Designing and Synthesis of New Fluorine Substituted Pyrimidine-Thion-5-Carbonitriles and the Related Derivatives as Photochemical Probe Agents for Inhibition of Vitiligo Disease

Mohammed S. T. Makki, Dina A. Bakhotmah, Reda M. Abdel-Rahman, Mohammed S. El-Shahawy

Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

DOI: 10.4236/ijoc.2012.223043                

Abstract

A new biocidal agents fluorine substituted-3-thioxopyrimidine-5-carbonitriles (2-9) and/or the related fluorine substi- tuted pyrimido (4,5-d) pyrimidines (10-14) were synthesized by the cycloaddition of fluorinated β- arylidine malo- nonitriles (1a-c) followed by a nucleophilic attack against α,β-bifunctional reagents in different conditions. Structures of the fluorine targets were characterized by their elemental analysis and spectral data (UV, IR, ¹H NMR, ¹³C NMR and mass measurements) and further evaluated as photochemical probe for inhibition of Vitiligo, it was found that compounds 5, 9, 11 and 12 exhibited high potency over the investigated compounds.

Keywords

Synthesis; Fluoropyrimidines; Photochemical Probes

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	M. S. T. Makki, D. A. Bakhotmah and R. M. AbdelRahman, “Highly Efficient of Novel Fluorine Bearing Quinoline-4-Carboxylic Acid and the Related Compounds as Amylolytic Agents against Some Aspergillus Fungi,” International Journal of Organic Chemistry, Vol. 2, No. 1, 2012, pp. 49-53. doi:/10.4236/ijoc.2012.21009
[2]	R. M. Abdel-Rahman, M. S. T. Makki and W. A. Bawazir, “Synthesis of Some More Fluorine Heterocyclic Nitrogen Systems Derived from Sulfa-Drugs as Photochemical Probe Agents for Inhibition of Vitiligo Disease-Part I,” E-Journal of Chemistry, Vol. 8, No. 1, 2011, pp. 404-414.
[3]	R. M. Abdel-Rahman, M. S. T. Makki and W. A. Bawazir, “Synthesis of Some More Fluorine Heterocyclic Nitrogen Systems Derived from Sulfa-Drugs as Photochemical Probe Agents for inhibition of Vitiligo Disease-Part II,” E-Journal of Chemistry, Vol. 7, No. S1, 2010, pp. S93-S101.
[4]	D. J. Wang, L. Fan, C. Y. Zheng and Z. D. Fang, “Synthesis and Antimicrobial Activity of Some New Fluorinated 1H-Pyrazoles,” Journal of Fluorine Chemistry, Vol. 131, No. 5, 2010, pp. 584-586. doi:/10.1016/j.jfluchem.2010.01.005
[5]	R. Fillen and R. Saha, “Fluorine in Medicinal Chemistry: A Century of Progress and a 60-Year Retrospective of Selected Highlights Future,” Journal of Medicinal Chemistry, Vol. 1, No. 5, 2009, pp. 777-791.
[6]	G. Sandford, “Elemental Fluorine in Organic Chemistry (1997-2006),” Journal of Fluorine Chemistry, Vol. 128, No. 2, 2007, pp. 90-104. doi:/10.1016/j.jfluchem.2006.10.019
[7]	C. Isanbor and D. OHagan, “Fluorine in Medicinal Che istry: A Review of Anticancer Agents,” Journal of Flrine Chemistry, Vol. 127, No. 3, 2006, pp. 303-319. doi:/10.1016/j.jfluchem.2006.01.011
[8]	B. E. Smart, “Fluorine Substituent Effect (on Bioactivity) A-Review,” Journal of Fluorine Chemistry, Vol. 109, No. 1, 2001, pp. 3-11. doi:/10.1016/S0022-1139(01)00375-X
[9]	S. Liu, X. Qian, G. Song, J. Chem and W. Chen, “Fluorine Containing Heterocyclic Compounds: Synthesis of 6-Substituted-2-substitutedaryl-1,2,4-triazolo[5,1-b][1,3,5]-thiadiazin-7-one Derivatives,” Journal of Fluorine Chemistry, Vol. 105, No. 1, 2000, pp. 111-115. doi:/10.1016/S0022-1139(00)00287-6
[10]	R. M. Abdel-Rahman, “Synthesis and Chemistry of Fluorine Containing Bioactive 1,2,4-Triazines—An Overview,” Pharmazie, Vol. 54, No. 11, 1999, pp. 791-803.
[11]	A. T. Ramadan, R. M. Abdel-Rahman and M. Seada, “Studies on Complexes of Cu(II), Ni(II), Co(II) and Ln(II) with 3-(α-Benzoyl)benzylidene Hydrazino-5,6-diphen-yl-1,2,4-triazine,” Asian Journal of Chemistry, Vol. 4, 1992, pp. 569-575.
