Author(s): Gurdeep Singh, Ritesh Patel, Sudeep Mandal, Deepak Kumar Basediya


DOI: 10.52711/0974-360X.2021.01148   

Address: Gurdeep Singh1*, Ritesh Patel2, Sudeep Mandal3, Deepak Kumar Basediya4
1School of Pharmaceutical Science Lovely Professional University Phagwara, Punjab- 144001, India.
2Department of Pharmaceutical Chemistry, Indore Institute of Pharmacy, Indore-453331, M. P., India.
3Faculty of Pharmacy, Kalinga University, Raipur-492101, C.G., India.
4Department of Pharmacy, Technocrats Institute of Technology, Bhopal-462021, M. P., India.
*Corresponding Author

Published In:   Volume - 14,      Issue - 12,     Year - 2021

A series of substituted 4-{1-aza-2-[(aryl) amino)]}-3-methyl-2-pyrazolin-5-ones has been synthesized and evaluated for their biological activity. The title compounds (4a-l) were prepared by the diazotization of substituted anilines (1a-l) to form substituted phenyl hydrazine derivatives (2a-l) which synthesized substituted 4-{1-aza-2-[(aryl) amino)]}-3-methyl-2-pyrazolin-5-ones (4a-l) by Michael addition reaction, which is a nucleophilic addition of enolate anion to the carbon-carbon double bond of a a, ß–unsaturated carboxylic acid derivatives. Twelve different pyrazolinone derivatives (4a to 4l) were synthesized. Structural assignments of these compounds have been made by elemental analysis, FTIR, 1HNMR and Mass spectral data and the purity of the compounds was determined by TLC. The antimicrobial activity of the newly Synthesized heterocyclic compounds were evaluated against Gram-positive, Gram-negative bacteria and fungi. Most of the compounds showed a moderate degree of potent antimicrobial activity. While analgesic activities were tested via both hot plate and acetic acid induced writhing methods. The study concluded that the compound 4b and4f were found to exhibit significant analgesic activity when compared to Diclofenac as standard drug while other derivatives exhibit moderate to good analgesic activity.

Cite this article:
Gurdeep Singh, Ritesh Patel, Sudeep Mandal, Deepak Kumar Basediya. Synthesis, characterization and biological evaluation of 4-{1-aza-2-[(aryl) amino]}-3-methyl-2-pyrazolin-5-ones derivatives. Research Journal of Pharmacy and Technology. 2021; 14(12):6645-2. doi: 10.52711/0974-360X.2021.01148

Gurdeep Singh, Ritesh Patel, Sudeep Mandal, Deepak Kumar Basediya. Synthesis, characterization and biological evaluation of 4-{1-aza-2-[(aryl) amino]}-3-methyl-2-pyrazolin-5-ones derivatives. Research Journal of Pharmacy and Technology. 2021; 14(12):6645-2. doi: 10.52711/0974-360X.2021.01148   Available on:

