The synthesis, computer prediction of the biological activity and the acute toxicity of 4-aryl-5-oxo-4,5-dihydro[1,2,4]triazolo[4,3-a]quinazoline-8-carboxamides

Auteurs-es

  • Svitlana Danylchenko National University of Pharmacy 53 Pushkinska str., Kharkiv, Ukraine, 61002, Ukraine
  • Oleksander Drushlyak National University of Pharmacy 53 Pushkinska str., Kharkiv, Ukraine, 61002, Ukraine
  • Sergiy Kovalenko V. N. Karazin Kharkiv National University 4 Svobody Sq., Kharkiv, Ukraine, 61022, Ukraine
  • Svitlana Kovalenko National University of Pharmacy 53 Pushkinska str., Kharkiv, Ukraine, 61002, Ukraine

DOI :

https://doi.org/10.15587/2313-8416.2016.65166

Mots-clés :

synthesis, 4-aryl-5-oxo-4, 5-dihydro[1, 2, 4]triazolo[4, 3-a]quinazoline-8-carboxamides, computer prediction, biological activity, acute toxicity

Résumé

Aim. The aim of present study was to conduct modelling of the virtual library of 4-aryl-5-oxo-4,5-dihydro[1,2,4]triazolo[4,3-a]quinazoline-8-carboxamides, to determine the most probable biological activity spectrum and the acute toxicity of studied compounds by PASS and GUSAR software, sort out the most perspective substances and develop preparative protocols for their synthesis.

Methods. Using the PASS program computer prediction of the biological activity of 4-aryl-5-oxo-4,5-dihydro[1,2,4]triazolo[4,3-a]quinazoline-8-carboxamides has been performed. Prediction of the acute toxicity has been carried out by the GUSAR software. The structure of the compounds synthesized has been proven by elemental analysis and 1H NMR spectroscopy data.

Results. The synthesis of 4-aryl-5-oxo-4,5-dihydro[1,2,4]triazolo[4,3-a]quinazoline-8-carboxamides has been conducted starting from corresponding methyl 3-aryl-4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazoline-7-carboxylates, which were converted into corresponding 3-aryl-2-hydrazino-4-oxo-3,4-dihydroquinazoline-7-carbohydrazides by treatment with hydrazine hydrate. Heating of these 2-hydrazinoquinazolin-4(3H)-ones with acetylacetone was resulted in 4-aryl-8-[(3,5-dimethyl-1H-pyrazol-1-yl)carbonyl]-1-methyl[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-ones formation. Following substitution of pyrazole moiety by interaction of these compounds with primary amines led to destinated 4-aryl-5-oxo-4,5-dihydro[1,2,4]triazolo[4,3-a]quinazoline-8-carboxamides. The PASS program computer prediction of the biological activity of 4-aryl-5-oxo-4,5-dihydro[1,2,4]triazolo[4,3-a]quinazoline-8-carboxamides has allowed identifying the types of activity of studied compounds and sorting out the leaders with potential antineurotic activity, which are perspective for male reproductive and erectile dysfunction treatment. Prediction of the acute toxicity has been carried out by the GUSAR software, which allowed to refer them to slightly toxic (class 4) or practically nontoxic (class 5) substances.

Conclusions. The obtained compounds are perspective objects for further investigations as slightly toxic (nontoxic) substances with potential antineurotic activity, which are perspective for male reproductive and erectile dysfunction treatment

Bibliographies de l'auteur-e

Svitlana Danylchenko, National University of Pharmacy 53 Pushkinska str., Kharkiv, Ukraine, 61002

Scientific Secretary of scientific and research department

Oleksander Drushlyak, National University of Pharmacy 53 Pushkinska str., Kharkiv, Ukraine, 61002

Candidate of chemical sciences, associate professor

Department of Quality Management

Sergiy Kovalenko, V. N. Karazin Kharkiv National University 4 Svobody Sq., Kharkiv, Ukraine, 61022

Doctor of chemical sciences, professor

Department of Organic Chemistry

Svitlana Kovalenko, National University of Pharmacy 53 Pushkinska str., Kharkiv, Ukraine, 61002