[12]	A. T. Ramadan, R. M. Abdel-Rahman, M. A. El-Behairy, A. I. Ismail and M. M. Mohamud, “Thermodynamics of Coplexation of Transition and Lanthanide Ions by 3-(α-Car-boxy-methylamino)benzylidene Hydrazino-5,6-diphenyl-1,2, 4-triazine,” Thermochimica Acta, 1993, pp. 222-291.
[13]	F. M. Foss, Best Practice & Research Clinical Haematology, Vol. 17, 2004, pp. 573-584.
[14]	E. K. Rowinsky, “Signal Events: Cell Signal Transduction and Its Inhibition in Cancer,” Oncologist, Vol. 8, No. Supplement 3, 2003, pp. 5-17. doi:/10.1634/theoncologist.8-suppl_3-5
[15]	G. Cockerill and K. E. Lackey, Current Topics in Medicinal Chemistry, Vol. 2, 2002, pp. 1001-1010.
[16]	V. Aparna, G. Rambabu, S. K. Panigrahi, J. A. R. P. Sharma and G. R. Desiraju, Journal of Chemical Information and Modeling, Vol. 45, 2005, pp. 725-738.
[17]	S. Emanuel, R. H. Gruninger, A. F. Pasquera, P. J. Connoly, J. A. Seamon, S. Hazel, R. Tominovich, B. Hollister, C. Napier, M. R. D’Andrea, M. Reuman, G. Bignan, R. Tuman, D. Johnson, D. Moffati, M. Batchelor, A. Foley, J. O. Connel, R. Allen, M. Perry, L. Jolliffe and S. A. Middleton, “A Vascular Endothelial Growth Factor Receptor-2 Kinase Inhibitor Potentiates the Activity of the Conventional Chemotherapeutic Agents Paclitaxel and Doxorubicin in Tumor Xenograft Models,” Molecular Pharmacology, Vol. 66, No
[18]	R. M. Fikry, “Synthesis of Some Pyrimidine and Condensed Derivatives,” Indian Journal of Heterocyclic Chemistry, Vol. 4, 1995, pp. 265-268.
[19]	R. M. Abdel-Rahman, “Chemoselective Heterocyclization and Pharmacological Activities of New Heterocycles—A Review Part V-Synthesis of Biocidal 4-Thiazolidinones Derivatives,” Bollettino Chimico Farmaceutico, Vol. 140, No. 6, 2001, pp. 401-410.
[20]	R. M. Abdel-Rahman and M. S. Abdel-Malik, “Synthesis of Some New 3,6-Diketoaryl-1,2,4-triazin-5-ones and Their Effects on Amylolytic Activity of Some Fungi,” Pakistan Journal of Science and Industrial Research, Vol. 33, 1990, pp. 142-147.
[21]	R. M. Abdel-Rahman, “Synthesis and Antihuman Immune Virus Activity of Some New Fluorine Containing Substituted 3-Thioxo-1,2,4-triazin-5-ones,” Farmaco, Vol. 46, No. 2, 1991, pp. 379-385
[22]	R. M. Abdel-Rahman, “Synthesis of Some New Fluorine Bearing Trisubstituted 3-Thioxo-1,2,4-triazin-5-one as Potential Cancer Agents, Farmaco, 1991, Vol. 47, No.3, pp. 319-324
[23]	E. De Clercq, “New Developments in Anti HIV Chemotherapy,” Biochimica et Biophysica Acta, Vol. 1587, No. 2-3, 2002, pp. 258-275. doi:/10.1016/S0925-4439(02)00089-3
[24]	W. R. Abdel-Monem and R. M. Abdel-Rahman, “Synthesis of 3-Heteroaryl-6,7-diphenyl-1,2,4-triazo-lo[4, 3-b] [1,2,4]tria-zines and Their Biological Activities,” International Journal of Chemistry, Vol. 16, No. 1, 2006, pp. 1-14.
[25]	R. M. Abdel-Rahman and W. R. Abdel-Monem, “Chemical Reactivity of 3-Hydrazino-5,6-diphenyl-1,2,4-triazine towards ?Acceptors Activated Carbonitriles,” Indian Journal of Chemistry, Vol. 46B, No. 5, 2007, pp. 838-846.
[26]	T. E. Ali, “Synthesis of Some Novel Pyrazolo[3,4b]pyridine and Pyrazolo[3,4-d]pyrimidine Derivatives Bearing 5,6-Diphenyl-1,2,4-triazine Moiety as Potential Antimicrobial Agents,” European Journal of Medicinal Chemistry, Vol. 44, No. 11, 2009, pp. 4385-4392.
[27]	A. L. Barry and C. Thornsberry, “In Susceptibility Testing Diffusion Tests Procedure,” American Society for Microbiology, Washington, 1981.
[28]	M. J. Weinstein and G. H. Nagman, “In Antibiotics,” Elsevier Scientific Publishing Company, Amesterdam, 1987.