1.    Li Q, Mitscher LA and Shen LL. The 2-pyridone antibacterial agents: bacterial topoisomerase inhibitors. Medicinal Research Reviews 2000; 20:231–293.
2.    Fassihi A, Abedi D and Saghaie L: Synthesis, antimicrobial evaluation and QSAR study of some 3-hydroxy-pyridine-4-one and 3-hydroxypyran-4-one derivatives. European Journal of Medicinal Chemistry 2009; 44:2145–2157.
3.    Bildirici I, Sener A, Tozlu I. Further derivatives of 4-benzoyl- 1, 5-diphenyl-1H-pyrazole-3-carboxylic acid and their antibacterial activities. Medicinal Research Reviews2007; 16: 418–426.
4.    Mate GS, Naikwade NS, Chowki CSAA, Patil SB. Evaluation of anti-nociceptive activity of Cissusquandrangularis on albino mice, Int. J. Green Pharm.; 2:118-121, 2008.
5.    Olgart L, Kerezondius NP. Nerve pulp interactions, Arch Oral Biol.; 39: 47-54, 1994.
6.    Kang JD, Georgescus HI, Meityrelarkin D. Herniated cervical intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6 and prostaglandin E2, Spine; 21:271-277, 1996.
7.    Palmgreen J, Gronbald M, Virri J. Immuno-histochemical demonstration of sensory and autonomic nerve terminals in herniated lumbar disc tissue, Spine; 100: 10-15, 1996.
8.    Malmberg AB, Yaksh TL. Spinal nitric oxide synthasis inhibition blocks NMDA- induced thermal hyperalgesia and produces antinociception in the formalin tests in rats, Pain; 54: 291-300, 1993.
9.    Ignarro LJ, Aeberhard FE, Henderson SA. The biology of nitric oxide, E.A.; 3:5th ed. London, Portland, 1996.
10.    Fustero S, Sanchez-Rosello M, Barrio P and Simon-Fuentes A. From 2000 to Mid-2010: a fruitful decade for the synthesis of pyrazoles. Chemistry Reviews 2011; 111: 6984–7034.
11.    Ibrahim HS, Abou-Seri SM, Tanc M, Elaasser MM, Abdel-Aziz HA and Supuran CT. Isatin-pyrazole benzenesulfonamide hybrids potently inhibit tumor-associated carbonic anhydrase isoforms.European Journal of Medicinal Chemistry 2015; 103: 583–593.
12.    Reddy TS, Kulhari H, Reddy VG, Bansal V, Kamal A and Shukla R. Design, synthesis and biological evaluation of 1, 3-diphenyl-1H-pyrazole derivatives containing benzimidazole skeleton as potential anticancer and apoptosis inducing agents. European Journal of Medicinal Chemistry 2015; 101: 790–805.
13.    Kucukguzel SG and Senkardes S. Recent advances in bioactive pyrazoles. European Journal of Medicinal Chemistry 2014; 97(5): 786–815.
14.    Raffa D, Maggio B, Raimondi MV, Cascioferro S, Plescia F, Cancemi G and Daidone G. Recent advanced in bioactive systems containing pyrazole fused with a five membered heterocycle. European Journal of Medicinal Chemistry 2014; 97(5): 732–746.
15.    Bildirici I, Sener A, Atalan E, Battal AH and Genc H. Synthesis and antibacterial activity of 4-benzoyl-1-(4-carboxy-phenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid and derivatives. Medicinal Chemistry 2009; 18: 327–340.
16.    Srikantamurthy N, Umesha KB, Shridevi DD, Shulbakara K and Chethan J. Novel pyrazole integrated 1, 3, 4- oxadiazoles: synthesis, characterization and antimicrobial evaluation. Bioorganic Medicinal Chemistry 2014; 24(1): 245–248.
17.    Baraldi PG, Manfredini S, Romagnoli R, Stevanato L, Zaid AN and Manservigi R. Synthesis and anti-HSV-1 activity of 6 substituted pyrazolo[3, 4-d]pyridazin-7-one nucleosides. Nucleosides Nucleotides 1998; 17: 2165.
18.    Rashad AE, Hegab MI, Abdel-Megeid RE, Micky JA and Abdel-Megeid FM. Synthesis and antiviral evaluation of some new pyrazole and fused pyrazolo-pyrimidine derivatives. Bioorganic Medicinal Chemistry 2008; 16(15) : 7102–7106.
19.    Balbi A, Anzaldi M, Maccio C, Aiello C, Mazzei M, Gangemi R, Castagnola P, Miele M, Rosano C and Viale M. Synthesis and biological evaluation of novel pyrazole derivatives with anticancer activity. European Journal of Medicinal Chemistry2011; 46: 5293– 5309.
