[en] A series of novel 3,4-dihydropyrimidin-2(1H)-ones bearing urea, thiourea, and sulfonylurea moieties were synthesized and pharmacologically evaluated as vasodilator agents. The most interesting vasodilators were the thiourea derivatives 6a and 6b and the urea derivatives 6f-6i and 7f-7h, although the ureas were relatively more active than thioureas. Twenty-fold more active than diazoxide, the urea 6g was the most potent vasodilator (EC 50 = 0.983 ± 0.061 μmol/L) and proved to act as a voltage-gated calcium channel blocker. The lack of activity of sulfonylureas, 6k and 7j, could be attributed to their partial ionization at the physiological pH because of their acidic character. It should be interesting to investigate a larger number of compounds, including N-methylated sulfonylureas, to increase the vasodilator activity and to explore other biological models.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Habila, Tahir; Department of Chemistry, Laboratory of Phytochemistry and Pharmacology, University of Mohamed Seddik Benyahia, Jijel, Algeria ; Laboratory of Medicinal Chemistry, Center for Interdisciplinary Research on Medicines (CIRM), University of Liege, Liège, Belgium
Belghobsi, Mebrouk; Department of Chemistry, Laboratory of Phytochemistry and Pharmacology, University of Mohamed Seddik Benyahia, Jijel, Algeria
Stiti, Mohamed-Zakaria; Department of Chemistry, Laboratory of Phytochemistry and Pharmacology, University of Mohamed Seddik Benyahia, Jijel, Algeria ; Laboratory of Medicinal Chemistry, Center for Interdisciplinary Research on Medicines (CIRM), University of Liege, Liège, Belgium
Goffin, Eric ; Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
De Tullio, Pascal ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Faury, Gilles; Laboratory Cardiovascular and Respiratory Physiopathology (HP2), INSERM U1042, University of Grenoble-Alpes, La Tronche, France
Pirotte, Bernard ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Khelili, Smail; Department of Chemistry, Laboratory of Phytochemistry and Pharmacology, University of Mohamed Seddik Benyahia, Jijel, Algeria
Language :
English
Title :
Synthesis and vasodilator activity of 3,4-dihydropyrimidin-2(1H)-ones bearing urea, thiourea, and sulfonylurea moieties
This work was supported by the Algerian Ministry of Higher Education and Scientific Research, Laboratory of Phytochemistry and Pharmacology (University of Mohamed Seddik Ben Yahia, Jijel), Laboratory of Medicinal chemistry (University of Liège, Belgium), and HP2 laboratory (Grenoble-Alpes university-France). The authors gratefully acknowledge the technical assistance of Stéphane Counerotte, Sandrine Cachot, Bouraoui Hadia, and Aibech Riad.
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Bibliography
Grossman E. Messerli F. H. Prog. Cardiovasc. Dis. 2006, 49 (1), 16. 10.1016/j.pcad.2006.06.002.
Gupta S. P. Veerman A. Bagaria P. Mol. Diversity 2004, 8 (4), 357. 10.1023/B:MODI.0000047521.70687.52.
Kumar R. Kaur B. Bajaj V. J. Pharmacol. Pharmacother. 2013, 4 (1), 64. 10.4103/0976-500X.107688.
Marvaniya H. M. Parikh P. K. Sen D. J. J. Appl. Pharm. Sci. 2011, 1 (5), 109.
Cho H. Ueda M. Shima K. Mizuno A. Hayashimatsu M. Ohnaka Y. Takeuchi Y. Hamaguchi M. Aisaka K. J. Med. Chem. 1989, 32 (10), 2399. 10.1021/jm00130a029.
Atwal K. S. Swanson B. N. Unger S. E. Floyd D. M. Moreland S. Hedberg A. O'Reilly B. C. J. Med. Chem. 1991, 34 (2), 806. 10.1021/jm00106a048.
Chikhale R. Thorat S. Pant A. Jadhav A. Thatipamula K. C. Bansode R. Bhargavi G. Karodia N. Rajasekharan M. V. Paradkar A. Khedekar P. Bioorg. Med. Chem. 2015, 23 (20), 6689. 10.1016/j.bmc.2015.09.009.
Ramachandran V. Arumugasamy K. Singh S. K. Edayadulla N. Ramesh P. Kamaraj S.-K. J. Chem. Biol. 2016, 9 (1), 31. 10.1007/s12154-015-0142-4.
Tale R. H. Rodge A. H. Hatnapure G. D. Keche A. P. Bioorg. Med. Chem. Lett. 2011, 21 (15), 4648. 10.1016/j.bmcl.2011.03.062.
Hurst E. W. Hull R. J. Med. Chem. 1960, 3 (2), 215. 10.1021/jm50015a002.