Candidate of chemical sciences, associate professor

Department of Quality Management

Références

Alagarsamy, V., Giridhar, R., Yadav, M. R. (2005). Synthesis and pharmacological investigation of novel 1-substituted-4-phenyl-1,2,4-triazolo[4,3-a]quinazolin-5(4H)-ones as a new class of H1-antihistaminic agents. Bioorganic & Medicinal Chemistry Letters, 15 (7), 1877–1880. doi: 10.1016/j.bmcl.2005.02.016

Alagarsamy, V., Giridhar, R., Yadav, M. R. (2006). Synthesis and pharmacological investigation of novel 1-substituted-4-(4-substituted phenyl)-4 H -[1,2,4]triazolo[4,3- a ]quinazolin-5-ones as a new class of H 1 -antihistamine agents . Journal of Pharmacy and Pharmacology, 58 (9), 1249–1255. doi: 10.1211/jpp.58.9.0012

Alagarsamy, V., Meena, S., Ramaseshu, K. V., Solomon, V. R., Kumar, T. D. A. (2007). 4-Cyclohexyl-1-substituted-4H-[1,2,4]triazolo [4,3-a] quinazolin-5-ones: Novel Class of H 1 -antihistaminic Agents . Chemical Biology & Drug Design, 70 (2), 158–163. doi: 10.1111/j.1747-0285.2007.00544.x

Alagarsamy, V., Solomon, V. R., Murugan, M. (2007). Synthesis and pharmacological investigation of novel 4-benzyl-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as new class of H1-antihistaminic agents. Bioorganic & Medicinal Chemistry, 15 (12), 4009–4015. doi: 10.1016/j.bmc.2007.04.001

Alagarsamy, V., Rupeshkumar, M., Kavitha, K., Meena, S., Shankar, D., Siddiqui, A. A., Rajesh, R. (2008). Synthesis and pharmacological investigation of novel 4-(2-methylphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as new class of H1-antihistaminic agents. European Journal of Medicinal Chemistry, 43 (11), 2331–2337. doi: 10.1016/j.ejmech.2007.10.001

Alagarsamy, V., Kavitha, K., Rupeshkumar, M., Solomon, V., Kumar, J., Kumar, D., Sharma, H. (2009). Synthesis and pharmacological investigation of novel 4-(3-ethylphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a] quinazolin-5-ones as a new class of H1-antihistaminic agents. Acta Pharmaceutica, 59 (1), 97–106 doi: 10.2478/v10007-009-0003-1

Alagarsamy, V., Sharma, H. K., Parthiban, P. et. al. (2009). 4-(3-Methoxyphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones: new class of H1-antihistaminic agents. Pharmazie, 64, 5–9.

Gobinath, M., Subramanian, N., Alagarsamy, V. (2015). Design, synthesis and H1-antihistaminic activity of novel 1-substituted-4-(3-chlorophenyl)-[1,2,4] triazolo [4,3-a] quinazolin-5(4H)-ones. Journal of Saudi Chemical Society, 19 (3), 282–286. doi: 10.1016/j.jscs.2012.02.006

Gobinath, M., Subramanian, N., Alagarsamy, V., Nivedhitha, S., Solomon, V. (2015). Synthesis of 1-Substituted-4-(Pyridin-4-yl) [1,2,4] Triazolo [4,3-a] Quinazolin-5(4H)-ones as a New Class of H1- Antihistaminic Agents. Tropical Journal of Pharmaceutical Research, 14 (2), 271–277. doi: 10.4314/tjpr.v14i2.12

Abdel Gawad, N. M., Georgey, H. H., Youssef, R. M., El Sayed, N. A. (2010). Design, synthesis, and anticonvulsant activity of novel quinazolinone analogues. Medicinal Chemistry Research, 20 (8), 1280–1286. doi: 10.1007/s00044-010-9465-4

Alagarsamy, V., Giridhar, R., Yadav, M., Revathi, R., Ruckmani, K., De Clercq, E. (2006). AntiHIV, antibacterial and antifungal activities of some novel 1,4-disubstituted-1,2,4-triazolo[4,3-a] quinazolin-5(4 h )-ones . Indian J Pharm Sci, 68 (4), 532–535. doi: 10.4103/0250-474x.27840

Patil, S., Patil, S., Jadhav, S., Deshmukh, M. (2010). Synthesis and antimicrobial screening of pyrazolo-3-aryl quinazolin-4(3h)ones. Indian Journal of Pharmaceutical Sciences, 72 (4), 500–504. doi: 10.4103/0250-474x.73934

Gobinath, M., Subramanian, N., Alagarsamy, V. (2012), Anticancer and antitubercular study of some 1,4-disubstituted[1,2,4]-triazolo[4,3-a]quinazolin-5(4H)-ones. International Journal of Research in Pharmaceutical Sciences, 3 (1), 146–149.

