Computational Chemistry Of Pyrazole Derivatives: Molecular Modeling, Quantum Mechanical Calculations, And Molecular Dynamics Simulations

Computational Chemistry Of Pyrazole Derivatives: Molecular Modeling, Quantum Mechanical Calculations, And Molecular Dynamics Simulations


  • Subhendu Bikash Jana
  • Kapil Raghuwanshi
  • Gopal Kumar Rai
  • Priyanka Ahlawat
  • S.Reka
  • Pavankumar D Chopade
  • Tulsi Tilva
  • K. Ilango
  • Anil Kumar


Computational chemistry, pyrazole derivatives, molecular modeling, quantum mechanics, drug discovery.


Computational chemistry has become indispensable in elucidating the structural and functional properties of pyrazole derivatives, providing valuable insights into their molecular behavior and interactions. This review examines the role of computational methods, including molecular modeling, quantum mechanical calculations, and molecular dynamics simulations, in the study of pyrazole derivatives. Molecular modeling techniques such as homology modeling and docking studies enable the prediction of binding modes and affinity of pyrazole derivatives to biological targets, while quantum mechanical calculations, particularly density functional theory (DFT), offer detailed insights into their electronic structure and properties. Molecular dynamics simulations further complement these approaches by exploring the dynamic behavior and conformational space of pyrazole derivatives. The implications of computational chemistry for drug discovery and development are significant, offering a cost-effective and efficient means to identify lead compounds, optimize their pharmacological properties, and design novel therapeutics. However, challenges such as the accuracy of force fields and computational scalability persist, highlighting the need for continued research and innovation. Future directions in the field include the development of more accurate force fields, integration of multi-scale modeling approaches, and leveraging emerging technologies such as machine learning to accelerate the discovery of new pyrazole derivatives with therapeutic potential. Overall, computational chemistry holds immense promise in advancing our understanding of pyrazole derivatives and driving innovation in drug discovery and development.


Author Biographies

Subhendu Bikash Jana

Associate Professor, Department of Pharmaceutical Chemistry, Calcutta Institute of Pharmaceutical Technology and Allied Health Sciences, West Bengal, India

Kapil Raghuwanshi

Assistant Professor, Department of Biochemistry, Chhindwara Institute of Medical Sciences, Chhindwara, Madhya Pradesh, India

Gopal Kumar Rai

Associate Professor, Department of Pharmacy, Saroj Institute of Technology and Management, Aahmamau, Sultanpur Road, Lucknow, Uttar Pradesh, India

Priyanka Ahlawat

Research Scholar, Department of Pharmacy, Banasthali Vidyapith, Rajasthan, India


Associate Professor, Department of Pharmaceutical Chemistry, Sree Sastha Pharmacy College, Chembarambakkam, Tamil Nadu, India

Pavankumar D Chopade

Assistant Professor, Department of Pharmaceutical Chemistry, Oriental College of Pharmacy, Sanpada, Navi Mumbai, Maharashtra, India

Tulsi Tilva

Associate Professor, Department of Quality Assurance, Smt. R. D. Gardi College, Nyara, Rajkot, Gujarat, India

K. Ilango

Professor & Principal, Department of Pharmaceutical Chemistry, Tagore College of Pharmacy, Rathinamangalam, Chennai, India

Anil Kumar

Head & Assistant Professor, Department of Chemistry (PG), Sahibganj College Sahibganj, Jharkhand, India


E.S. Nossier, H.H. Fahmy, N.M. Khalifa, W.I. El-Eraky, and M.A. Baset, "Design and synthesis of novel pyrazole-substituted different nitrogenous heterocyclic ring systems as potential anti-inflammatory agents," Molecules, vol. 22, no. 4, p. 512, 2017.

A. Kumar Verma, "Evaluation of anti-inflammatory and analgesic activity of novel pyrazole derivatives," Asian Journal of Biomedical and Pharmaceutical Sciences, vol. 4, no. 37, p. 21, 2014.

R.S. Kumar, I.A. Arif, A. Ahamed, and A. Idhayadhulla, "Anti-inflammatory and antimicrobial activities of novel pyrazole analogues," Saudi journal of biological sciences, vol. 23, no. 5, pp. 614-620, 2016.

H. B’Bhatt and S. Sharma, "Synthesis and antimicrobial activity of pyrazole nucleus containing 2-thioxothiazolidin-4-one derivatives," Arabian Journal of Chemistry, vol. 10, pp. S1590-S1596, 2017.