Prashantha Kumar B. R. Sankar G. Nasir Baig R. B. Chandrashekaran S. Eur. J. Med. Chem. 2009, 44 (10), 4192. 10.1016/j.ejmech.2009.05.014.
Chhabria M. T. Bhatt H. G. Raval H. G. Oza P. M. Bioorg. Med. Chem. Lett. 2007, 17 (4), 1022. 10.1016/j.bmcl.2006.11.035.
Hughes T. V. Emanuel S. L. Beck A. K. Wetter S. K. Connolly P. J. Karnachi P. Reuman M. Seraj J. Fuentes-Pesquera A. R. Gruninger R. H. Middleton S. A. Lin R. Davis J. M. Moffat D. F. C. Bioorg. Med. Chem. Lett. 2007, 17 (12), 3266. 10.1016/j.bmcl.2007.04.021.
Sayle K. L. Bentley J. Boyle F. T. Calvert A. H. Cheng Y. Curtin N. J. Endicott J. A. Golding B. T. Hardcastle I. R. Jewsbury P. Mesguiche V. Newell D. R. Noble M. E. M. Parsons R. J. Pratt D. J. Wang L. Z. Griffin R. J. Bioorg. Med. Chem. Lett. 2003, 13 (18), 3079. 10.1016/S0960-894X(03)00651-6.
Pastor A. Alajarin R. Vaquero J. J. Alvarez-Builla J. de Casa-Juana M. F. Sunkel C. Priego J. G. Fonseca I. Sanz-Aparicio J. Tetrahedron 1994, 50 (27), 8085. 10.1016/S0040-4020(01)85291-1.
Youssouf M. S. Kaiser P. Singh G. D. Singh S. Bani S. Gupta V. K. Satti N. K. Suri K. A. Johri R. K. Int. Immunopharmacol. 2008, 8 (7), 1049. 10.1016/j.intimp.2008.03.015.
Gasse C. Douguet D. Huteau V. Marchal G. Munier-Lehmann H. Pochet S. Bioorg. Med. Chem. 2008, 16 (11), 6075. 10.1016/j.bmc.2008.04.045.
Patil A. D. Kumar N. V. Kokke W. C. Bean M. F. Freyer A. J. De Brosse C. Shing M. Truneh A. Faulkner D. J. Carte B. Breen A. L. Hertzberg R. P. Johnson R. K. Westley J. W. Potts C. M. B. J. Org. Chem. 1995, 60, 1182. 10.1021/jo00110a021.
Kim J. Ok T. Park C. So W. Jo M. Kim Y. Seo M. Lee D. Jo S. Ko Y. Choi I. Park Y. Yoon J. Ju M. K. Ahn J. Kim J. Han S.-J. Kim T.-H. Cechetto J. Nam J. Liuzzi M. Sommer P. No Z. Bioorg. Med. Chem. Lett. 2012, 22, 2522. 10.1016/j.bmcl.2012.01.133.
Akika F.-Z. Kihal N. Habila T. Avramova I. Suzer S. Pirotte B. Khelili S. Bull. Korean Chem. Soc. 2013, 34 (5), 1445. 10.5012/bkcs.2013.34.5.1445.
Bouider N. Fhayli W. Ghandour Z. Boyer M. Harrouche K. Florence X. Pirotte B. Lebrun P. Faury G. Khelili S. Bioorg. Med. Chem. 2015, 23 (8), 1735. 10.1016/j.bmc.2015.02.043.
Bouhedja M. Peres B. Fhayli W. Ghandour Z. Boumendjel A. Faury G. Khelili S. Eur. J. Med. Chem. 2018, 144, 774. 10.1016/j.ejmech.2017.12.071.
Harrouche K. Renard J.-F. Bouider N. de Tullio P. Goffin E. Lebrun P. Faury G. Pirotte B. Khelili S. Eur. J. Med. Chem. 2016, 115, 352. 10.1016/j.ejmech.2016.03.028.
Hamilton T. C. Weir S. W. Weston A. H. Br. J. Pharmacol. 1986, 88 (1), 103. 10.1111/j.1476-5381.1986.tb09476.x.
Robertson D. W. Steinberg M. I. J. Med. Chem. 1990, 33 (6), 1529. 10.1021/jm00168a001.
Pirotte B. Ouedraogo R. De Tullio P. Khelili S. Somers F. Boverie S. Dupont L. Fontaine J. Damas J. Lebrun P. J. Med. Chem. 2000, 43 (8), 1456. 10.1021/jm991069o.
Rajack A. Yuvaraju K. Praveen C. Murthy Y. L. N. J. Mol. Catal. A: Chem. 2013, 370, 197. 10.1016/j.molcata.2013.01.003.
Stiasni N. Kappe C. O. ARKIVOC 2002, 2002 (8), 71. 10.3998/ark.5550190.0003.809.
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