Pyrazole Carboxamide Derivatives Research Articles

Design, Synthesis, DFT Study and Antifungal Activity of Pyrazolecarboxamide Derivatives.

A series of novel pyrazole amide derivatives were designed and synthesized by multi-step reactions from phenylhydrazine and ethyl 3-oxobutanoate as starting materials, and their structures were characterized by NMR, MS and elemental analysis. The antifungal activity of the title compounds was determined. The results indicated that some of title compounds exhibited moderate antifungal activity. Furthermore, DFT calculations were used to study the structure-activity relationships (SAR).

Synthesis and Bioactivities of Novel 1‐(3‐Chloropyridin‐2‐yl)‐N‐Substituted‐5‐(Trifluoromethyl)‐Pyrazole Carboxamide Derivatives

A series of novel 1‐(3‐chloropyridin‐2‐yl)‐N‐substituted‐5‐(trifluoromethyl)‐pyrazole carboxamide derivatives TC1, TC2, TC3, TC4, TC5, TC6, TC7, TC8, TC9, TC10, TC11 were synthesized and characterized by IR, 1H NMR, 13C NMR, MS, and elemental analysis. All the target compounds were tested in vitro for their antibacterial activities and antifungal activities. The preliminary bioassays indicated that compound TC6 exhibited excellent activity against Xanthomonas oryzae (94.9% and 84.9%) at different concentrations (200 µg/mL and 100 µg/mL), which was higher than that of Bismerthiazol (94.6% and 64.0%), respectively. At the same time, most of the compounds exhibited moderate antifungal activities against four kinds of phytopathogenic fungi

Synthesis and antifungal activity of the derivatives of novel pyrazole carboxamide and isoxazolol pyrazole carboxylate.

A series of pyrazole carboxamide and isoxazolol pyrazole carboxylate derivatives were designed and synthesized in this study. The structures of the compounds were elucidated based on spectral data (infrared, proton nuclear magnetic resonance and mass spectroscopy). Then, all of the compounds were bioassayed in vitro against four types of phytopathogenic fungi (Alternaria porri, Marssonina coronaria, Cercospora petroselini and Rhizoctonia solani) using the mycelium growth inhibition method. The results showed that some of the synthesized pyrazole carboxamides displayed notable antifungal activity. The isoxazole pyrazole carboxylate 7ai exhibited significant antifungal activity against R. solani, with an EC50 value of 0.37 μg/mL. Nonetheless, this value was lower than that of the commercial fungicide, carbendazol.

New 1-phenyl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides inhibit hepatitis C virus replication via suppression of cyclooxygenase-2.

We report here the synthesis and mechanism of inhibition of pyrazolecarboxamide derivatives as a new class of HCV inhibitors. Compounds 6, 7, 8 and 16 inhibited the subgenomic HCV replicon 1b genotype at EC50 values between 5 and 8 μM and displayed an even higher potency against the infectious Jc1 HCV 2a genotype. Compound 6 exhibited an EC50 of 6.7 μM and selectivity index of 23 against HCV 1b, and reduced the RNA copies of the infectious Jc1 chimeric 2a clone by 82% at 7 μM. Evaluation of the mode of anti-HCV activity of 6 revealed that it suppressed HCV-induced COX-2 mRNA and protein expression, displaying an IC50 of 3.2 μM in COX-2 promoter-linked luciferase reporter assay. Conversely, the anti-HCV activity of 6 was abrogated upon over-expression of COX-2. These findings suggest that 6 as a representative of these pyrazolecarboxamides function as anti-HCV agents via targeting COX-2 at both the transcription and translation levels.

ChemInform Abstract: Synthesis and X‐Ray Structure Characterization of Novel Pyrazole Carboxamide Derivatives

Abstractcontaining a piperazine moiety

Synthesis and X-ray Structure Characterisation of Novel Pyrazole Carboxamide Derivatives

A series of novel pyrazole carboxamide derivatives containing piperazine moiety was synthesised and determined by IR, 1H NMR and HRMS spectroscopy. Especially, the structure was confirmed by the X-ray crystal analysis of [1-(4- tert-butylbenzyl)-4-chloro-3-(4-chlorophenyl)-1 H-pyrazol-5-yl](4-phenylpiperazin-1-yl)methanone.

Synthesis and Discovery of Novel Pyrazole Carboxamide Derivatives as Potential Osteogenesis Inducers

A series of novel N-aryl-3-aryl-1-arylmethyl-1H-pyrazole-5-carboxamide derivatives 4a-l was synthesized by the reaction of 3-aryl-1-arylmethyl-1H-pyrazole-5-carbonyl chloride with substituted aniline in good to excellent yields. Structures of the compounds were determined by IR, (1) H NMR, and HR-MS spectroscopy. The molecular structure was confirmed by the X-ray crystal analysis of one compound (4j) that was prone to crystallization. These compounds were used to induce mouse osteoblast precursors MC3T3-E1 into osteoblasts and the induction was assessed by alkaline phosphatase (ALP) activity and the gene expression of bone sialoprotein (BSP). The results showed that the compounds 4a-d, 4g, 4h, and 4k could increase the ALP activity in comparison with the negative control group and compound 4h was the most effective one which could induce osteogenesis. Furthermore, mRNA expression of BSP which is a marker of osteogenesis was up-regulated by the compound 4h.

