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N-Heterocycles
Published in Navjeet Kaur, Metals and Non-Metals, 2020
Pyrazolones are used in drugs and are of pharmacological importance, for they exhibit a number of medically useful properties—anti-fungal, anti-microbial, anti-bacterial, anti-mycobacterial, anti-tumor, anti-platelet, anti-inflammatory, anti-depressant, gastric secretion stimulatory as well as anti-filarial. They also work as substrates for pigments, dyes, chelating agents and pesticides [1–3]. Moreover, pyrazolones act as inhibitors against CDK2, with remarkable activity against a number of human tumor cell lines, cannabinoid type-1 (CB1) receptor antagonists, and against tissue-nonspecific alkaline phosphatase (TNAP). In pesticide chemistry, they have come to be used as fungicides, insecticides and herbicides. Pyrazole moiety is a core structure of a wide range of biologically active compounds such as blockbuster drugs like celecoxib and sildenafil (viagra). Whereas celecoxib exhibits anti-arthritic and analgesic activities and is a powerful COX-2 inhibitor, sildenafil (viagra) is a FDA approved drug used to treat erectile dysfunction [4–5].
Microwave-Assisted Transition Metal-Catalyzed Synthesis of Pharmaceutically Important Heterocycles
Published in Banik Bimal Krishna, Bandyopadhyay Debasish, Advances in Microwave Chemistry, 2018
Dipti Shukla, Priyank Purohit, Asit K. Chakraborti
The fused pyrazole derivatives have been recognized as biologically important scaffold, and among them, the pyrazolo[3,4-b]pyridine, pyrazolo[3,4-b]quinoline, pyrazolo[1,5-a]pyrimidine, and pyrazolo[1,5-a]quinazoline moieties are an integral part of marketed drugs. The pyrazolo[3,4-b]pyridine derivatives 33 were synthesized through Pd-catalyzed microwave-assisted reaction of β-bromovinyl/aryl aldehyde 31 with 5-aminopyrazoles/3-amino pyrazole derivatives 32 and 32a under solvent-free conditions [52]. The use of 2.5 mol% of Pd(OAc)2 in neat condition under microwave (700 W) for 15 min was the optimal condition to provide the fused pyrazolo[3,4-b]pyridine 33 in good to excellent yields. The imine side product, which was formed in conventional heating conditions was not present under microwave heating conditions. The optimized reaction condition was used to investigate the scope of 3-aminopyrazole derivatives 32a to form various substituted pyrazolo[1,5-a]pyrimidines 34 (Scheme 9.14). All synthesized compounds were screened for in vitro activities against cervical HeLa cancer cell line and prostate DU 205 cancer line using MTT assay, and four compounds were found to have anticancer activity comparable to that of the marketed drug doxorubicin.
Sodium dodecyl benzene sulfonate-catalyzed reaction for aromatic aldehydes with 1-phenyl-3-methyl-5-pyrazolone in aqueous media
Published in Green Chemistry Letters and Reviews, 2018
Yongjun Zheng, Yong Zheng, Zhen Wang, Yana Cao, Qian Shao, Zhanhu Guo
3-methyl-5-pyrazolone derivatives including 4,4′-arkylmethylene-bis(1-phenyl-3-methyl-5-pyrazolones) have a broad spectrum of approved biological activity, bearing with antiviral (5), anti-inflammatory (6), and antibacterial effect (7). In addition, the corresponding 4,4′-arkylmethylene-bis(1-phenyl-3-methyl-5-pyrazolones) was used as analytical reagents, textile dyes (8), and as ligands for extracting different metal elements (9). The conventional synthesis of 4,4′-arkylmethylene-bis(1-phenyl-3-methyl-5-pyrazolones) involves tandem Knoevenagel-Michael reaction for aromatic aldehydes with two equivalent of 1-phenyl-3-methyl-5-pyrazolone, which can be performed under a variety of reaction conditions (10, 11). In recent years, a wide array of catalysts, such as sodium dodecyl sulfate (12), eletrocatalytic procedure (13), and silica-bonded S-sulfonic acid (14), phosphomolybdic acid (15), 3-aminopropylated silica gel (16), 1,3-disulfonic acid imidazolium tetrachloroaluminate {[Dsim]AlCl4} (17) were employed to synthesize 4,4′-arkylmethylene-bis(1-phenyl-3-methyl-5-pyrazolones). Recently, the synthetic protocol for the 4-substituted pyrazolone derivatives was developed via the one-pot condensation of phenyl hydrazine, ethyl acetoacetate, and aldehydes in the presence of