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Upstream product

• 589-18-4 4-Methylbenzyl alcohol 
• 403-41-8 1-(4-Fluorophenyl)ethanol 
• 104-87-0 4-methyl-benzaldehyde 
• 403-42-9 1-(4-fluorophenyl)ethanone 

Downstream Products

• 870680-35-6 3-(4-fluoro-phenyl)-5-p-tolyl-4,5-dihydro-pyrazole-1-carbothioic acid amide 
• 1448042-20-3 3-(4-fluoro-phenyl)-1-p-tolyl-hexa-1,5-dien-3-ol 
• 1366267-78-8 2-(3-(4-fluorophenyl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one 
• 84857-18-1 4-(4-Fluoro-phenyl)-6-p-tolyl-pyrimidin-2-ylamine 
• 313236-76-9 C₂₂H₂₀FN₃O₂S 
• 1430116-69-0 C₂₂H₂₀FN₃O₂S 

Relevant academic research and scientific papers

Pharmacophore hybridization approach to discover novel pyrazoline-based hydantoin analogs with anti-tumor efficacy

In search for new and safer anti-cancer agents, a structurally guided pharmacophore hybridization strategy of two privileged scaffolds, namely diaryl pyrazolines and imidazolidine-2,4-dione (hydantoin), was adopted resulting in a newfangled series of compounds (H1-H22). Herein, a bio-isosteric replacement of “pyrrolidine-2,5-dione” moiety of our recently reported antitumor hybrid incorporating diaryl pyrazoline and pyrrolidine-2,5-dione scaffolds with “imidazoline-2,4-dione” moiety has been incorporated. Complete biological studies revealed the most potent analog among all i.e. compound H13, which was at-least 10-fold more potent compared to the corresponding pyrrolidine-2,5-dione, in colon and breast cancer cells. In-vitro studies showed activation of caspases, arrest of G0/G1 phase of cell cycle, decrease in the expression of anti-apoptotic protein (Bcl-2) and increased DNA damage. In-vivo assay on HT-29 (human colorectal adenocarcinoma) animal xenograft model unveiled the significant anti-tumor efficacy along with oral bioavailability with maximum TGI 36% (i.p.) and 44% (per os) at 50 mg/kg dose. These findings confirm the suitability of hybridized pyrazoline and imidazolidine-2,4-dione analog H13 for its anti-cancer potential and starting-point for the development of more efficacious analogs.

Design, synthesis, and SAR study of novel 4,5-dihydropyrazole-Thiazole derivatives with anti-inflammatory activities for the treatment of sepsis

Systemic inflammatory response syndrome is a major feature of sepsis which is one of the major causes of death worldwide. It has been reported that 3,5-diaryl-4,5-dihydropyrazole and thiazole derivatives have many biological functions, especially in the aspect of anti-inflammation. According to the strategy of pharmacophore combination, we introduced thiazole moiety into dihydropyrazole skeleton to design and synthesize a novel series of 2-(3,5-diphenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-methylthiazole derivatives, and evaluated their anti-inflammatory activities for sepsis treatment. Preliminary structure?activity relationship (SAR) analysis was conducted by their inhibitory activities against nitric oxide (NO) release in LPS-induced RAW264.7 cells, and the optimal compound E26 exhibited more potent anti-inflammatory activity than the positive control treatment indomethacin and dexamethasone. In further mechanism study, our results showed that compound E26 significantly suppressed the production of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), NO and inhibited the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) through blocking MAPKs signaling pathway. In addition, in vivo administration of compound E26 resulted in a significant improvement of LPS-induced sepsis in C57BL/6J mice, with reducing toxicity in multiple organs. Taken together, this study demonstrated the compound E26 could be a promising agent for the treatment of sepsis.

