anticonvulsants. 3e shows highly significant decrease of locomotor activity.     

含氧叔丁基三唑醇类化合物的合成及其体外抗真菌活性

目的设计合成含氧取代的叔丁基三唑醇类化合物并研究其体外抗真菌活性。方法以一氯频那酮为起始原料经多步反应合成目标化合物,化合物结构经1H-NMR谱、IR谱确证;选择8种真菌为实验菌株,按国际标准抗真菌敏感性实验方法测定体外抑菌活性。结果与结论合成了12个新化合物。所有目标化合物对8种真菌均具有一定的抑制作用。可以将现有的三唑醇类抗真菌药物结构中的2,4-二氟苯基替换成其他疏水性基团来设计抗真菌化合物。     

Synthesis of (1E)-phenyl-2-(3',4'-dihydroxyphenyl)ethenesulfonates as potent neuroprotective agents and evaluation of their activities

A series of (1E)-phenyl-2-(3',4'-dihydroxyphenyl)ethenesulfonate derivatives were designed and synthesized as anti-amyotrophic lateral sclerosis (ALS) agents, based on the lead compound caffeic acid phenethyl ester (CAPE). And their neuroprotective activities were evaluated. The results indicated that replacement of the carboxylic ester by sulfonic ester did not produce better neuroprotective activity in the model of LPS induced inflammation in BV2 cells. However, the results in the model of H2O2 induced damage in PC12 cells showed that the neuroprotective activities of all the target compounds and CAPE were about the same.     

Synthesis and Antimicrobial Activity of Some New 2-(3-(4-Aryl)-1-phenyl-1H-pyrazol-4-yl) Chroman-4-ones

Seven new 2-(3-(4-aryl)-1-phenyl-1H-pyrazol-4-yl) chroman-4-ones (4a-4g) have been synthesized by cyclization of 2-hydroxychalcone analogues of pyrazole 3a-3g using conc. HCl in acetic acid. The structures of the compounds 4a-4g were established by the combined use of (1)HNMR, IR and mass spectra. All the seven compounds were tested in vitro for their antibacterial activity against two Gram positive bacteria namely Staphylococcus aureus and Bacillus subtilis and two Gram negative bacteria Escherichia coli and Pseudomonas aeruginosa. The compounds 4b, 4c, 4e, 4f, 4g have displayed good antibacterial activity when compared with commercially available antibiotic, ciprofloxacin. These compounds also were screened for their antifungal activity against two ear pathogenic fungi, namely Aspergillus Niger and A. flavus. The compounds 4a, 4c, 4d, 4g exhibited good antifungal activity when compared with commercially available antifungal, fluconazole.     

Synthesis and antileukemic activity of new 3-(1-phenyl-3-methylpyrazol-5-yl)-2-styrylquinazolin-4(3H)-ones

3-(1-Phenyl-3-methylpyrazol-5-yl)-2-styrylquinazolin-4(3H)-ones 14a-q and 15a-q were synthesized by refluxing in acetic acid the corresponding 2-methylquinazolinones 12 and 13 with the opportune benzoic aldehyde for 12 h. The synthesized styrylquinazolinones 14a-q and 15a-q were tested in vitro for their antileukemic activity against L1210 (murine leukemia), K562 (human chronic myelogenous leukemia) and HL60 (human leukemia) cell lines showing in some cases good activity.     

4-(甲基苯胺基)-3-氰基喹啉类衍生物的 合成及抗肿瘤活性

目的 设计合成4-(甲基苯胺基)-3-氰基喹啉类衍生物,并对其体外抗肿瘤活性进行初步评价。 方法 以氰乙酸乙酯为起始原料,经多步反应合成目标化合物。采用MTT法,以吉非替尼（gefitinib）为阳性对照药,以A549、HT-29和MDA-MB-231为测试细胞株对目标化合物的抗肿瘤活性进行了评价。 结果 合成了18个新化合物,经1H-NMR、MS和IR确认其结构。体外活性测试结果显示,多数化合物可在较低浓度抑制肿瘤细胞增殖,其中的Ⅶ2、Ⅶ3、Ⅶ6、Ⅶ12、Ⅶ13、Ⅶ15 和 Ⅶ16共7个化合物有显著的抗增殖活性,优于阳性对照药吉非替尼。 结论 体外活性实验表明：4-(甲基苯胺基)-3-氰基喹啉类衍生物作为新型的酪氨酸激酶抑制剂,其构效关系值得进一步研究。     

含哌嗪环的三唑醇类化合物的合成及体外抗真菌活性

目的设计合成含哌嗪环侧链的三唑醇类化合物并研究其体外抗真菌活性。方法以2-氯-2′,4′-二氟苯乙酮为起始原料经多步反应合成目标化合物，化合物结构经IR、^1H-NMR谱确证；选择8种真菌为实验菌株，按国际标准抗真菌敏感性实验方法测定体外抑菌活性。结果设计合成了11个新化合物。所有目标化合物对8种真菌均具有一定的抑制作用。结论多个目标化合物的抗真菌活性明显高于阳性对照药氟康唑，其中化合物11具有广谱、高活性的优点，其体外抗真菌活性与对照药伊曲康唑相当，有进一步研究开发的价值。     

Synthesis of 3-(4-substituted benzoylmethyl)-2-benzoxazolinones and screening antimicrobial activities

A number of 3-(4-substituted benzoylmethyl)-2-benzoxazolinones have been synthesized by reacting with 2-benzoxazolinone and 4-substituted phenacyl bromide in ethanol. Their chemical structures were confirmed by IR, 1H NMR and elemental analysis. For screening antimicrobial activity, minimum inhibitory concentration (MIC) values were determined against two Gram positive, one Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus) and three yeast-like the fungi (Candida albicans, Candida krusei, Candida parapsilosis).