Synthesis and antifungal activity of novel pyrazolecarboxamide derivatives containing a hydrazone moiety

BackgroundThe plant pathogenic fungus (such as Gibberella zeae, Fusarium oxysporum and Cytospora mandshurica) causes devastating disease in agriculture. The pathogenic fungus is responsible for billions of dollars in economic losses worldwide each year. In order to discover new fungicidal molecule with good fungicidal activity against G. zeae, F. oxysporum, and C. mandshurica, we sought to combine the active sub-structure of hydrazone and pyrazole amide derivatives together to design and synthesize novel pyrazole amide derivatives containing a hydrazone moiety.ResultsA series of novel pyrazole amide derivatives bearing hydrazone moiety were synthesized. Their structures were characterized by 1 H-NMR, 13 C-NMR, IR, and elemental analysis. The preliminary biological assays revealed that most of the synthesized compounds exhibit favorable antifungal activities against G. zeae. The activity of compounds 7a, 7f, 7g, 7h, 7i, 7j, 7l and 7q were 40.82%, 47.78%, 50.32%, 40.82%, 49.05%, 48.73%, 40.19% and 45.89%, respectively, and the synthesized compounds showed certain antifungal activities against F. oxysporum and C.mandshurica.ConclusionA practical synthetic route to pyrazole amide derivatives containing a hydrazone moiety were synthesized by the condensation of intermediates 5-chloro-N-(4-subsititued-2-(hydrazinecarbonyl)-6-methylphenyl)-1,3-dimethyl-1 H-pyrazole-4-carboxamide with different aldehydes or ketones in ethanol at room temperature is presented, the results of the study suggested that the pyrazole amide derivatives containing hydrazone moieties could inhibit the growth of G. zeae, F. oxysporium and C. mandshurica to a certain extent.

Inhibitory effect of novel pyrazole carboxamide derivatives on human carbonic anhydrase enzyme

The synthesis, characterization and biological evaluation of novel pyrazole carboxamide derivatives (2–9) are presented. 1H and 13C NMR have been used for the structure description, possible tautomeric structures determination and hydrogen bonding observation. FT-IR results have confirmed the synthesis of the pyrazole derivatives while thermal gravimetric analysis has confirmed thermal stability up to 300°C. The melting temperatures are strongly dependent on their crystal structure as confirmed by differential scanning calorimetry and X-ray diffraction measurements. Impacts of 2–9 as possible antiglaucoma agents were investigated on carbonic anhydrase I and II (CA-I and II) isozymes purified from human erythrocytes in vitro. Compounds 3 and 9 had the highest inhibitory effect while compounds 6 and 8 showed the lowest inhibition.

Synthesis of novel pyrazole carboxamide derivatives and discovery of modulators for apoptosis or autophagy in A549 lung cancer cells

A series of novel 3-aryl-1-arylmethyl-1 H-pyrazole-5-carboxamide derivatives 3a– l, were synthesized by the reaction of 3-aryl-1-arylmethyl-1 H-pyrazole-5-carbonyl chloride with substituted amine in excellent yields. The compounds 3e– h could suppress A549 lung cancer cell growth. More interestingly, compounds 3e and 3f might inhibit the A549 cell growth by inducing apoptosis; whereas compounds 3g and 3h with fluorine group might inhibit the A549 cell growth by inducing autophagy.

Hair growth stimulator property of thienyl substituted pyrazole carboxamide derivatives as a cb1 receptor antagonist with in vivo antiobesity effect

A few thienyl substituted pyrazole derivatives were synthesized to aid in the characterization of the cannabinoid receptor antagonist and also to serve as potentially useful antiobesity agent. Structural requirements for selective CB1 receptor antagonistic activity of 5-thienyl pyrazole derivatives included the structural similarity with potent, specific antagonist rimonabant 1. Compound 3 has been identified as a hair growth stimulator and an antiobesity agent in animal models.

Synthesis and Selective Bioactivity of New Pyrazolecarboxamide Derivatives

ピラゾール環を骨格とする新しい系統の化合物を合成し, その殺ダニ活性と魚毒性を調べた. N-フェノキシエチルピラゾール-5-カルボキサミド誘導体 (III) に, ナミハダニに対する高い活性が認められた. しかしながら, メダカに対する毒性も高いレベルにあった. そこでN-フェノキシエチルピラゾール-5-カルボキサミド誘導体 (III) を基にして, ハダニと魚間の活性選択性を得るために, N-アシル-N-フェノキシエチルピラゾール-5-カルボキサミド誘導体 (IV) へと導いた. 生物試験の結果, N-アシル化誘導体 (IV) のいくつかの化合物に, 高い殺ダニ活性を維持しながら, 魚毒性の低い化合物を見出した. この選択活性は, N-アシル化誘導体 (IV) のなかでピラゾール環の4位が無置換で, 3位に tert-ブチル基が導入された時, 最も大きかった.

Synthesis and Acaricidal Activity of <i>N</i>-(3-Pyridylmethyl)pyrazolecarboxamide Derivatives

Synthesis and Acaricidal Activity of <i>N</i>-(3-Pyridylmethyl)pyrazolecarboxamide Derivatives