Multi-target weapons: diaryl-pyrazoline thiazolidinediones simultaneously targeting VEGFR-2 and HDAC cancer hallmarks

In anticancer drug discovery, multi-targeting compounds have been beneficial due to their advantages over single-targeting compounds. For instance, VEGFR-2 has a crucial role in angiogenesis and cancer management, whereas HDACs are well-known regulators o

Double-edged Swords: Diaryl pyrazoline thiazolidinediones synchronously targeting cancer epigenetics and angiogenesis

In the present study, two novel series of compounds incorporating naphthyl and pyridyl linker were synthesized and biological assays revealed 5-((6-(2-(5-(2-chlorophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-oxoethoxy) naphthalene-2-yl)methylene)thiazolidine-2,4-dione (14b) as the most potent dual inhibitors of vascular endothelial growth factors receptor-2 (VEGFR-2) and histone deacetylase 4 (HDAC4). Compounds 13b, 14b, 17f, and 21f were found to stabilize HDAC4; where, pyridyl linker swords were endowed with higher stabilization effects than naphthyl linker. Also, 13b and 14b showed best inhibitory activity on VEGFR-2 as compared to others. Compound 14b was most potent as evident by in-vitro and in-vivo biological assessments. It displayed anti-angiogenic potential by inhibiting endothelial cell proliferation, migration, tube formation and also suppressed new capillary formation in the growing chick chorioallantoic membranes (CAMs). It showed selectivity and potency towards HDAC4 as compared to other HDAC isoforms. Compound 14b (25 mg/kg, i.p.) also indicated exceptional antitumor efficacy on in-vivo animal xenograft model of human colorectal adenocarcinoma (HT-29). The mechanism of action of 14b was also confirmed by western blot.

Synthesis and Biological Evaluation of Pyrazoline and Pyrrolidine-2,5-dione Hybrids as Potential Antitumor Agents

In search of novel and effective antitumor agents, pyrazoline-substituted pyrrolidine-2,5-dione hybrids were designed, synthesized and evaluated in silico, in vitro and in vivo for anticancer efficacy. All the compounds exhibited remarkable cytotoxic effects in MCF7 and HT29 cells. The excellent antiproliferative activity toward MCF7 (IC50=0.78±0.01 μM), HT29 (IC50=0.92±0.15 μM) and K562 (IC50=47.25±1.24 μM) cell lines, prompted us to further investigate the antitumor effects of the best compound S2 (1-(2-(3-(4-fluorophenyl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-oxoethyl)pyrrolidine-2,5-dione). In cell-cycle analysis, S2 was found to disrupt the growth phases with increased cell population in G1/G0 phase and decreased cell population in G2/M phase. The excellent in vitro effects were also supported by inhibition of anti-apoptotic protein Bcl-2. In vivo tumor regression studies of S2 in HT29 xenograft nude mice, exhibited equivalent and promising tumor regression with maximum TGI, 66 % (i. p. route) and 60 % (oral route) at 50 mg kg?1 dose by both the routes, indicating oral bioavailability and antitumor efficacy. These findings advocate that hybridization of pyrazoline and pyrrolidine-2,5-dioes holds promise for the development of more potent and less toxic anticancer agents.

Synthesis of sulfonamides bearing 1,3,5-triarylpyrazoline and 4-thiazolidinone moieties as novel antimicrobial agents

Two series of sulfonamides were synthesized from 4-hydrazinylben-zenesulfonamide as the key starting material. 1,3,5-Triarylpyrazoline sulfonamides (2a-i) were obtained by cyclocondensation of various chalcones in 53-64 % yields, while 4-thiazolidinone derivatives (4a-e) were synthesized by cyclocondensation between mercaptoacetic acid and different phenylhydrazones in 43-62 % yields. The synthesized compounds were characterized based on FTIR, 1H-NMR, 13C-NMR and HRMS data. The sulfonamides were evaluated for their in vitro antimicrobial activities against four bacterial strains (E. coli, P. aeruginosa, B. subtillis and S aureus), two filamentous fungal strains (A. Niger and F. oxysporum) and two yeast strains (C. albicans and S. cerevisiae). Seven pyrazolines, 2a-c and 2e-h, exhibited significant inhibition of different microbial strains. Among them, compound 2b displayed good antifungal activity against A. Niger (MIC value at 12.5 μg mL-1) over the reference drug.

