Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Articles

Vol. 2 No. 4 (2011): October-December 2011

Topliss Modified Approach for Design and Synthesis of 1,3 Thiazines as Antimicrobials

DOI
https://doi.org/10.37285/ijddd.2.4.4
Submitted
December 9, 2024
Published
2024-12-09

Abstract

In the series of 6-[4-substitutedphenyl]-4-phenyl-6H-1,3-thiazine-2-amines and N-[6-(4-substitutedphenyl)-
4-phenyl-6H-1,3-thiazine-yl]acetamides, substituents at fourth position of the phenyl ring were selected according to the Topliss modified approach and synthesized initial set of compounds. The antimicrobial screening revealed that compounds with methoxy substituent having negative sigma (-0.04) and negative pi (-0.27) values are good antimicrobials showing low minimum inhibitory concentration (MIC). Based on the observation hydroxyl group with more negative sigma (-0.61) and pi (-0.37) values was selected to synthesize second set compounds and were found better antimicrobials than the initial set of compounds. The study revealed that electron donating polar substituents at fourth position of the phenyl ring are required to improve antimicrobial potential in the series of 6-[4-substitutedphenyl]-4-phenyl-6H-1,3-thiazine-2-amines and N-[6-(4-substitutedphenyl)-4-phenyl-6H-1,3-thiazine-yl]acetamides.

References

  1. [1] Koketsu, M.; Tanaka, K.; Takenaka, Y.; Kwong, C.D.; Ishihara, H. Synthesis of 1,3- Thiazin Derivatives and Their Evaluation as Potential Antimycobacteruial Agents. Eur. J. Pharm. Sci., 2002, 15, 307-310.
  2. [2] Bozsing, D.; Sohar, P.; Gigler, G.; Kovacs, G. Synthesis and Pharmacological Study of New 3,4-Dihydro-2H,6H-pyrimido(2,1-b) (1,3)thiazines. Eur. J. Med. Chem., 1996, 31, 663-668.
  3. [3] Tozkoparan, B.; Aktay, G.; Erdem, Y. Synthesis of Some 1,2,4-Triazolo[3,2-B]-1,3-Thiazine-7-ones with Potential Analgesic and Antiinflammatory Activities. II Farmaco., 2002, 57, 145–152.
  4. [4] Koketsua, M.; Tanakaa, K.; Takenakaa, Y.; Kwongb, C.D.; Ishiharaa, H. Synthesis of 1,3-Thiazine Derivatives and Their Evaluation as Potential Antimycobacterial Agents. Eur. J. Pharma. Sci., 2002, 15, 307–310.
  5. [5] Suarez, M.; Novoa, H.; Verdecia, Y.; Ochoa, E.; Alvarez, A.; Roberto, R.; Alvarez, M.; Dolores, M.; Seoane, C.; Norbert, M.B.; Oswald, M.P.; Nazario, M.; et al. A Straight Forward Synthesis and Structure of Unprecedented Iminium Salts of Dihydropyrido[3,2-E][1,3]thiazines. Tetrahedron, 2006, 62, 1365–1371.
  6. [6] Tung-Mei, T.; Wen-Chuan, H. Condensed Naphtho [1,8-De][1,3] Thiazines 2. An Orientating Structure Modification of Naphtho [1,8-De][1,2,4]- Triazolo [3,4-B][1,3] Thiazine Ring System. Chin. Pharma. J., 2005, 57,43- 48.
  7. [7] Trofimova, T.P.; Zefirova, O.N.; Mandrugin, A.A.; Fedoseev, V.M.; Peregud, D.I.; Onufriev, M.V.; Gulyaeva,
  8. N. V; Proskuryakov, S.Y. Synthesis and Study of NOS-Inhibiting Activity of 2-N-Acylamino-5,6-dihydro-4H-1,3-thiazine. Moscow. Univ. Chem. Bull., 2008, 63, 274–277.
  9. [8] Kulkarni, V.M.; Bothara, K.G. Drug Design, Nirali Prakashan, Pune, 2006, 4th edn. 211.
  10. [9] Wone, D.W.; Rowley, J.A.; Garofalo, A.W.; Berkman, C.E. Optimizing Phenylethylphosphonamidates for the Inhibition of Prostate-specific Membrane Antigen. Bioorg. Med. Chem., 2006, 14, 67-76.
  11. [10] Quaglia, W.; Santoni, G.; Pigini, M.; Piergentili, A.; Gentili, F.; Buccioni, M.; Mosca, M.; Lucciarini, R.; Nabissi, M.; Ballarini, P.; Poggesi, E.; Leonardi, A.;Giannella, M. Structure-activity Relationships in 1,4-Benzodioxan-related Compounds. J. Med. Chem., 2005, 48, 7750-7763.
  12. [11] Rando, D.G.; Sato, D.N.; Siqueira, L.; Malvezzi, A.; Leite,
  13. C. Q.F.; Amaral, A.T. Potential Tuberculostatic Agents. Topliss Application on Benzoic Acid [(5-Nitro-thiophen-2-yl)-methylene]-hydrazide Series. Bioorg. Med. Chem., 2002 10, 557-560.
  14. [12] Bhatia, M.S.; Choudhari, P.B.; Ingale, K.B.; Zarekar, B.E. Synthesis, Screening and QSAR Studies of 2, 4-Disubstituted1,5-Benzodiazepine Derivative. Indian Drugs, 2009, 46, 196-201.
  15. [13] Furniss, B.S.; Tatchell, A.R.; Hannaford, A.J.; Smith, P.W.G. Vogel’s, Textbook of Practical Organic Chemistry, Pearson Education, New Delhi, 2008, 5th edn., 1034.
  16. [14] Kulirajan, R.; Sivakumar, S.U.; Jubie, S.; Gowramma, B.; Suresh, B. Synthesis and Biological Evaluation of Some Heterocyclic Derivatives of Chalcones. Int. J. Chem. Tech. Res., 2009, 1, 27-34.
  17. [15] Sawant, R.L.; Bhatia, M.S. QSAR Analysis of 2-Oxo-1,2,3,4-Tetrahydropyrimidine Analogues of Antibacterials, Collect. Czech. Chem. Commun., 2009, 74, 1361-1373.

Similar Articles

<< < 2 3 4 5 6 7 

You may also start an advanced similarity search for this article.