Na+-MMT-[pmim]HSO4 (18) or 2-hydroxy ethylammonium propionate (19). However, some of the methods suffer from long reaction time, harsh reaction conditions, or use of expensive catalysts and organic solvents. In view of the formed colloidal particles in water as an effective, environmentally benign method for organic synthesis and in continuation of our work in the green organic synthesis (20), we investigated the synthesis of 4,4′-phenylmethylene-bis(1-phenyl-3-methyl-5-pyrazolones) with 1-phenyl-3-methyl-5-pyrazolone and benzaldehyde using different surfactants in aqueous medium, and found that sodium dodecyl benzene sulfonate (SDBS) was a most effective catalyst. Consequently, the reaction conditions of the desired product were explored, the results demonstrated that 1:2 molar ratio of benzaldehyde and 1-phenyl-3-methyl-5-pyrazolones reacted for 3 h at about 40°C, in the presence of SDBS as an organocatalyst, which can make organic substance to form colloidal particles in water, and the desired product can be obtained with a 93.0% yield, Then, the catalytic mechanism of SDBS was proposed.
Synthesis, characterisation, biological and theoretical studies of novel pyridine derivatives
Published in Molecular Physics, 2022
P. S. Pradeep Kumar, K. Sunil, B. S. Chethan, N. K. Lokanath, N. Madan, A. M. Sajith
The presence of heterocyclic frameworks in many medicinally relevant molecules of biological importance, material science, agrochemicals, etc. highlights its significance [1–5]. Among the various (hetero) aromatic architectures, pyrazolone core displays a wide range of applications in diverse fields. Consequently, the synthesis of diversely functionalised molecules containing a pyrazolone core is of immense potential for various applications [6,7]. Pyrazolone derivatives have been reported to display a wide spectrum of biological activities such as antimicrobial, anti-fungal, anti-tubercular, anti-inflammatory, anti-convulsant, anticancer, anti-viral, angiotensin converting enzyme (ACE) inhibitory, neuroprotective, cholecystokinin-1 receptor antagonist, and oestrogen receptor (ER) ligand activity, etc [8–12]. Additionally, the presence of this pyrazolone pharmacophore moiety in many FDA approved drugs, highlights its significance in the area of medicinal chemistry (Figure 1). Many pyrazolone derivatives are found in their application as nonsteroidal anti-inflammatory drugs, such as anti-pyrine or phenazone (analgesic and antipyretic), metamizole or dipyrone (analgesic and antipyretic), aminopyrine or aminophenazone (anti-inflammatory, antipyretic, and analgesic), phenylbutazone (anti-inflammatory, antipyretic mainly used in osteoarthritis, rheumatoid arthritis, spondylitis, Reiter's disease), sulfinpyrazone (chronic gout), and oxyphenbutazone (antipyretic, analgesic, anti-inflammatory, mild uricosuric) [12,13]. Many of the heterocyclic compounds and Schiff base derivatives are synthesised by our group and are showing good biological activity [14–19]. Considering the biological relevance of these and pharmaceutically relevant core, our research programme aimed at synthesising novel pyrazolone based analogues, we were interested in synthesising some piperdine fused pyrazolone analogues as potential antibacterial agents. Accordingly, we initiated our synthesis starting from tetrahydro-4H-pyran-4-one which was treated with (tert-Butoxy carbonyl) hydrazine at room temperature in methanol to furnish the tetrahydro-4H-pyran-4ylidene-1,1-dimethylethylester in excellent yields. The structure of this biologically important intermediate was confirmed by 1H NMR, IR, and mass analysis. Further, computational studies were employed to get further insights into the molecular properties of the compounds. The biologically important pharmacophore was then used as the starting point for performing late stage diversification. In this paper, we report the use of acid chlorides on this piperdine fused pyrazolone scaffold to access the respective amide analogues in good yields. The synthesised analogues were further explored for their antimicrobial potential against two gram positive bacterial strains namely S. aureus, and M. luteus, and a gram negative bacterial strain namely E.coli.