J.J. Bhatt, K.D. Suresh, and H.T. Mrugesh, "Synthesis, characterization and antimicrobial activity of pyrazole capped 2-azitidinone derivatives," RJLBPCS, vol. 5, no. 1, pp. 647-662, 2019.

F. Chaudhry et al., "In search of new α-glucosidase inhibitors: Imidazolylpyrazole derivatives," Bioorganic chemistry, vol. 71, pp. 102-109, 2017.

A.M. Asiri and S.A. Khan, "Synthesis, characterization, and in vitro antibacterial activities of macromolecules derived from bis‐chalcone," Journal of Heterocyclic Chemistry, vol. 49, no. 6, pp. 1434-1438, 2012.

P. Uma, K.C. Rajanna, F. Unnisa, and P.K. Saiprakash, "Synthesis, characterization and biological activity studies of certain 1-((benzo [d] thiazol-2-yl) methyl)-4, 5-dihydro-3-methyl-N-phenyl-1H-pyrazol-5-imine and 2-((5-aryl-1H-1, 2, 4-triazol-3-yl) methyl) benzo [d] thiazoles," Cogent Chemistry, vol. 3, no. 1, p. 1312673, 2017.

E.A. Orabi, M.A. Orabi, M.H. Mahross, and M. Abdel-Hakim, "Computational investigation of the structure and antioxidant activity of some pyrazole and pyrazolone derivatives," Journal of Saudi Chemical Society, vol. 22, no. 6, pp. 705-714, 2018.

H. Brahmbhatt, M. Molnar, and V. Pavić, "Pyrazole nucleus fused tri-substituted imidazole derivatives as antioxidant and antibacterial agents," Karbala International Journal of Modern Science, vol. 4, no. 2, pp. 200-206, 2018.

F.Q. Wang et al., "A novel domino approach for synthesis of indolyl tetrahydropyrano [4, 3-c] pyrazole derivatives as anticancer agents," Tetrahedron, vol. 72, no. 38, pp. 5769-5775, 2016.

F.K. Keter and J. Darkwa, "Perspective: the potential of pyrazole-based compounds in medicine," Biometals, vol. 25, no. 1, pp. 9-21, 2012.

A. Ghafoor, N. Aslam, M.C. Elliott, N. Sajid, M. Nasrullah, M. Ashraf, Q.U. Ain, and M.A. Khan, "Synthesis, characterization and biological evaluation of some new oxino bis-pyrazole derivatives," Asian Journal of Chemistry, vol. 28, no. 8, pp. 1648-1652, 2016.

H. Dai, S. Ge, J. Guo, S. Chen, M. Huang, J. Yang, S. Sun, Y. Ling, and Y. Shi, "Development of novel bis-pyrazole derivatives as antitumor agents with potent apoptosis induction effects and DNA damage," European journal of medicinal chemistry, vol. 143, pp. 1066-1076, 2018.

M.B. GÜRDERE, E. KAMO, Y. Budak, A.Ş. YAĞLIOĞLU, and M. Ceylan, "Synthesis and anticancer and cytotoxic effects of novel 1, 4-phenylene-bis-N-thiocarbamoylpyrazole and 1, 4-phenylene-bis-pyrazolylthiazole derivatives," Turkish Journal of Chemistry, vol. 41, no. 2, pp. 179-189, 2017.

L. Knorr, "Einwirkung von acetessigester auf phenylhydrazin," Berichte der deutschen chemischen Gesellschaft, vol. 16, no. 2, pp. 2597-2599, 1883.

H.V. Pechmann, "Ueber Diazomethan," Berichte der deutschen chemischen Gesellschaft, vol. 27, no. 2, pp. 1888-1891, 1894.

D.C. Pinto, A.M. Silva, J.A. Cavaleiro, and J. Elguero, "New bis (chalcones) and their transformation into bis (pyrazoline) and bis (pyrazole) derivatives," European Journal of Organic Chemistry, vol. 2003, no. 4, pp. 747-755, 2003.

E. Bisenieks, J. Uldrikis, and G. Duburs, "Reaction of 3, 5-carbonyl-substituted 1, 4-dihydropyridines with hydrazine hydrate," Chemistry of Heterocyclic Compounds, vol. 40, no. 7, pp. 869-875, 2004.