Gaudilliere, B., Lavalette, R., Andrianjara, C. (2000). Patent 2792938. Nouvelles 1-aminotriazolo[4,3-a]quinazoline-5-ones inhibitrices de phosphodiesterases IV. France.

Elansary, A. K., Kadry, H. H., Ahmed, E. M.& Sonousi, A. S. M. (2011). Design, synthesis and in vitro PDE4 inhibition activity of certain quinazolinone derivatives for treatment of asthma. Medicinal Chemistry Research, 21 (11), 3327–3335. doi: 10.1007/s00044-011-9846-3

Danylchenko, S. Y., Drushlyak, O. G., Kovalenko, S. S., Kovalenko, S. M. (2015). Formation of 1-methyl[1,2,4]triazolo[4,3-a] quinazolin-5(4H)-ones by reaction of 2-hydrazinoquinazolin-4(3H)-ones with acetylacetone. Heterocyclic Communications, 21 (4), 195–197. doi: 10.1515/hc-2015-0104

Danylchenko, S. Yu., Drushlyak, O. G., Kovalenko, S. S., Kovalenko, S. M. (2015). Formation of 1-methyl[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-ones by reaction of 2-hydrazinoquinazolin-4(3H)-ones with acetylacetone. Heterocyclic Communications, 21 (4), 195–197.

Danilchenko, S. Yu., Drushlyak, O. G., Kovalenko, S. M. (2014). Synthesis of substituted 2-hydrazinoquinazolin-4-ones as intermediates for heterocyclic compounds synthesis. Journal of Organic and Pharmaceutical Chemistry, 12 (3), 66–73.

Saleh, M. A., Abdel-Megeed, M. F., Abdo, M. A., Shkor, A.-B. M. (2003). Synthesis of Aldehydo Sugar (4-oxoquinazolin-2-yl)hydrazones and their transformation into 1-(alditol-1-yl)-1,2,4-triazolo-[4,3-a]quinazolin-5(4H)-ones. Journal of Heterocyclic Chemistry, 40 (1), 85–92. doi: 10.1002/jhet.5570400111

Filimonov, D. A., Lagunin, A. A., Gloriozova, T. A., Rudik, A. V., Druzhilovskii, D. S., Pogodin, P. V., Poroikov, V. V. (2014). Prediction of the Biological Activity Spectra of Organic Compounds Using the Pass Online Web Resource. Chemistry of Heterocyclic Compounds, 50(3), 444–457. doi: 10.1007/s10593-014-1496-1

Filimonov, D. A., Poroikov, V. V. (2006). Prediction of biological activity of organic compounds. Rosiiskii himicheskii zhurnal, 2, 66–75.

Filimonov, D. A., Poroikov, V. V.; Varnek, A., Tropsha, A. (Eds.) (2008). In Chemoinformatics Approaches to Virtual Screening. Cambridge (UK): RSC Publishing, 182–216.

Get more information about biological potential of your compounds. Available at: http://www.pharmaexpert.ru/passonline

Berezovskaya, I. V. (2003). Classification of the chemical parameters on acute toxicity of parenteral routes of administration. Khimiko-Farmatsevticheskii Zhurnal, 37 (3), 32–34.

Lagunin, A., Zakharov, A., Filimonov, D., Poroikov, V. (2011). QSAR Modelling of Rat Acute Toxicity on the Basis of PASS Prediction. Molecular Informatics, 30 (2-3), 241–250. doi: 10.1002/minf.201000151

GUSAR Online. Available at: http://pharmaexpert.ru/GUSAR/acutoxpredict.html

Téléchargements

Publié-e

2016-03-30

Numéro

Rubrique

Pharmaceutical Sciences