Synthesis and theoretical study of a series of 3,5-disubstitutes pyrazoles

In this work, we proposed the synthesis of a series of pyrazoles derivatives with different substituents on the aromatic rings. We aim to evaluate their influence on the reactivity of the compounds in reactions of α,β-unsaturated chalcones and sulfonyl hydrazide catalyzed by iodine. In order to explain their high and low yields, or the impossibility of obtaining some compounds by applied synthetic methodology, Density Functional Theory (DFT) calculations were performed. The reaction Gibbs free energy (ΔG) as well as the energy gap of the HOMO-LUMO frontier orbitals (ΔE) of some selected reactants could explain qualitatively the experimental observations in terms of synthesis yield. In this way, we believe that the chemical nature of aromatic ring substituents is relevant for the reactivity of the starting materials as well as the formation of the desired products.

Synthesis and biological evaluation of coumarin clubbed thiazines scaffolds as antimicrobial and antioxidant

A new series of 4-methyl-6-nitro-2-oxo-2H-chroman-7yl-2-(4-(4-fluorophenyl)-6-phenyl-2H-1,3-thiazin-2-yl-amino)acetates 5a–j were synthesized from 6-nitro-4-methyl coumarinyl chloroacetate (5) and 2-amino thiazines (IIIa–j). The structure of the final compounds was adequately confirmed via spectroscopic techniques (IR, 1H NMR, 13C NMR, Mass) and characterization of physical properties. Final compounds were screened for their antimicrobial, antitubercular, and antioxidant activities. Compounds 5c and 5h found to have antibacterial potency against E. coli with MIC values 50 μg/mL compared to standard drugs. Compound 5d demonstrated better antifungal potency (MIC = 200 μg/mL) against C. albicans when compared with griseofulvin. Compounds 5b and 5h found to be encouraging antitubercular (MIC = 62.5 μg/mL with 98–99% inhibition) against M. tuberculosis H37Rv. The newly synthesized 5h and 5b were appeared to have high radical scavenging efficacies as 33.99 ± 0.301 and 35.35 ± 0.470 μg/mL ± SD of IC50 values, respectively, in DPPH and ABTS bioassay.

Synthesis, spectroscopic and computational characterization of the tautomerism of pyrazoline derivatives from chalcones

In the present study a series of novel pyrazolines derivatives has been synthesized, and their structures assigned on the basis of FT-Raman, 1H and 13C NMR spectral data and computational DFT calculations. A joint computational study using B3LYP/6-311G(2d,2p) density functional theory and FT-Raman investigation on the tautomerism of 3-(4-substituted-phenyl)-4,5-dihydro-5-(4-substituted-phenyl)pyrazole-1-carbothioamide and 3-(4-substituted-phenyl)-4,5-dihydro-5-(4-substituted-phenyl)pyrazole-1-carboxamide are presented. The structures were characterized as a minimum in the potential energy surface using DFT. The calculated Raman and NMR spectra were of such remarkable agreement to the experimental results that the equilibrium between tautomeric forms has been discussed in detail. Our study suggests the existence of tautomers, the carboxamide/carbothioamide group may tautomerize, in the solid state or in solution. Thermodynamic data calculated suggests that the R(CS)NH2 and R(CO)NH2 species are more stable than the R(CNH)SH and R(CNH)OH species. Additionally, results found for the 1H NMR shifting, pointed out to which structure is present.

Co-N-C Catalyst for C-C Coupling Reactions: On the Catalytic Performance and Active Sites

C-C bond-forming reactions are important in chemistry for construction of complex large molecules from readily available simple substrates. However, they usually involve the employment of organic halides and suffer from toxic or environmental issues. We report an efficient and environmentally benign methodology-aerobic oxidative cross-coupling of primary and secondary alcohols-to directly produce α,β-unsaturated ketones that are key intermediates for synthesis of agrochemical, pharmaceutical, and other fine chemicals. A noble-metal-free Co-N-C catalyst, derived from pyrolysis of cobalt-phenanthroline complexes on a mesoporous carbon support, is developed toward the target reactions and shows high catalytic activity (turnover frequency of 3.8 s-1 based on Co single atoms, surpassing the state of art in the literature), good recyclability, and wide applicability to diverse substrates (28 examples). The active sites in the Co-N-C catalyst are proposed to be Co single atoms bonded with N within graphitic sheets.