Dharmendra Bhati et al., “FUSED AND SUBSTITUTED PYRIMIDINE DERIVATIVES AS POTENT ANTICANCER AGENTS,” Biochemical and Cellular Archives/Biochemical and cellular archives, vol. 24, no. 1, Jan. 2024, doi:

K. J. Mangala et al., “NANOCELLULOSE: A VERSATILE AND SUSTAINABLE CARRIER FOR DRUG AND BIOACTIVE COMPOUNDS,” Biochemical and Cellular Archives/Biochemical and cellular archives, vol. 24, no. 1, Jan. 2024, doi:

Rohit Kumar Trivedi et al., “REVOLUTIONIZING DRUG DELIVERY THROUGH 3D PRINTING TECHNOLOGY: CURRENT ADVANCES AND FUTURE DIRECTIONS,” Biochemical and Cellular Archives/Biochemical and cellular archives, vol. 24, no. 1, Jan. 2024, doi:

H. Rastogi, P. Bhatt, S. Garg, S. Kamboj, V. Deva, and R. Goel, “EXPLORING THE POTENTIAL OF QUANTUM DOTS AS LUMINOUS PROBES FOR TARGETED DRUG DELIVERY AND BIOIMAGING IN CLINICAL DIAGNOSTICS,” Biochemical and Cellular Archives/Biochemical and cellular archives, vol. 24, no. 1, Jan. 2024, doi:

M. shama, “CRISPR-Cas9 gene editing in pharmaceuticals: Current applications and future prospects,” Biochemical and Cellular Archives/Biochemical and cellular archives, vol. 23, no. S1, Dec. 2023, doi:

S. Arora, Saiphali, G. Dharmamoorthy Dharmendra Bhati, T. Gupta, and P. Bhatt, “Advancements in peptide-based therapeutics: Design, synthesis and clinical applications,” Biochemical and Cellular Archives/Biochemical and cellular archives, vol. 23, no. S1, Dec. 2023, doi:

M. Singhal et al., "Formulation development and characterization of powder for oral suspension containing H2 blocker drug to combat GERD and peptic ulcer," NeuroQuantology, vol. 20, no. 11, pp. 1258, 2022.

S.A.G. Abdel-Aziz, T.E.S. Ali, K.M. El-Mahdy, and S.M. Abdel-Karim, "Synthesis and antimicrobial activities of some novel bis-pyrazole derivatives containing a hydrophosphoryl unit," European Journal of Chemistry, vol. 2, no. 1, pp. 25-35, 2011.

M.J. Hayter, D.J. Bray, J.K. Clegg, and L.F. Lindoy, "New bis‐Pyrazole Derivatives Synthesized From Aryl‐and Xylyl‐Linked bis (β‐Diketone) Precursors," Synthetic communications, vol. 36, no. 6, pp. 707-714, 2006.

P.S. Nayak, B. Narayana, B.K. Sarojini, J. Fernades, B.R. Bharath, and L.N. Madhu, "Synthesis, molecular docking and biological evaluation of novel bis-pyrazole derivatives for analgesic, anti-inflammatory and antimicrobial activities," Medicinal Chemistry Research, vol. 24, no. 12, pp. 4191-4206, 2015.

A.A. Baoum, R.S. Alsulami, and H.M. Faidallah, "Synthesis and Biological Evaluation of some bis-pyrazole derivatives as Anticancer Agents," International journal of research in medical and basic sciences, vol. 3, pp. 2455-2569, 2017.

R.S. Dhivare and S.S. Rajput, "Microwave supported synthesis and antimicrobial evaluation of bis-pyrazole derivatives from N-phenyl glutarimides," International letters of Chemistry Physcics and Astronomy, vol. 65, pp. 53-63, 2016.

N.H. Metwally, F.M. Abdelrazek, and M.T. Jaafar, "Synthesis and Antimicrobial Activity of Some Novel Substituted Bis‐Pyridone, Pyrazole, and Thiazole Derivatives," Journal of Heterocyclic Chemistry, vol. 52, no. 2, pp. 358-365, 2015.

R. Czarnomysy et al., "A novel series of pyrazole-platinum (II) complexes as potential anti-cancer agents that induce cell cycle arrest and apoptosis in breast cancer cells," Journal of enzyme inhibition and medicinal chemistry, vol. 33, no. 1, pp. 1006-1023, 2018.

S. Du et al., "Synthesis, antifungal activity and structure-activity relationships of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides," Molecules, vol. 20, no. 5, pp. 8395-8408, 2015.