20.    Kamal A, Shaik AB, Jain N, Kishor C, Nagabhushana A, Supriya B, Chourasiya SS, Suresh Y, Mishra KR and Addlaganatta A. Design and synthesis of pyrazole–oxindole conjugates targeting tubulin polymerization as new anticancer agents. European Journal of Medicinal Chemistry2015; 92: 501–513.
21.    Gokhan-Kelekci N, Yabanoglu S, Kupeli E, Salgin U, Ozgen O, Ucar G, Yesilada E, Kendi E and Yesilada A and Bilgin AA. A new therapeutic approach in Alzheimer disease: some novel pyrazole derivatives as dual MAO-B inhibitors and antiinflammatory analgesics. Bioorganic Medicinal Chemistry 2007; 15: 5775– 5786.
22.    Badawey E and El-Ashmawey IM: Nonsteroidal anti-inflammatory agents-Part 1. anti-inflammatory, analgesic and antipyretic activity of some new 1-(pyrimidin-2-yl)-3-pyrazolin- 5-ones and 2-(pyrimidin-2-yl)-1, 2, 4, 5, 6, 7-hexahydro-3Hindazol-3-ones. European Journal of Medicinal Chemistry 1998; 33: 349.
23.    Mishra PD, Wahidullah S and Kamat SY. A heteroaromatic acid from marine sponge Suberites vestigium. Indian Journal of Chemistry Sec. B 1998; 37: 199.
24.    Colliot F, Kukorowski KA, Hawkins DW and Roberts DA. Fipronil: a new soil and foliar broad spectrum insecticide, Brighton Crop Protection Conferences: Pests and Diseases 1992; 1: 29–34.
25.    Chen HS, Li ZM and Han YF. Synthesis and fungicidal activity against Rhizoctonia solani of 2-alkyl (alkylthio)-5-pyrazolyl- 1, 3, 4-oxadiazoles (thiadiazoles), Journal of Agriculture and Food Chemistry 2000; 48: 5312–5315.
26.    Kurowski M, Dunky A and Geddawi M. Transsynovial distribution and protein binding of pirazolac in patients with rheumatoid arthritis, European Journal of Clinical Pharmacology 1986; 31: 307– 311.
27.    Lepage F and Hublot B. European Patent Application EP 459 887, Chemistry Abstract 1992; 116:128917.
28.    Bailey DM, Hansen PE, Hlavac AG, Baizman ER, Pearl J, DeFelice AF and Feigenson ME. 3, 4-Diphenyl-1H-pyrazole-1- propanamine antidepressants, Journal of Medicinal Chemistry1985; 28(2): 256– 260.
29.    Wiley RH and Wiley P. Pyrazolones, Pyrazolidones and Derivatives. John Wiley and sons, New York 1964: 102.
30.    Mert S, Kasımogullari R, T Ica T, Colak F, Altun A, Ok S. Synthesis, structure activity relationships, and in vitro antibacterial and antifungal activity evaluations of novel pyrazole carboxylic and dicarboxylic acid derivatives, European Journal of Medicinal Chemistry 2014; 78: 86–96.
31.    Furnis BS, Hannaford AJ, Smith PG andTatchell AR. Vogel’s Textbook of Practical Organic Chemistry. Pearson Education, Essex, UK, 5th edition, 2005.
32.    Saravanan G, Pannerselvam P, Chinnasamy RPr. Synthesis and antimicrobial screening of novel Schiff bases of 3-amino-2-methyl quinazolin-4(3H)-one. Journal of Advanced Pharmaceutical Technology and Research, 2016, September; 1(3): 320-325.
33.    Nehal A. Hamdy, et al. “Potent anti-inflammatory and analgesic activities of new derivatives of chalcone, pyridine, pyrazole and isoxazole incorporated into 5, 6, 7, 8- tetrahydronaphthalene”. Egyptian Pharmaceutial Journal, 11(1) (2012):22-30.
34.    Ravi Kiran B., et al. “Synthesis, evaluation of analgesic and anti-inflammatory activities of substituted 1, 2-Benzoxazolone and 3-Chloro-1, 2-Benzoxazole derivatives”. International Journal of Pharmaceutical Science and Research, 6(7) (2015):2918-2925.
35.    Kasabe Amit J, et al. “Synthesis, anti-tubercular and analgesic activity evaluation of new 3-pyrazoline derivatives”. International Journal of Pharmacy and Pharmaceutical Sciences, 2(2) (2010):132-135.
36.    Collier HO, et al. “The abdominal constriction response and its suppression by analgesic drug in the mouse”. Br. J. Pharmacol. Chemother., 32 (1968):295-310.

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