R. Nagamallu, B. Srinivasan, M.B. Ningappa, and A.K. Kariyappa, "Synthesis of novel coumarin appended bis (formyl pyrazole) derivatives: Studies on their antimicrobial and antioxidant activities," Bioorganic & medicinal chemistry letters, vol. 26, no. 2, pp. 690-694,

S. Ahamed, P. Bhatt, S. J. Sultanuddin, R. Walia, M. A. Haque, and S. B. InayathAhamed, "An Intelligent IoT enabled Health Care Surveillance using Machine Learning," in 2022 International Conference on Advances in Computing, Communication and Applied Informatics (ACCAI), IEEE, 2022.

V. Ahmed, S. Sharma, and P. Bhatt, "Formulation and evaluation of sustained release tablet of diltiazem hydrochloride," International Journal of Pharmaceutical Sciences and Research, vol. 11, no. 5, pp. 2193-2198, 2020.

A. E. Al-Snafi, S. Singh, P. Bhatt, and V. Kumar, "A review on prescription and non-prescription appetite suppressants and evidence-based method to treat overweight and obesity," GSC biol pharm sci, vol. 19, no. 3, pp. 148–155, 2022.

B. Baskar, S. Ramakrishna, and A. Daniela La Rosa (Eds.), Encyclopedia of green materials. Singapore: Springer Nature Singapore, 2022.

P. Bhatt, A. Kumar, and R. Shukla, "Nanorobots recent and future advances in cancer or dentistry therapy- A review," Am J PharmTech Res, vol. 9, no. 3, pp. 321–331, 2019.

P. Bhatt, V. Kumar, M. K. Malik, and T. Kumar, "Citrus Flavonoids: Recent Advances and Future Perspectives On Preventing Cardiovascular Diseases," in The Flavonoids, pp. 131-152, 2024.

P. Bhatt et al., "Functional and tableting properties of alkali-isolated and phosphorylated barnyard millet (Echinochloa esculenta) starch," ACS Omega, vol. 8, no. 33, pp. 30294–305, 2023.

P. Bhatt et al., "Plasma modification techniques for natural polymer-based drug delivery systems," Pharmaceutics, vol. 15, no. 8, pp. 2066, 2023.

P. Bhatt, S. Singh, S. K. Sharma, and S. Rabiu, "Development and characterization of fast dissolving buccal strip of frovatriptan succinate monohydrate for buccal delivery," Int J Pharm Investig, vol. 11, no. 1, pp. 69–75, 2021.

P. Bhatt et al., "Artificial intelligence in pharmaceutical industry: Revolutionizing drug development and delivery," The Chinese Journal of Artificial Intelligence, 2023.

P. Bhatt, S. Singh, S. Sharma, and V. Kumar, "Blockchain technology applications for improving quality of electronic healthcare system," in Blockchain for Healthcare Systems, pp. 97–113, CRC Press, 2021.

P. Bhatt, "Mouth Dissolving Tablets Challenges, Preparation Strategies with a Special Emphasis on Losartan Potassium–A Review," World J. Pharm. Pharm. Sci, vol. 7, no. 9, pp. 271-287, 2018.

C. Goyal et al., "Estimation of shelf-life of Balachaturbhadrika syrup containing different sweetening agents," Res J Pharm Technol, pp. 5078–5083, 2022.

T. Kaur and S. Singh, "Controlled release of bi-layered malvidin tablets using 3D printing techniques," J Pharm Res Int, pp. 70–78, 2021.

M. Kaurav et al., "In-depth analysis of the chemical composition, pharmacological effects, pharmacokinetics, and patent history of mangiferin," Phytomed Plus, vol. 3, no. 2, pp. 100445, 2023.

A. Kumar, P. Bhatt, and N. Mishra, "Irritable bowel Syndrome with reference of Alosetron Hydrochloride and Excipient profile used in the manufacturing of Alosetron tablet-A review," J Chem Pharm Sci, vol. 12, no. 03, pp. 71–78, 2019.

M. K. Malik, P. Bhatt, and T. Kumar, "Significance of chemically derivatized starch as drug carrier in developing novel drug delivery devices," Nat Prod J, vol. 12, 2022.

M. K. Malik et al., "Preclinical safety assessment of chemically cross-linked modified mandua starch: Acute and sub-acute oral toxicity studies in Swiss albino mice," ACS Omega, vol. 7, no. 40, pp. 35506–35514, 2022.

M. K. Malik et al., "Phosphorylation of alkali extracted mandua starch by STPP/STMP for improving digestion resistibility," ACS Omega, vol. 8, no. 13, pp. 11750–11767, 2023.

Pankaj, "Anti-cancer cyclodextrin nanocapsules based formulation development for lung chemotherapy," J Pharm Res Int, pp. 54–63, 2021.

Y. Xu, Q. Chen, Y. Tian, W. Wu, Y. You, and Z. Weng, "Silver-catalyzed synthesis of 5-aryl-3-trifluoromethyl pyrazoles," Tetrahedron Lett., vol. 61, p. 151455, 2020.

J. Poletto, G. M. Ribeiro, M. J. V. Da Silva, A. P. Jacomini, E. A. Basso, D. F. Back, S. Moura, and F. A. Rosa, "One-Pot Highly Regioselective Synthesis of α-Ketoamide N-Arylpyrazoles from Secondary β-Enamino Diketones," Org. Lett., vol. 21, pp. 6325–6328, 2019.

J. K. Kim, M. Gong, E. A. Shokova, V. A. Tafeenko, O. V. Kovaleva, Y. Wu, and V. V. Kovalev, "Pyrazoles: ‘one-pot’ synthesis from arenes and carboxylic acids," Org. Biomol. Chem., vol. 18, pp. 5625–5638, 2020.

Y. R. Girish, K. S. S. Kumar, H. S. Manasa, and S. Shashikanth, "ZnO: An Ecofriendly, Green Nano-catalyst for the Synthesis of Pyrazole Derivatives under Aqueous Media," J. Chin. Chem. Soc., vol. 61, pp. 1175–1179, 2014.

F. Gosselin, P. O’Shea, R. Webster, R. Reamer, R. Tillyer, and E. Grabowski, "Highly Regioselective Synthesis of 1-Aryl-3,4,5-Substituted Pyrazoles," Synlett, vol. 2006, pp. 3267–3270, 2006.

S. T. Heller and S. R. Natarajan, "1,3-Diketones from Acid Chlorides and Ketones: A Rapid and General One-Pot Synthesis of Pyrazoles," Org. Lett., vol. 8, pp. 2675–2678, 2006.

A. S. Komendantova, K. A. Lyssenko, I. V. Zavarzin, and Y. A. Volkova, "Iodine-promoted synthesis of pyrazoles from 1,3-dicarbonyl compounds and oxamic acid thiohydrazides," Org. Chem. Front., vol. 7, pp. 1640–1646, 2020.

G. Yang, Y. Liu, X. Lin, B. Ming, K. Li, and C. Hu, "Self-assembly of a new 3D platelike ternary-oxo-cluster: An efficient catalyst for the synthesis of pyrazoles," Chin. Chem. Lett., vol. 33, pp. 354–357, 2022.

H. S. Chandak, N. P. Lad, and D. S. Dange, "Greener and facile aqueous synthesis of pyrazoles using Amberlyst-70 as a recyclable catalyst," Green Chem. Lett. Rev., vol. 5, pp. 135–138, 2012.

Y.-F. Liu, K. Li, H.-Y. Lian, X.-J. Chen, X.-L. Zhang, and G.-P. Yang, "Self-Assembly of a U(VI)-Containing Polytungstate Tetramer with Lewis Acid-Base Catalytic Activity for a Dehydration Condensation Reaction," Inorg. Chem., vol. 61, pp. 20358–20364, 2022.

A. Corradi, C. Leonelli, A. Rizzuti, R. Rosa, P. Veronesi, R. Grandi, S. Baldassari, and C. Villa, "New 'Green' Approaches to the Synthesis of Pyrazole Derivatives," Molecules, vol. 12, pp. 1482–1495, 2007.

Y. R. Huang and J. A. Katzenellenbogen, "Regioselective Synthesis of 1,3,5-Triaryl-4-alkylpyrazoles: Novel Ligands for the Estrogen Receptor," Org. Lett., vol. 2, pp. 2833–2836, 2000.

Pankaj, "Cyclodextrin modified block polymer for oral chemotherapy," J Pharm Res Int, pp. 21–29, 2021.

V. Raghuwanshi et al., "Recent Advances In Nanotechnology For Combating Against Corona Virus Infection," Journal of Pharmaceutical Negative Results, pp. 1811-1820, 2022.

K. K. Sahu et al., "Utility of nanomaterials in wound management," in Nanotechnological Aspects for Next-Generation Wound Management, Elsevier, pp. 101–130, 2024.

S. K. Sharma et al., "Combined therapy with ivermectin and doxycycline can effectively alleviate the cytokine storm of COVID-19 infection amid vaccination drive: A narrative review," J Infect Public Health, vol. 15, no. 5, pp. 566–572, 2022.

S. K. Sharma and P. Bhatt, "Controlled release of bi-layered EGCG tablets using 3D printing techniques," J Pharm